Linker ID	LIN0YRUBS
Linker Name	Mal-PEG8-Val-Ala-PABC
Linker Type	Cathepsin-cleavable linker
Antibody-Linker Relation	Cleavable
Structure
	3D MOL			2D MOL
Formula	C41H65N5O15
Isosmiles	C[C@@H](C(=O)NC1=CC=C(C=C1)CO)NC(=O)[C@H](C(C)C)NC(=O)CCOCCOCCOCCOCCOCCOCCOCCOCCNC(=O)CCN2C(=O)C=CC2=O
PubChem CID	145157750
InChI	InChI=1S/C41H65N5O15/c1-31(2)39(41(53)43-32(3)40(52)44-34-6-4-33(30-47)5-7-34)45-36(49)11-14-54-16-18-56-20-22-58-24-26-60-28-29-61-27-25-59-23-21-57-19-17-55-15-12-42-35(48)10-13-46-37(50)8-9-38(46)51/h4-9,31-32,39,47H,10-30H2,1-3H3,(H,42,48)(H,43,53)(H,44,52)(H,45,49)/t32-,39-/m0/s1
InChIKey	YJYDWLGCCNOUSJ-GSSDHLSPSA-N
IUPAC Name	(2S)-2-[3-[2-[2-[2-[2-[2-[2-[2-[2-[3-(2,5-dioxopyrrol-1-yl)propanoylamino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]propanoylamino]-N-[(2S)-1-[4-(hydroxymethyl)anilino]-1-oxopropan-2-yl]-3-methylbutanamide
Pharmaceutical Properties	Molecule Weight		868	Polar area		248
	Complexity		1280	xlogp Value		-2.1
	Heavy Count		61	Rot Bonds		37
	Hbond acc		15	Hbond Donor		5

Experiment 1 Reporting the Activity Date of This ADC					[1]
Efficacy Data	Objective Response Rate (ORR)	48.28%
Patients Enrolled	Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more multiagent systemic treatments, who had measurable disease and Eastern Cooperative Oncology Group performance status 0-2.
Administration Dosage	Intravenously on day 1 of each 21-day cycle, at 150 ug/kg for two cycles, then 75 ug/kg thereafter, for up to 1 year or until disease relapse or progression, unacceptable toxicity, death, major protocol deviation, pregnancy, or patient, investigator, or sponsor decision.
Related Clinical Trial
NCT Number	NCT03589469	Clinical Status	Phase 2
Clinical Description	A phase 2 open-label single-arm study to evaluate the efficacy and safety of loncastuximab tesirine in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL) (LOTIS-2).
Primary Endpoint	Overall response rate assessed by central review. 70 of 145 patients had complete or partial response (overall response rate 48.28% [95% CI 39.9-56.7]); 35 had complete response and 35 had partial response.
Other Endpoint	Median time to first response (complete response or partial response) was 41.00 days (IQR 38.00-44.00). Median duration of response was 10.30 months (95% CI 6.9-not estimable); 13.40 months (10.30-not estimable) for patients with complete response and 5.70 months (1.70-not estimable) for patients with partial response. The probability of responders maintaining responses for 9 months or longer was 64.0%. Median progressionfree survival was 4.90 months (95% CI 2.90-8.30), median overall survival was 9.90 months (6.70-11.50), and median relapse-free survival was 13.40 months (10.30-not estimable).    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[2]
Efficacy Data	Objective Response Rate (ORR)	59.40%
Patients Enrolled	R/R B-cell non Hodgkin lymphoma (NHL); had failed or were intolerant to established therapies, or for whom no other established treatment options were available.
Administration Dosage	5 to 200 ug/kg; intravenously over 1 hour, once every 3 weeks (one cycle) by a 3+3 dose-escalation design.
Related Clinical Trial
NCT Number	NCT02669017	Clinical Status	Phase 1
Clinical Description	A phase 1 dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-402 in patients with relapsed or refractory b-cell lineage non Hodgkin lymphoma (B-NHL).
Primary Endpoint	The MTD was not established during the trial due to the low level of DLTs, 150 ug/kg dose for expansion and phase 2.
Other Endpoint	For loncastuximab tesirine 120 ug/kg,Median Progression-Free Survival (mPFS)=4.80 months.The median PFS OS=11.60 months.
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Complete Remission (CR)	26.70%
Patients Enrolled	Adults (age 18 years) with histologically confirmed relapsed/refractory B-non Hodgkin lymphoma (World Health Organization 2008 classification18 ) who were intolerant to established therapy, for whom established therapy had failed, or for whom no other treatment options were available in the opinion of the investigator were eligible to participate.
Administration Dosage	3 + 3 dose escalation at 15 to 200 ug/kg and dose expansion at 120 and 150 ug/kg; IV infusion over 60 minutes once every 3 weeks (day 1 of each 21-day cycle).
Related Clinical Trial
NCT Number	NCT02669017	Clinical Status	Phase 1
Clinical Description	A phase 1 dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-402 in patients with relapsed or refractory B-cell lineage non Hodgkin lymphoma (B-NHL).
Primary Endpoint	The recommended dose of loncastuximab tesirine for Phase 2 is 150 ug/kg Q3W for 2 doses followed by 75 ug/kg Q3W for subsequent doses. The 150 ug/kg dose was selected as a dose with encouraging responses but lower frequency of AEs than observed with the 200 u/kg dose. Overall response rate (ORR) in evaluable patients was 45.60%, including 26.70% complete responses (CR). Median PFS was 3.10 months (95% CI 2.70-4.20) in all patients with B-NHL, 2.8 months (95% CI 1.90-3.80) in patients with DLBCL, 4.80 months (95% CI 1.10-7.80) in patients with MCL, and could not be determined in those with FL due to the low number of events. Median OS was 8.3 months (95% CI 6.70-10.70) in all patients with B-NHL, 7.5 months (95% CI 6.00-9.80) in patients with DLBCL, and was not reached in patients with MCL or FL due to low number of events.    Click to Show/Hide
Other Endpoint	PK exposure similarity between loncastuximab tesirine total antibody and PBD-conjugated antibody indicated good stability in serum.Accumulation by Cycle 2 for patients on a Q6W dosing regimen was lower than that of those on Q3W dosing: mean accumulation of 1.22 and 1.33 for PBD-conjugated antibody and total antibody on Q6W regimens compared with 1.72 and 1.74 on Q3W regimens. There was substantial variability in PK exposure and PK parameters assessed for PBD-conjugated antibody, total antibody, and SG3199.    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[4]
Efficacy Data	Complete Remission (CR)	40.20%
Patients Enrolled	R/R B-acute lymphocytic leukemia (ALL) for standard therapies had failed, intolerant to standard therapies, or no other treatment options were available, in the opinion of the investigator, were eligible for the study, other key inclusion criteria included Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
Administration Dosage	15 to 150 ug/kg once every 3 weeks (Q3W) or 50 ug/kg IV weekly.
Related Clinical Trial
NCT Number	NCT02669264	Clinical Status	Phase 1
Clinical Description	A phase 1, open-label, adaptive dose-escalation, multicenter study to evaluate the tolerability, safety, pharmacokinetics, and anti-tumor activity of ADCT-402 in patients with relapsed or refractory B-cell lineage acute lymphoblastic leukemia (B-ALL).
Primary Endpoint	Part II (dose expansion portion) utilized the doses of 120 and 150 ug/kg, selected based on antitumor activity and tolerability seen during part I. The overall response rate (ORR) in patients with DLBCL, mantle cell lymphoma, and follicular lymphoma was 42.30%, 46.70%, and 78.60%, respectively.
Other Endpoint	The median progression-free survival (PFS) was 3.10 months in all patients with B-NHL and 2.80 months in patients with DLBCL, whereas the median OS was 8.30 months in all patients and 7.50 months in patients with DLBCL.
Experiment 5 Reporting the Activity Date of This ADC					[5]
Efficacy Data	Complete Remission (CR)	46.16%

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	stable disease (SD)	21%
Patients Enrolled	Eligible participants had DLL3-high (≥75% tumor staining) advanced SCLC progressing after first-line platinum therapy (ECOG 0-1, measurable disease), excluding those with recent cardiovascular events, leptomeningeal metastases, >1 prior regimen, active infections, other malignancies within 2 years, or prior topoisomerase I inhibitors.
Administration Dosage	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Related Clinical Trial
NCT Number	NCT03061812	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Primary Endpoint	The primary endpoint evaluated overall survival (OS) from randomization to death (Kaplan-Meier method) with median follow-up of 20-20.6 months across treatment arms, censoring at last documented alive date or study termination (12 Feb 2020), with survival data collected every 6 weeks post-treatment.
Other Endpoint	Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) per RECIST v1.1 via CT scans (assessed every 6-9 weeks), plus EORTC QLQ-C15-PAL physical functioning score changes at Week 7 (0-100 scale), with median follow-up matching OS timeframe.
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	progressive disease (PD)	54%
Patients Enrolled	Eligible participants had DLL3-high (≥75% tumor staining) advanced SCLC progressing after first-line platinum therapy (ECOG 0-1, measurable disease), excluding those with recent cardiovascular events, leptomeningeal metastases, >1 prior regimen, active infections, other malignancies within 2 years, or prior topoisomerase I inhibitors.
Administration Dosage	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Related Clinical Trial
NCT Number	NCT03061812	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Primary Endpoint	The primary endpoint evaluated overall survival (OS) from randomization to death (Kaplan-Meier method) with median follow-up of 20-20.6 months across treatment arms, censoring at last documented alive date or study termination (12 Feb 2020), with survival data collected every 6 weeks post-treatment.
Other Endpoint	Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) per RECIST v1.1 via CT scans (assessed every 6-9 weeks), plus EORTC QLQ-C15-PAL physical functioning score changes at Week 7 (0-100 scale), with median follow-up matching OS timeframe.
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Partial Response (PR)	14%
Patients Enrolled	Eligible participants had DLL3-high (≥75% tumor staining) advanced SCLC progressing after first-line platinum therapy (ECOG 0-1, measurable disease), excluding those with recent cardiovascular events, leptomeningeal metastases, >1 prior regimen, active infections, other malignancies within 2 years, or prior topoisomerase I inhibitors.
Administration Dosage	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Related Clinical Trial
NCT Number	NCT03061812	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Primary Endpoint	The primary endpoint evaluated overall survival (OS) from randomization to death (Kaplan-Meier method) with median follow-up of 20-20.6 months across treatment arms, censoring at last documented alive date or study termination (12 Feb 2020), with survival data collected every 6 weeks post-treatment.
Other Endpoint	Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) per RECIST v1.1 via CT scans (assessed every 6-9 weeks), plus EORTC QLQ-C15-PAL physical functioning score changes at Week 7 (0-100 scale), with median follow-up matching OS timeframe.
Experiment 4 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Objective Response Rate (ORR)	15%
Patients Enrolled	Eligible participants had DLL3-high (≥75% tumor staining) advanced SCLC progressing after first-line platinum therapy (ECOG 0-1, measurable disease), excluding those with recent cardiovascular events, leptomeningeal metastases, >1 prior regimen, active infections, other malignancies within 2 years, or prior topoisomerase I inhibitors.
Administration Dosage	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Related Clinical Trial
NCT Number	NCT03061812	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Primary Endpoint	The primary endpoint evaluated overall survival (OS) from randomization to death (Kaplan-Meier method) with median follow-up of 20-20.6 months across treatment arms, censoring at last documented alive date or study termination (12 Feb 2020), with survival data collected every 6 weeks post-treatment.
Other Endpoint	Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) per RECIST v1.1 via CT scans (assessed every 6-9 weeks), plus EORTC QLQ-C15-PAL physical functioning score changes at Week 7 (0-100 scale), with median follow-up matching OS timeframe.
Experiment 5 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Complete response (CR)	0.30%
Patients Enrolled	Eligible participants had DLL3-high (≥75% tumor staining) advanced SCLC progressing after first-line platinum therapy (ECOG 0-1, measurable disease), excluding those with recent cardiovascular events, leptomeningeal metastases, >1 prior regimen, active infections, other malignancies within 2 years, or prior topoisomerase I inhibitors.
Administration Dosage	Rovalpituzumab tesirine IV administration (dosing based on actual body weight) on Day 1 of a 42-day cycle for 2 cycles, with up to 2 additional cycles permitted.
Related Clinical Trial
NCT Number	NCT03061812	Clinical Status	PHASE3
Clinical Description	A Randomized, Open-Label, Multicenter, Phase 3 Study of Rovalpituzumab Tesirine Compared With Topotecan for Subjects With Advanced or Metastatic DLL3high Small Cell Lung Cancer (SCLC) Who Have First Disease Progression During or Following Front-Line Platinum-Based Chemotherapy (TAHOE)
Primary Endpoint	The primary endpoint evaluated overall survival (OS) from randomization to death (Kaplan-Meier method) with median follow-up of 20-20.6 months across treatment arms, censoring at last documented alive date or study termination (12 Feb 2020), with survival data collected every 6 weeks post-treatment.
Other Endpoint	Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), and duration of response (DOR) per RECIST v1.1 via CT scans (assessed every 6-9 weeks), plus EORTC QLQ-C15-PAL physical functioning score changes at Week 7 (0-100 scale), with median follow-up matching OS timeframe.
Experiment 6 Reporting the Activity Date of This ADC					[7]
Patients Enrolled	Eligible patients had DLL3-expressing (≥1% tumor cells), progressive advanced solid tumors refractory to ≥1 prior therapy, ECOG 0-1, and adequate organ function. Key exclusions included active infections, recent cardiovascular events, prior PBD-based drugs, uncontrolled comorbidities, pregnancy/breastfeeding, or other malignancies within 3 years (except specified exceptions). CNS metastases required stability post-treatment.    Click to Show/Hide
Administration Dosage	Rovalpituzumab tesirine 0.2-0.4 mg/kg administered intravenously on Day 1 of each 6-week cycle. Dexamethasone 8 mg administered orally twice daily on Day -1, Day 1 (the day of dosing), and Day 2 of each 6-week cycle.
Related Clinical Trial
NCT Number	NCT02709889	Clinical Status	PHASE1|||PHASE2
Clinical Description	An Open-Label Study of Rovalpituzumab Tesirine in Subjects With Delta-Like Protein 3-Expressing Advanced Solid Tumors
Primary Endpoint	The study assessed treatment-emergent adverse events (TEAEs) across neuroendocrine (NEC) and non-NEC disease groups, including serious TEAEs and drug-related events leading to discontinuation/dose reduction, graded per NCI CTCAE v4.03 from first dose through 30 days post-treatment (mean 1 cycle, range 1-5 cycles).
Other Endpoint	Efficacy endpoints included objective response rate (ORR), clinical benefit rate (CBR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) assessed per RECIST v1.1 up to 35.2 months. Pharmacokinetic analysis measured rovalpituzumab tesirine serum concentrations during Cycle 1, with anti-therapeutic antibodies (ATA) evaluated at Day 1 and 42 days post-last dose.    Click to Show/Hide
Experiment 7 Reporting the Activity Date of This ADC					[8]
Patients Enrolled	Eligible participants must have previously received ≥1 rovalpituzumab tesirine dose in a parent study. Retreatment candidates (Arm A) required initial treatment tolerance, prior clinical benefit (stable disease or better), ≥12-week progression-free interval post-treatment, ECOG 0-1, adequate organ function, and stable CNS metastases if applicable. Exclusion criteria prohibited enrollment of subjects without prior rovalpituzumab tesirine study participation.    Click to Show/Hide
Administration Dosage	Rovalpituzumab tesirine (0.3 mg/kg or previously adjusted dose) administered intravenously once every 6 weeks beginning on Day 1 (day of dosing). Subjects will receive rovalpituzumab tesirine on Day 1 of each 6-week cycle, omitting every third cycle until disease progression or study drug discontinuation.
Related Clinical Trial
NCT Number	NCT03543358	Clinical Status	PHASE2
Clinical Description	A Multicenter, Long-Term, Rollover Extension Study of Rovalpituzumab Tesirine
Primary Endpoint	The study monitored treatment-emergent adverse events (TEAEs) and serious TEAEs in participants receiving rovalpituzumab tesirine treatment or retreatment from first dose until 70 days post-last dose (up to ~5 years), with investigator-assessed causality and severity grading per standard definitions.
Experiment 8 Reporting the Activity Date of This ADC					[9]
Patients Enrolled	Eligible participants must be ≥18 years with chemotherapy-naïve extensive-stage SCLC showing ≥75% DLL3 expression, ECOG 0-1, adequate organ function, and stable CNS metastases if present, excluding those with prior SCLC treatments, significant comorbidities, recent cardiovascular events, active infections, pregnancy, other malignancies within 3 years, or PBD-based drug exposure.    Click to Show/Hide
Administration Dosage	Rovalpituzumab Tesirine 0.3 mg/kg IV infusion; Rovalpituzumab Tesirine 0.3 mg/kg IV infusion followed by Cisplatin 80 mg/m2 and Etoposide 100 mg/m2 IV infusion.
Related Clinical Trial
NCT Number	NCT02819999	Clinical Status	PHASE1
Clinical Description	A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Primary Endpoint	The study evaluates dose-limiting toxicities (DLTs) within 21 days post-dose and treatment-emergent adverse events (TEAEs) through 30 days after treatment in Phase 1a, along with Grade >2 lab abnormalities and 4-year progression-free survival (PFS) as key safety endpoints for DLL3-expressing SCLC patients receiving rovalpituzumab tesirine monotherapy or combination therapy.    Click to Show/Hide
Other Endpoint	Phase 1b assesses efficacy outcomes including best overall response, duration of response, clinical benefit rate, and overall survival over 4 years, while monitoring pharmacokinetic parameters (Cmax, AUC, T1/2 etc.), anti-drug antibodies, TEAEs, vital signs, and ECOG performance status throughout the 4-year study period.
Experiment 9 Reporting the Activity Date of This ADC					[10]
Patients Enrolled	Eligible patients must have extensive-stage SCLC with ECOG 0-2 and adequate organ function, excluding those with significant cardiac abnormalities (QTcF >470/450ms, conduction defects, LVEF<0.30, arrhythmia history), active infections, pregnancy, prior PBD exposure, or hypersensitivity to study drug components.
Administration Dosage	0.3 mg/kg rovalpituzumab tesirine intravenously on Day 1 of every 6-week treatment cycle for 2 cycles omitting every third cycle
Related Clinical Trial
NCT Number	NCT02874664	Clinical Status	PHASE1
Clinical Description	An Intensive QT/QTc Study to Investigate the Effects of Rovalpituzumab Tesirine on Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer
Primary Endpoint	The primary endpoint evaluates QTcF interval changes from baseline over 12 weeks using Holter monitor-derived ECG parameters in patients treated with rovalpituzumab tesirine.
Other Endpoint	Secondary endpoints include 12-week ECG parameter changes (RR, PR, QRS, waveform), QTcF-plasma concentration correlation, arrhythmia events stratified by QTcF changes, safety monitoring through 30 days post-treatment, efficacy outcomes (ORR, DOR, PFS, OS, CBR) assessed up to 24 months, and pharmacokinetic analysis (Cmax, AUC) during treatment cycles.    Click to Show/Hide
Experiment 10 Reporting the Activity Date of This ADC					[11]
Patients Enrolled	Inclusion requires ineligibility for standard Rovalpituzumab Tesirine trials, with potential case-by-case pediatric enrollment consideration, while no exclusion criteria are established for participation.
Related Clinical Trial
NCT Number	NCT03503890	Clinical Status	N.A.
Clinical Description	Expanded Access to Rovalpituzumab Tesirine
Experiment 11 Reporting the Activity Date of This ADC					[12]
Patients Enrolled	Eligible participants were &ge;18 years with progressive SCLC after 1-2 prior platinum regimens (ECOG 0-1), adequate organ function, controlled CNS metastases, and proper contraception, excluding those with active CNS disease, uncontrolled cardiac conditions, recent anticancer therapies (<14-21 days), QTcF >450/470ms, HIV/Hepatitis, or hypersensitivity to drug components.    Click to Show/Hide
Administration Dosage	Rovalpituzumab tesirine will be administered as a single agent, at increasing dose levels as permitted based on real-time assessment of safety and tolerability, intravenously over 30 minutes. Doses will be repeated on Day 1 of each 21-day or 42-day cycle until either unacceptable toxicity or evidence of disease progression occurs.
Related Clinical Trial
NCT Number	NCT01901653	Clinical Status	PHASE1|||PHASE2
Clinical Description	Phase I/II Open Label Dose Escalation Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of SC16LD6.5 as a Single Agent in Patients With Recurrent Small Cell Lung Cancer
Primary Endpoint	The primary endpoint assessed the Maximum Tolerated Dose (MTD) of Rovalpituzumab Tesirine during dose escalation (Phase 1a), defined as the highest dose below which ≥2 of 3-6 subjects experienced dose-limiting toxicities within 21-42 days across tested doses (0.05-0.8 mg/kg every 21/42 days).
Other Endpoint	Secondary endpoints included efficacy measures (ORR, DOR, CBR, PFS, OS) evaluated per RECIST v1.1 by investigators and independent review, with median observation periods of 4-7 months (up to 14.6 months), plus pharmacokinetic analysis of ADC Cmax and AUC during treatment cycles.
Experiment 12 Reporting the Activity Date of This ADC					[13]
Patients Enrolled	Eligible participants were adults with DLL3-positive (&ge;1% tumor staining) SCLC progressing after &ge;2 prior regimens (including platinum), having measurable disease, ECOG 0-1, and adequate organ function, while excluding those with active infections, recent cardiovascular events, uncontrolled comorbidities, concurrent corticosteroids >20mg/day, other malignancies within 3 years, or prior PBD exposure unless undergoing protocol-specified retreatment.    Click to Show/Hide
Administration Dosage	0.3 mg/kg rovalpituzumab tesirine administered intravenously on Day 1 of each 42-day cycle (every 6 weeks; Q6W) for 2 cycles. An additional 2 cycles of rovalpituzumab tesirine (retreatment) was permitted for eligible participants.
Related Clinical Trial
NCT Number	NCT02674568	Clinical Status	PHASE2
Clinical Description	An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY)
Primary Endpoint	The primary efficacy endpoints evaluated objective response rate (confirmed CR/PR per RECIST v1.1) and overall survival over a mean follow-up of 29 weeks (up to 122.4 weeks), with tumor assessments conducted by both investigators and independent review committees.
Other Endpoint	Secondary endpoints included overall response rate (unconfirmed CR/PR), duration of response, progression-free survival, clinical benefit rate (CR/PR/SD≥42 days), pharmacokinetic measurements, immunogenicity (ATA), and treatment-emergent adverse events during initial treatment, all analyzed over the same 122.4-week maximum observation period.
Experiment 13 Reporting the Activity Date of This ADC					[14]
Patients Enrolled	Eligible participants were adults with extensive-stage SCLC progressing after &ge;1 platinum regimen (ECOG 0-1), excluding those with active autoimmune diseases or prior immuno-oncology/PBD-based therapy, with adequate organ function required for enrollment.
Administration Dosage	Participants will receive 2 doses of 0.3 mg/kg rovalpituzumab tesirine by intravenous (IV) infusion 6 weeks apart (Day 1 of Cycles 1 and 3), and 2 doses of 360 mg nivolumab IV 3 weeks apart beginning on Cycle 2 (Day 1 of Cycles 2 and 3).
Related Clinical Trial
NCT Number	NCT03026166	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Phase 1/2 Study on the Safety of Rovalpituzumab Tesirine Administered in Combination With Nivolumab or Nivolumab and Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer
Primary Endpoint	The primary safety endpoints evaluated dose-limiting toxicities (DLTs) over 12 weeks per NCI CTCAE v4.03 criteria, including Grade 4 hematologic events and clinically significant Grade 3/4 non-hematologic AEs, with adverse event monitoring continuing until 100 days post-treatment (median treatment duration 53-65 days).
Experiment 14 Reporting the Activity Date of This ADC					[15]
Patients Enrolled	Eligible participants had ED-SCLC with ongoing benefit (SD/PR/CR) after 4 platinum cycles (randomized 3-9 weeks post-cycle 4), ECOG 0-1, controlled CNS metastases, and tumor tissue for DLL3 testing, excluding prior non-platinum therapies, recent radiotherapy (except PCI/palliative), or PBD-based drug exposure.
Administration Dosage	Rovalpituzumab tesirine/dexamethasone every 6 weeks (q6 wk); omitting every third cycle.
Related Clinical Trial
NCT Number	NCT03033511	Clinical Status	PHASE3
Clinical Description	A Randomized, Double-Blind, Placebo-Controlled Phase 3 Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First-Line Platinum-Based Chemotherapy in Subjects With Extensive Stage Small Cell Lung Cancer (MERU)
Primary Endpoint	The primary endpoint assessed overall survival (OS) in DLL3-high extensive-stage SCLC patients, defined as months from randomization to death (Kaplan-Meier method), with median study duration of 11.9 months until death/loss to follow-up/study termination.
Other Endpoint	Secondary analyses included OS in all randomized participants (same methodology) and EORTC QLQ-C30 physical functioning domain changes from baseline (0-100 scale, higher=better QoL), measured every 6 weeks until Week 78.
Experiment 15 Reporting the Activity Date of This ADC					[16]
Patients Enrolled	Eligible participants had advanced SCLC progressing after &ge;2 prior regimens (including platinum), ECOG 0-1, and adequate organ function, while excluding those with prior PBD-based drug exposure to ensure treatment-naive status for the experimental therapy.
Administration Dosage	Part A Dose Escalation: Rovalpituzumab tesirine intravenous (IV) (various doses and dose regimens) on Day 1 of each 6-week cycle; Part B Dose Expansion: Rovalpituzumab tesirine dosed at regimen (s) previously demonstrated in Part A to not to exceed the maximum tolerated dose (MTD).
Related Clinical Trial
NCT Number	NCT03086239	Clinical Status	PHASE1
Clinical Description	An Open-Label Study on the Safety and Tolerability of Rovalpituzumab Tesirine in Japanese Patients With Advanced, Recurrent Small Cell Lung Cancer
Primary Endpoint	The primary safety endpoint assessed dose-limiting toxicities (DLTs) during the first 3 weeks of Cycle 1 using NCI CTCAE v4.03 criteria, evaluating hematologic and non-hematologic adverse events for toxicity thresholds.
Other Endpoint	Key efficacy measures included objective response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) per RECIST v1.1, with assessments conducted from first dose through minimum 18-week follow-up (42 days post-treatment) and extended OS monitoring up to 24 months.
Experiment 16 Reporting the Activity Date of This ADC					[17]
Patients Enrolled	Eligible participants had DLL3-expressing SCLC progressing after &ge;2 prior regimens (including platinum), ECOG 0-1, measurable disease, and stable CNS metastases if present, while excluding those with recent cardiovascular events, active infections, other malignancies within 3 years, prior PBD exposure, or hypersensitivity to study drug components.    Click to Show/Hide
Administration Dosage	Rovalpituzumab tesirine 0.3 mg/kg administered intravenously on Day 1 of each 6-week cycle plus oral dexamethasone 8 mg twice daily on Day -1, Day 1, and Day 2 of 6-week each cycle.
Related Clinical Trial
NCT Number	NCT03334487	Clinical Status	PHASE3
Clinical Description	Open-Label, Single Arm, Phase 3b Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory DLL3 Expressing Small Cell Lung Cancer
Primary Endpoint	The primary safety outcome evaluated high-grade (≥Grade 3) treatment-emergent adverse events (TEAEs) over approximately 32 months using NCI CTCAE v4.03 criteria, with severity assessments conducted at each study visit to monitor treatment-related toxicities.
Other Endpoint	Key efficacy measures included progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR) per RECIST v1.1, along with quality-of-life assessments via EORTC QLQ-C15-PAL and QLQ-LC13 questionnaires, all monitored over approximately 32 months to evaluate treatment impact on disease progression and patient-reported outcomes.    Click to Show/Hide
Experiment 17 Reporting the Activity Date of This ADC					[18]
Patients Enrolled	Key eligibility requires ECOG 0-2 (0-1 for combinations), adequate organ function, and disease-specific prior therapy profiles. Notable exclusions include: recent immunosuppressants (14-day washout), active autoimmune/inflammatory conditions, uncontrolled CNS metastases, CYP3A modifiers for venetoclax arm, and prior PBD exposure for SCLC cohort. The study incorporates rigorous safety monitoring through 90-day follow-up after last dose (up to 24 months total), with special attention to immune-related AE risks and drug-specific toxicities.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT03000257	Clinical Status	PHASE1
Clinical Description	A Multicenter, Phase 1, Open-Label, Dose-Escalation Study of ABBV-181 as Monotherapy and in Combination With Another Anti-Cancer Therapy in Subjects With Advanced Solid Tumors
Primary Endpoint	This multi-part phase 1 study evaluates budigalimab (anti-PD-1) across three treatment settings: monotherapy dose escalation (Part 1), combination with rovalpituzumab tesirine in SCLC (Part 2), and combination with venetoclax in NSCLC (Part 3). Primary objectives include determining MTD/RP2D through DLT evaluation (≤33% incidence threshold), characterizing PK parameters (t1/2, Cmax, Tmax, AUC), and assessing safety profiles over 6-month dose-finding periods. Pharmacokinetic sampling continues for 12 weeks post-dose.    Click to Show/Hide
Other Endpoint	Secondary objectives assess antitumor activity through RECIST v1.1-defined endpoints (ORR, CBR, PFS, DOR) with 30-day post-treatment follow-up. Combination arms include additional PK analyses for co-administered agents (rovalpituzumab tesirine/venetoclax). The study employs a traditional 3+3 design for dose escalation, with expansion cohorts requiring measurable disease and specific prior therapy exposure (e.g., PD-1/PD-L1 naïve status for SCLC cohort, 1 prior PD-1/L1-containing regimen for NSCLC cohort).    Click to Show/Hide
Experiment 18 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Objective Response Rate (ORR)	10%
Patients Enrolled	Extensive-stage small-cell lung cancer (ES-SCLC) who had completed four cycles of front-line platinum-based chemotherapy (cisplatin or carboplatin with etoposide or irinotecan) at least 3 weeks but not more than 9 weeks before randomization and had stable disease, PR, or CR per RECIST v.1.1.
Administration Dosage	0.30 mg/kg intravenous Rova-T on day 1 of each 6-week cycle, omitting every third cycle.
Related Clinical Trial
NCT Number	NCT03033511	Clinical Status	Phase 3
Clinical Description	A randomized, double-blind, placebo-controlled phase 3 study of rovalpituzumab tesirine as maintenance therapy following first-line platinum-based chemotherapy in subjects with extensive stage small cell lung cancer (MERU).
Primary Endpoint	Median age of all randomized patients (N=748) was 64 years; 78.00% had TNM stage IV disease. At futility analysis of the subset with DLL3-high tumors, the hazard ratio for OS was 1.07 (95% confidence interval: 0.84-1.36) favoring the placebo arm,with median OS of 8.50 and 9.80 months in the Rova-T and placebo arms,respectively; futility criteria were met. Rova-T significantly improved PFS versus placebo by investigator assessment (4.00 versus 1.40 mo,hazard ratio=0.48, p < 0.001).    Click to Show/Hide
Experiment 19 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Objective Response Rate (ORR)	12.40 14.30 13.20 %
Patients Enrolled	Advanced stage DLL3-positive small-cell lung cancer (SCLC).
Administration Dosage	0.30 mg/kg Rova-T intravenously infused over 30 minutes once every 6 weeks for two cycles.
Related Clinical Trial
NCT Number	NCT02674568	Clinical Status	Phase 2
Clinical Description	An Open-label, Single-Arm, Phase 2 Study Evaluating the Efficacy, Safety and Pharmacokinetics of Rovalpituzumab Tesirine (SC16LD6.5) for Third-line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer (TRINITY).
Primary Endpoint	OrR was 12.40%, 14.30%, and 13.20% in all, DLL3-high, and DLL3-positive patients,respectively. Median OS was 5.60 months in all patients and 5.70 months in DLL3-high patients.
Experiment 20 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Objective Response Rate (ORR)	17.14 8.82 %
Patients Enrolled	101 with NEC/NET (large-cell NEC, gastroenteropancreatic NEC, neuroendocrine prostate cancer, and other NEC/NET) and 99 with other solid tumors (melanoma, medullary thyroid cancer [MTC], glioblastoma, and other).
Administration Dosage	The recommended phase II dose (RP2D) was 0.30 mg/kg every 6 weeks (q6w) for two cycles.
Related Clinical Trial
NCT Number	NCT02709889	Clinical Status	Phase 1/2
Clinical Description	An open-label study of rovalpituzumab tesirine in subjects with delta-like protein 3-expressing advanced solid tumors.
Primary Endpoint	The recommended phase II dose (RP2D) was 0.30 mg/kg every 6 weeks (q6w) for two cycles. At the RP2D, grade 3/4 adverse events included anemia (17.00%), thrombocytopenia (15.00%), and elevated aspartate aminotransferase (8.00%). Responses were confirmed in 15/145 patients (10.34%) treated at 0.30 mg/kg, including 9/69 patients (13.04%) with NEC/NET. Rova-T at 0.30 mg/kg q6w had manageable toxicity, with antitumor activity observed in patients with NEC/NET, melanoma, MTC, and glioblastoma.    Click to Show/Hide
Other Endpoint	In pooled patients with NEC/NET expressing a high level of DLL3 (50% DLL3-positive tumor cells), the ORR was 17.14% (6/35) and 34.29% (12/35) had a BOR (all PRs). In those with NEC/NET expressing a low level of DLL3 (1-49% DLL3-positive tumor cells), the ORR was 8.82% (3/34) and the BOR rate was 14.70% (5/34) (all PRs). The median PFS values for pooled patients with NEC/NET expressing high and low levels of DLL3 were 4.30 months (95% CI, 2.7-6.1) and 3.30 months (95% CI, 2.40-4.80), respectively. The median OS values for patients expressing high and low levels of DLL3 were 7.40 months (95% CI, 5.60-13.10) and 7.10 months (95% CI, 4.30-9.90), respectively.    Click to Show/Hide
Experiment 21 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Objective Response Rate (ORR)	34.50 31.60 50.00 50.00 %
Patients Enrolled	Progressive small-cell lung cancer (SCLC) who had previously been treated with at least one prior line of platinum-containing chemotherapy were enrolled if they were naive to PD-1/PD-L1targeting agents, had ECOG performance status 0-1, measurable disease per RECIST v1.1 or disease evaluable by tumor antigen assessment, and adequate bone marrow, cardiac, hepatic, and renal functions.    Click to Show/Hide
Administration Dosage	Budigalimab 375 mg via intravenous infusion every 3 weeks and Rova-T was administered as a dose of 0.30 mg/kg intravenously, on day 1 of the first and third 3-week cycle.
Related Clinical Trial
NCT Number	NCT03000257	Clinical Status	Phase 1
Clinical Description	A multicenter, phase 1, open-label, dose-escalation study of ABBV-181 as monotherapy and in combination with another anti-cancer therapy in subjects with advanced solid tumors.
Primary Endpoint	In patients with DLL3 score 75.00% (n = 19) the response rate was similar to the total evaluable population, with an ORR of 21.10% (90% CI: 7.50-41.90).
Experiment 22 Reporting the Activity Date of This ADC					[23]
Efficacy Data	Objective Response Rate (ORR)	50.00 63.00 33.00 %
Patients Enrolled	Extensive-stage small-cell lung cancer (ES SCLC), with a response of stable disease or better after the prestudy CE cycle per the Response Evaluation Criteria in Solid Tumors version 1.1, Eastern Cooperative Oncology Group performance status of 0 to 1, and absent or treated central nervous system metastases.
Administration Dosage	Rova-T monotherapy (0.30 mg/kg, every 6 [q6] wk 2; cohort 1; n = 4); Rova-T induction (0.30 mg/kg, q6 wk 2) followed by CE every 21 days (q21) 4 (cohort 2; n = 5); Rova-T (0.10 or 0.20 mg/kg, q6 wk 2) overlapping with CE q21 4 (cohort 3; n = 14); and Rova-T maintenance (0.30 mg/kg, q6 wk 2) after CE q21 4 (cohort 4; n = 3).
Related Clinical Trial
NCT Number	NCT02819999	Clinical Status	Phase 1
Clinical Description	A study of rovalpituzumab tesirine (SC16LD6.5) in the frontline treatment of patients with extensive stage small cell lung cancer.
Primary Endpoint	Median age was 66 years, and 73.00% had Eastern Cooperative Oncology Group performance status of 1. In cohort 3,seven patients (50%) had confirmed objective responses,with a median progression-free survival of 5.20 months and median overall survival of 10.30 months.

Experiment 1 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 16%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-415x)
Experiment 2 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 30%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-415x)
Experiment 3 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 33%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg weekly x 1.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-415x)
Experiment 4 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 40.74%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-452x)
Experiment 5 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 50.90%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.1 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-519x)
Experiment 6 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 59.81%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-452x)
Experiment 7 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 73.87%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-519x)
Experiment 8 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 78.50%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-452x)
Experiment 9 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 83%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-415x)
Experiment 10 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.14%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
In Vivo Model	Neuroblastoma PDX model (PDX: COG-N-519x)
Experiment 11 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.83%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.6 mg/kg.
In Vivo Model	Neuroblastoma PDX model

Experiment 1 Reporting the Activity Date of This ADC					[24]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99%	High DLL3 expression (DLL3+++)
Method Description	The inhibitory activity of Rova-T against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg weekly x 3.
In Vivo Model	COG-N-415 neuroblastoma model
In Vitro Model	Neuroblastoma	COG-N-415 cells		CVCL_AQ23

Experiment 1 Reporting the Activity Date of This ADC					[25]
Efficacy Data	Progression Free Survival	9.1 months
Patients Enrolled	Key inclusion criteria: Adults (≥18 years, ≥16 in US) with relapsed/refractory cHL (≥3 prior therapies including BV+CPI, or ≥2 if HSCT-ineligible), measurable disease (Lugano 2014), ECOG 0-2, and adequate organ function. FFPE tumor tissue and negative beta-HCG (WOCBP) required. Contraception mandated for 9.5 months (females) or 6.5 months (males) post-treatment.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT04052997	Clinical Status	PHASE2
Clinical Description	A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Primary Endpoint	The study evaluates efficacy endpoints including ORR (CR+PR per Lugano 2014), DOR (time from first response to progression/death), CR rate, RFS (time from CR to progression/death), PFS (time from first dose to progression/death), and OS (time from first dose to death). Safety assessments cover TEAEs (from first dose to 30 days post-last dose or new therapy start), SAEs (life-threatening events/hospitalization), ECOG status (0-5 scale), and HSCT recipients. PK parameters (Cmax, AUC, CL, T1/2, Vss, AI) are analyzed for total antibody, PBD-conjugated antibody, and SG3199 warhead across Cycles 1-2 (21-day cycles). ADA responses and HRQoL changes (EQ-5D-5L VAS, FACT-Lym) are monitored.    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[26]
Efficacy Data	Overall response (OR)	71%
Patients Enrolled	Eligible participants were adults (&ge;18 years) with relapsed/refractory lymphoma (WHO-confirmed), ECOG 0-2, adequate organ function (ANC&ge;1500/uL, platelets&ge;75,000/uL, bilirubin&le;1.5&times;ULN), and measurable disease (Lugano 2014). Exclusions included active GVHD, recent transplant (<60 days), autoimmune diseases, uncontrolled comorbidities (e.g., QTc&ge;450ms), or prior ADCT-301 hypersensitivity. Pregnancy, breastfeeding, or inadequate recovery from prior therapy (non-hematologic toxicity >Grade 1) also excluded participation.    Click to Show/Hide
Administration Dosage	Participants received an intravenous (IV) infusion of camidanlumab tesirine (3 ug/kg) on Day 1 of each 3-week treatment cycle, for a maximum of 2 cycles.
Related Clinical Trial
NCT Number	NCT02432235	Clinical Status	PHASE1
Clinical Description	A Phase 1 Adaptive Dose-Escalation Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Antitumor Activity of ADCT-301 in Patients With Relapsed or Refractory Hodgkin Lymphoma and Non-Hodgkin Lymphoma
Primary Endpoint	The study evaluated dose-limiting toxicities (DLTs) during Cycle 1-2 (21-day cycles), including hematologic (Grade 3-4 febrile neutropenia, Grade 4 thrombocytopenia/anemia) and non-hematologic events (Grade 4 tumor lysis, ≥Grade 3 AEs, ≥Grade 2 neuropathy/skin ulcers). The recommended Phase 2 dose was determined by safety data. Treatment-emergent AEs (TEAEs) and serious AEs (SAEs) were monitored for 84 days post-last dose (median treatment: 43 days).    Click to Show/Hide
Other Endpoint	Efficacy endpoints per Lugano 2014 criteria included ORR (CR: complete metabolic/radiologic response; PR: >50% node reduction), DoR (time from response to progression/death), PFS (time from first dose to progression/death), and OS (time to death). Pharmacokinetics (Cmax, Tmax, AUC, half-life, clearance) were analyzed for HuMax-TAC antibody, PBD-conjugated antibody, and free warhead SG3199 across Cycles 1-2. ADA responses were assessed via ECLIA.    Click to Show/Hide
Experiment 3 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Objective Response Rate (ORR)	28%
Patients Enrolled	Eligible participants were adults with advanced/metastatic solid tumors (specific types varied by study phase) refractory to standard therapy, measurable disease per RECIST, ECOG 0-1, and adequate organ function. Key exclusions included autoimmune diseases, recent infections linked to GBS, active CNS metastases, significant comorbidities, or prior CD25 antibody therapy. Combination therapy cohorts excluded patients with intolerance/history of severe immune-related toxicities from checkpoint inhibitors. Contraception requirements were strictly enforced.    Click to Show/Hide
Administration Dosage	Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of each cycle. Participants treated with camidanlumab tesirine as monotherapy, in the initial dose cohort will receive 20 ug/kg Q3W and the highest dose was 150 ug/kg Q3W.
Related Clinical Trial
NCT Number	NCT03621982	Clinical Status	PHASE1
Clinical Description	A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
Primary Endpoint	The safety profile was assessed through treatment-emergent adverse events (TEAEs) graded by CTCAE v4.0, including serious adverse events (SAEs), dose interruptions/reductions, and dose-limiting toxicities (DLTs) observed during ADCT-301 monotherapy and combination therapy with pembrolizumab over up to 3 years. Safety monitoring covered clinical lab values, vital signs, ECG, and ECOG performance status.    Click to Show/Hide
Other Endpoint	Efficacy endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) per RECIST v1.1. Pharmacokinetic parameters (Tmax, AUC, Cmax, clearance, half-life) and anti-drug antibody (ADA) responses were evaluated for ADCT-301 components in serum during treatment cycles, with discontinuation of PK/ADA sampling if therapy switched to pembrolizumab alone.    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[27]
Efficacy Data	Disease control rate (DCR)	44%
Patients Enrolled	Eligible participants were adults with advanced/metastatic solid tumors (specific types varied by study phase) refractory to standard therapy, measurable disease per RECIST, ECOG 0-1, and adequate organ function. Key exclusions included autoimmune diseases, recent infections linked to GBS, active CNS metastases, significant comorbidities, or prior CD25 antibody therapy. Combination therapy cohorts excluded patients with intolerance/history of severe immune-related toxicities from checkpoint inhibitors. Contraception requirements were strictly enforced.    Click to Show/Hide
Administration Dosage	Camidanlumab tesirine is administered as a 30-minute intravenous (IV) infusion on Day 1 of each cycle. Participants treated with camidanlumab tesirine as monotherapy, in the initial dose cohort will receive 20 ug/kg Q3W and the highest dose was 150 ug/kg Q3W.
Related Clinical Trial
NCT Number	NCT03621982	Clinical Status	PHASE1
Clinical Description	A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors
Primary Endpoint	The safety profile was assessed through treatment-emergent adverse events (TEAEs) graded by CTCAE v4.0, including serious adverse events (SAEs), dose interruptions/reductions, and dose-limiting toxicities (DLTs) observed during ADCT-301 monotherapy and combination therapy with pembrolizumab over up to 3 years. Safety monitoring covered clinical lab values, vital signs, ECG, and ECOG performance status.    Click to Show/Hide
Other Endpoint	Efficacy endpoints included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) per RECIST v1.1. Pharmacokinetic parameters (Tmax, AUC, Cmax, clearance, half-life) and anti-drug antibody (ADA) responses were evaluated for ADCT-301 components in serum during treatment cycles, with discontinuation of PK/ADA sampling if therapy switched to pembrolizumab alone.    Click to Show/Hide
Experiment 5 Reporting the Activity Date of This ADC					[28]
Patients Enrolled	Inclusion: Adults &ge;18 with relapsed/refractory AML, MDS, or MDS/MPN post-allogeneic transplant, stable GVHD (grade 1), creatinine clearance &ge;60ml/min, liver function within limits, no pregnancy, and immune suppression &le;20mg prednisone/day. Exclusion: Active infections, CNS disease, recent cancer therapy (3 years), hypersensitivity to CD25 antibodies, severe autoimmune diseases, or recent infections (HSV, EBV, CMV, SARS-CoV-2, etc.).    Click to Show/Hide
Administration Dosage	Patients will receive ADCT-301 37.5 ug/kg infused day 1,8, and 15 of a q3week cycle. Patients will have up to 2 cycles to assess response and safety to therapy and if they are not progressing may continue for up to 6 cycles.
Related Clinical Trial
NCT Number	NCT04639024	Clinical Status	PHASE2
Clinical Description	An Open-label Pilot Study to Evaluate the Safety and Efficacy of ADCT-301 in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Myeloproliferative Neoplasms.
Primary Endpoint	The study evaluates ADCT-301's morphologic complete response rate (primary endpoint, up to 3 years) and safety (adverse events within 12 weeks post-last dose).
Experiment 6 Reporting the Activity Date of This ADC					[29]
Patients Enrolled	Eligibility requires relapsed/refractory CD25+ AML/ALL (WHO criteria), ECOG 0-2, adequate organ function (creatinine &le;1.5mg/dL, ALT/AST &le;2&times;ULN, bilirubin &le;1.5&times;ULN), and WBC <15,000/uL. Exclusions include active CNS leukemia, GVHD, recent transplant (&le;60 days), HIV/HBV/HCV, QTc &ge;450ms, prior immunogenicity to CD25 antibodies, or other malignancies (exceptions: non-melanoma skin cancer, in situ cancers). Concurrent experimental therapies or unresolved toxicities (>Grade 1) are prohibited.    Click to Show/Hide
Administration Dosage	Weekly administration - Participants will receive an IV infusion of ADCT-301, on Days 1, 8, and 15 of each 3-week (21-day) cycle.3-week administration - Participants will receive an IV infusion of ADCT-301, on Day 1 of each 3-week (21-day) cycle.The dose escalation will be conducted according to a 3+3 design.
Related Clinical Trial
NCT Number	NCT02588092	Clinical Status	PHASE1
Clinical Description	A Phase 1, Open-label, Dose-escalation, Multicenter Study to Evaluate the Tolerability, Safety, Pharmacokinetics, and Activity of ADCT 301 in Patients With Relapsed or Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia
Primary Endpoint	The study evaluates dose-limiting toxicities (DLTs) in Cycle 1 (Days 1-21), defining hematologic DLTs as Grade 3+ neutropenia/thrombocytopenia or Grade 4 anemia with hypocellular marrow (≥6 weeks) and non-hematologic DLTs as Grade 4 tumor lysis, Grade 3+ AEs (excluding alopecia), or Grade 2+ neuropathy. The recommended dose for Part 2 is determined by safety data from Part 1. Treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs) are monitored up to 24 weeks post-treatment, with SAEs including life-threatening events, hospitalization, or death.    Click to Show/Hide
Other Endpoint	Efficacy endpoints include duration of response (DOR) from first response to progression/death, overall response rate (ORR) as CR/CRi/PR rates, and overall survival (OS) from first dose to death. Pharmacokinetics (Cmax, Tmax, AUC, half-life, clearance) are analyzed for PBD-conjugated antibody, total antibody, and free warhead (SG3199) in Q3W and QW dosing schedules. Anti-drug antibodies (ADA) are assessed through Cycle 2.    Click to Show/Hide
Experiment 7 Reporting the Activity Date of This ADC					[30]
Efficacy Data	Complete Remission (CR)	48.60 35.00 6.50 10.00 7.10 0.00 %
Patients Enrolled	Relapsed or refractory classical Hodgkin lymphoma or non-Hodgkin lymphoma, an Eastern Cooperative Oncology Group performance status 0-2, who had no therapies available to them with established clinical benefit for their disease stage were enrolled.
Administration Dosage	Intravenously (3-150 ug/kg) once every 3 weeks.
Related Clinical Trial
NCT Number	NCT02432235	Clinical Status	Phase 1
Clinical Description	A phase 1 adaptive dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-301 in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
Primary Endpoint	The maximum tolerated dose was not reached. The recommended doses for expansion were 30 ug/kg and 45 ug/kg for patients with classical Hodgkin lymphoma and 80 ug/kg for patients with T-cell non-Hodgkin lymphomas. No recommended doses for expansion were defined for B-cell non-Hodgkin lymphomas.
Other Endpoint	In the cHL cohort,ORR (95% CI) was 86.49% at 45 ug/kg (32/37 patients [71.20-95.50]) and 55.00% at 30 ug/kg (11/20 patients [31.50-76.90]); 48.65% (18/37 patients) and 35.00% (7/20 patients) achieved CR. Median (95% CI) DOR for the cHL population was 6.64 months (5.06-8.11),and was 7.16 months (4.57-8.51) in patients treated at 45 ug/kg.
Experiment 8 Reporting the Activity Date of This ADC					[31]
Patients Enrolled	Antecedent myelodysplastic syndrome who received treatment with hypomethylating agents and subsequently presented with CD25-positive AmL, or patients with R/R CD25-positive acute lymphocytic leukemia (ALL) who had failed or were intolerant to any established therapy, or for whom no other treatment options were available.
Administration Dosage	Intravenously at 3-92 ug/kg once every three weeks (Q3W) or 30 or 37.50 ug/kg every week (QW).
Related Clinical Trial
NCT Number	NCT02588092	Clinical Status	Phase 1
Clinical Description	A phase 1, open-label, dose-escalation, multicenter study to evaluate the tolerability, safety, pharmacokinetics, and activity of ADCT 301 in patients with relapsed or refractory CD25-positive acute myeloid leukemia (AML) or CD25-positive acute lymphoblastic leukemia.
Primary Endpoint	Two patients achieved complete responses with incomplete hematologic recovery; one each at 30.00 and 37.50 ug/kg QW.
Other Endpoint	Of 16 patients with post-baseline disease assessments, two patients treated on the QW dosing regimen had a complete response (CR).
Experiment 9 Reporting the Activity Date of This ADC					[32]
Patients Enrolled	Relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma.
Administration Dosage	45 ug/kg Q3W for 2 cycles and then 30 ug/kg Q3W thereafter; intravenous administration.
Related Clinical Trial
NCT Number	NCT02432235	Clinical Status	Phase 1
Clinical Description	A phase 1 adaptive dose-escalation study to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of ADCT-301 in patients with relapsed or refractory Hodgkin lymphoma and non-Hodgkin lymphoma.
Primary Endpoint	The ORR was 40%,representing 51 responders (patients achieved a best overall response of confirmed PR).
Other Endpoint	Of the 130 patients included in the safety analysis, 27 (20.77%) experienced grade2 increased GGT, 17 (13.08%) experienced a grade2 neurologic AE,and 18 (13.85%) experienced a grade2 autoimmune AE at cycle 6.

Experiment 1 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 11.60%	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm3 as a single dose at 0.1 mg/kg.    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 2 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 41.50%	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm3 at single doses of 0.3 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS).    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 3 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 51.30%	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm3 at single doses of 0.3 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS).    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 4 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.40%	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm3 as a single dose at 0.2 mg/kg.    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 5 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 93.20%	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm3 as a single dose at 0.4 mg/kg.    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 6 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.10%	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm3 at single doses of 0.6 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS).    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 7 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.10%	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000).Vechicle (PBS), ADCT-301 (dar 2.2), nonbinding ADC (DAR 2.1) or Adcetris (DAR~4) were administered intravenously at a mean Karpas 299 tumor volume of 130mm3 as single doses at 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 8 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.40%	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Karpas 299 with moderate CD25 expression (molecules per cell surface=76000). Compared with injection of vehicle (PBS), ADCT-301 administered intravenously (i.v.) at a mean tumor volume of 160 mm3 as a single dose at 0.6mg/kg.    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 9 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.80%	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	Camidanlumab tesirine induces efficient tumor cell killing in CDX models of an anaplastic large cell lymphoma (ALCL) cell line Su-DHL-1 with high CD25 expression (molecules per cell surface=310000).ADCT-301 was administered intravenously at mean tumor volume of 155 mm3 at single doses of 0.6 mg/kg and tumor growth compared with that observed after injection of vehicle (PBS).    Click to Show/Hide
In Vivo Model	Anaplastic large cell lymphoma CDX model
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538

Experiment 1 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	0.26 pM	Moderate CD25 expression (CD25++; 17,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Chronic eosinophilic leukemia	EoL-1 cells		CVCL_0258
Experiment 2 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	4.96 pM	High CD25 expression (CD25+++; 310,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Anaplastic large cell lymphoma	SU-DHL-1 cells		CVCL_0538
Experiment 3 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	17.07 pM	Moderate CD25 expression (CD25++; 76,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	ALK-positive anaplastic large cell lymphoma	Karpas-299 cells		CVCL_1324
Experiment 4 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	19.6 pM	High CD25 expression (CD25+++; 167,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Hodgkin lymphoma	HDLM-2 cells		CVCL_0009
Experiment 5 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Adult acute myeloid leukemia	KG-1 cells		CVCL_0374
Experiment 6 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	T lymphocytic leukemia	HuT 78 cells		CVCL_0337
Experiment 7 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Burkitt lymphoma	Daudi cells		CVCL_0008
Experiment 8 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	> 6667 pM	Negative CD25 expression (CD25-; <1,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Burkitt lymphoma	Ramos cells		CVCL_0597
Experiment 9 Reporting the Activity Date of This ADC					[33]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	7.49 1.11 pM ng/mL	Moderate CD25 expression (CD25++; 96,000 CD25 molecules/cell)
Method Description	The inhibitory activity of ADCT-301 against cancer cell growth was evaluated in various human cancer cell lines in vitro. CD25-positive and -negative cell lines were incubated with increasing concentrations of ADCT-301 or free warhead (SG3199) for 96 hours before processing by the MTS assay.
In Vitro Model	Hodgkin lymphoma	L-540 cells		CVCL_1362

Experiment 1 Reporting the Activity Date of This ADC					[34]
Patients Enrolled	Key eligibility: CD22+ (&ge;20% blasts) B-ALL patients (Ph+ allowed after TKI failure) with &ge;5% marrow blasts, ECOG 0-2, adequate organ function (Cr&le;1.5mg/dL, LVEF&ge;45%), WBC<15K/uL. Exclusions: active CNS leukemia, GVHD, recent transplant (<60d), HIV/HepB/C+, ADA+, prior VOD, uncontrolled comorbidities, or recent anticancer therapy (<14d/5 half-lives). Strict contraception required (16 weeks post-treatment).    Click to Show/Hide
Administration Dosage	Patients receive ADCT-602 by vein over 30 minutes on day 1. Courses repeat every 21 in the absence of disease progression or unacceptable toxicity. Patients who achieve CR/CRi receive ADCT-602 every 28 days.
Related Clinical Trial
NCT Number	NCT03698552	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Phase I/II Study to Evaluate the Safety and Anti-Tumor Activity of ADCT-602 Targeting CD22 in Patients with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Primary Endpoint	Primary objectives include MTD determination via 3+3 dose escalation (DLTs assessed over 21 days), toxicity incidence (CTCAE-graded), RP2D selection, and CR/CRi rate evaluation (Simon's two-stage design) in relapsed/refractory B-ALL patients.
Other Endpoint	Secondary endpoints comprise ORR, OS, PFS, PK profiling (4 samples within 6h post-dose), and QT interval assessment via EKG monitoring.
Experiment 2 Reporting the Activity Date of This ADC					[35]
Related Clinical Trial
NCT Number	NCT03698552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study to evaluate the safety and anti-tumor activity of ADCT-602 targeting CD22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Experiment 3 Reporting the Activity Date of This ADC					[36]
Patients Enrolled	R/R B-acute lymphocytic leukemia (ALL).
Administration Dosage	A 3+3 dose-escalation design was used for phase 1. ADCT-602 was initially given IV once every 3 weeks (30 ug/kg, n=3; 60 ug/kg, n=4; 90 ug/kg, n=4); based on the PK data, the administration schedule was later amended to weekly infusions (30 ug/kg, n=3; 40 ug/kg, n=4; 50 ug/kg, n=3).
Related Clinical Trial
NCT Number	NCT03698552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study to evaluate the safety and anti-tumor activity of ADCT-602 targeting CD22 in patients with relapsed or refractory b-cell acute lymphoblastic leukemia.
Primary Endpoint	In this phase 1 study in pts with very heavily pretreated R/R B-ALL with a median of 5 prior lines of therapy and high baseline bone marrow tumor burden, single-agent ADCT-602 was well tolerated with no DLTs noted. Two pts achieved MRD-negative remission. Dose escalation in the weekly schedule continues and 2 additional dose levels (40 ug/kg weekly and 50 ug/kg weekly) are planned. PK data, available for 9 pts treated at every 3-week schedule [30 ug/kg, n=3; 60 ug/kg, n=4; 90 ug/kg, n=2] showed rapid clearance of antibody with mean apparent half-life of <1 day during Cycle 1. This supported transitioning ADCT-602 administration to the weekly dosing.    Click to Show/Hide
Experiment 4 Reporting the Activity Date of This ADC					[37]
Patients Enrolled	R/R B-acute lymphocytic leukemia (ALL).
Administration Dosage	A 3+3 dose-escalation design was used for phase 1. ADCT-602 was initially given IV once every 3 weeks (30 ug/kg, n=3; 60 ug/kg, n=4; 90 ug/kg, n=4); based on the PK data, the administration schedule was later amended to weekly infusions (30 ug/kg, n=3; 40 ug/kg, n=4; 50 ug/kg, n=3).
Related Clinical Trial
NCT Number	NCT03698552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study to evaluate the safety and anti-tumor activity of ADCT-602 targeting CD22 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia.
Primary Endpoint	In this phase 1 study in pts with very heavily pretreated R/R B-ALL with a median of 5 prior lines of therapy and high baseline bone marrow tumor burden, single-agent ADCT-602 was well tolerated with one pt with DLT noted at the 50 mg/kg weekly dose level. Notably, all 3 pts treated at this dose level had evidence of clinical activity with 2/3 pts achieving MRD negative CR.    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[38]
Patients Enrolled	Eligible participants had advanced/metastatic solid tumors (cholangiocarcinoma, ovarian/prostate/RCC/TNBC), measurable disease per RECIST v1.1 (prostate cancer allowed with bone metastases + PSA ≥2 ng/mL). Exclusions included active infections, symptomatic CNS metastases (unless treated/asymptomatic for ≥4 weeks), clinically significant effusions, CTCAE Grade 2+ diarrhea, ocular surface disease (except managed mild dry eye), and recent experimental drug use (14-day washout).    Click to Show/Hide
Administration Dosage	Part 1: pts will receive escalating doses of ADCT-901 guided by a 3+3 design (1st dose: 15 ug/kg every 3 weeks [Q3W]; highest dose: 290 ug/kg Q3W). Dose escalation will be evaluated by administering the lowest dose to first 3 pts, then increasing/decreasing the dose based on dose-limiting toxicity (DLT) experienced by pts.
Related Clinical Trial
NCT Number	NCT04972981	Clinical Status	PHASE1
Clinical Description	A Phase 1, Open-Label, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 as Monotherapy in Patients With Selected Advanced Solid Tumors
Primary Endpoint	Safety was evaluated by AE/SAE incidence (including clinical lab/ECG changes) over 2.5 years, with DLTs tracked during dose escalation (Days 1-21), alongside dose modifications (interruptions/reductions).
Other Endpoint	Efficacy endpoints (ORR, DOR, PFS, OS) and comprehensive PK parameters (Cmax, Tmax, AUC metrics, half-life, clearance, ADA response) for ADCT-901 components (total antibody, PBD-conjugated antibody, SG3199) were monitored throughout the 2.5-year study period.

Experiment 1 Reporting the Activity Date of This ADC					[39]
Related Clinical Trial
NCT Number	NCT03859752	Clinical Status	Phase 1
Clinical Description	A phase 1, open label, first-in-human study of TR1801-ADC, an antibody drug conjugate (ADC), in patients with select solid tumors expressing c-met.

Experiment 1 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 1.02%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR3150)
Experiment 2 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 30.20%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0635)
Experiment 3 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 30.40%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0696)
Experiment 4 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 34.80%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR0126)
Experiment 5 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 35.40%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN3533)
Experiment 6 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 37.50%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR3150)
Experiment 7 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 44.60%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR0126)
Experiment 8 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.70%	Negative MET expression (MET-)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0696)
Experiment 9 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.70%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN3533)
Experiment 10 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 47.30%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0635)
Experiment 11 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 53.20%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0635)
Experiment 12 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 59.10%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN3533)
Experiment 13 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 60.40%	High MET expression (MET+++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0696)
Experiment 14 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 70.30%	High MET expression (MET+++; IHC H-score=300)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR3150)
Experiment 15 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 70.80%	High MET expression (MET+++; IHC H-score=295)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0635)
Experiment 16 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 70.90%	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR0126)
Experiment 17 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 76.50%	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN0696)
Experiment 18 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 79.40%	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA0152)
Experiment 19 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 80.50%	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Head and neck squamous cell carcinoma PDX model (PDX: HN3533)
Experiment 20 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 80.90%	High MET expression (MET+++; IHC H-score=300)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR0126)
Experiment 21 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 81.40%	High MET expression (MET+++; IHC H-score=300)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.125 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA3121)
Experiment 22 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 89.20%	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA0152)
Experiment 23 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 95.10%	High MET expression (MET+++; IHC H-score=300)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Colorectal cancer PDX model (PDX: CR3150)
Experiment 24 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.30%	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.25 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA3121)
Experiment 25 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 97.60%	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA0152)
Experiment 26 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.10%	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 0.5 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA3121)
Experiment 27 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA0152)
Experiment 28 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Moderate MET expression (MET++)
Method Description	Each mouse was subcutaneously inoculated at the right flank with a 23 mm (diameter) tumor piece of one of the tested PDX models. Mice were randomly grouped into six groups (n = 10 animals) according to the tumor size average of 200 mm3.A single dose of test articles was administered intravenously into the tail vein at the dose concentrations indicated. TR1801-ADC 1 mg/kg.    Click to Show/Hide
In Vivo Model	Gastric cancer PDX models (PDX: GA3121)

Experiment 1 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	68.30%	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Pharyngeal squamous cell carcinoma	Detroit 562 cells		CVCL_1171
Experiment 2 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	88.80%	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1573 cells		CVCL_1478
Experiment 3 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	90.50%	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-16 cells		CVCL_0076
Experiment 4 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	92.40%	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon adenocarcinoma	SW480 cells		CVCL_0546
Experiment 5 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	92.90%	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon adenocarcinoma	SW1417 cells		CVCL_1717
Experiment 6 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	95.20%	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung papillary adenocarcinoma	NCI-H441 cells		CVCL_1561
Experiment 7 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	95.50%	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 8 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	97.40%	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-1 cells		CVCL_0099
Experiment 9 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	97.50%	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-5 cells		CVCL_0078
Experiment 10 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	97.60%	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 11 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	97.80%	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	MKN45 cells		CVCL_0434
Experiment 12 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	98.10%	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Hypopharyngeal squamous cell carcinoma	FaDu cells		CVCL_1218
Experiment 13 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	98.90%	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon carcinoma	HCT 116 cells		CVCL_0291
Experiment 14 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	99.10%	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Cecum adenocarcinoma	NCI-H747 cells		CVCL_1587
Experiment 15 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Maximum inhibition efficiency (MIE)	99.30%	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-620 cells		CVCL_5079
Experiment 16 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.2 pM	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung papillary adenocarcinoma	NCI-H441 cells		CVCL_1561
Experiment 17 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	15.6 pM	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-5 cells		CVCL_0078
Experiment 18 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	15.8 pM	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	MKN45 cells		CVCL_0434
Experiment 19 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	190.2 pM	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon carcinoma	HCT 116 cells		CVCL_0291
Experiment 20 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	197.9 pM	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-620 cells		CVCL_5079
Experiment 21 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	327.5 pM	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Hypopharyngeal squamous cell carcinoma	FaDu cells		CVCL_1218
Experiment 22 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	346.4 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 23 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1380 pM	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon adenocarcinoma	SW480 cells		CVCL_0546
Experiment 24 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2272.7 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 25 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3230 pM	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Cecum adenocarcinoma	NCI-H747 cells		CVCL_1587
Experiment 26 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3494 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Colon adenocarcinoma	SW1417 cells		CVCL_1717
Experiment 27 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4664 pM	High MET expression (MET+++; IHC H-score=295)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-16 cells		CVCL_0076
Experiment 28 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.03 nM	High MET expression (MET+++; IHC H-score=300)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Pharyngeal squamous cell carcinoma	Detroit 562 cells		CVCL_1171
Experiment 29 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	13.44 nM	Moderate MET expression (MET++; IHC H-score=190)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1573 cells		CVCL_1478
Experiment 30 Reporting the Activity Date of This ADC					[40]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.37 nM	Moderate MET expression (MET++; IHC H-score=173)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Gastric adenocarcinoma	SNU-1 cells		CVCL_0099

Experiment 1 Reporting the Activity Date of This ADC					[41]
Efficacy Data	Progression Free Survival	3.9 months
Patients Enrolled	Eligible participants must be ≥18 years with metastatic castration-resistant prostate cancer (mCRPC) progressing after abiraterone/enzalutamide therapy. Key exclusions include prior PSMA-directed therapies, recent anti-cancer treatments (within 21 days), brain metastases requiring treatment, radiation affecting >25% marrow-bearing bone, or history of significant peripheral vasculopathies.    Click to Show/Hide
Administration Dosage	As of Sept 27 2019, 33 pts received MEDI3726. Median age was 71.0 yr. Median number of prior regimens was 4. Median follow-up was 5.4 mo. Drug-related AEs occurred in 30 (90.9%), being grade 3/4 in 15 (45.5%), serious in 11 (33.3%) and causing discontinuation in 13 (39.4%). There were no drug-related deaths. One pt at 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. No MTD was identified per mTPI; the MAD was 0.3 mg/kg.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT02991911	Clinical Status	PHASE1
Clinical Description	A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.
Primary Endpoint	The study evaluates safety through monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) from informed consent through 90 days post-treatment, with laboratory parameters, vital signs, and ECG changes assessed up to 21-90 days after last MEDI3726 dose.
Other Endpoint	Efficacy is measured via RECIST v1.1 response, PSA50 reduction, and circulating tumor cell (CTC) conversion over 12-90 days. Pharmacokinetic analysis includes MEDI3726 plasma concentration, Cmax, AUC, clearance, and half-life, alongside immunogenicity assessment through anti-drug antibodies (ADAs) during the 90-day follow-up period.
Experiment 2 Reporting the Activity Date of This ADC					[41]
Efficacy Data	Overall suvival (OS)	10.6 months
Patients Enrolled	Eligible participants must be ≥18 years with metastatic castration-resistant prostate cancer (mCRPC) progressing after abiraterone/enzalutamide therapy. Key exclusions include prior PSMA-directed therapies, recent anti-cancer treatments (within 21 days), brain metastases requiring treatment, radiation affecting >25% marrow-bearing bone, or history of significant peripheral vasculopathies.    Click to Show/Hide
Administration Dosage	As of Sept 27 2019, 33 pts received MEDI3726. Median age was 71.0 yr. Median number of prior regimens was 4. Median follow-up was 5.4 mo. Drug-related AEs occurred in 30 (90.9%), being grade 3/4 in 15 (45.5%), serious in 11 (33.3%) and causing discontinuation in 13 (39.4%). There were no drug-related deaths. One pt at 0.3 mg/kg had a DLT of Grade 3 thrombocytopenia. No MTD was identified per mTPI; the MAD was 0.3 mg/kg.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT02991911	Clinical Status	PHASE1
Clinical Description	A Phase 1/1b Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI3726 in Subjects With Metastatic Castration Resistant Prostate Cancer Who Have Received Prior Treatment With Abiraterone or Enzalutamide.
Primary Endpoint	The study evaluates safety through monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) from informed consent through 90 days post-treatment, with laboratory parameters, vital signs, and ECG changes assessed up to 21-90 days after last MEDI3726 dose.
Other Endpoint	Efficacy is measured via RECIST v1.1 response, PSA50 reduction, and circulating tumor cell (CTC) conversion over 12-90 days. Pharmacokinetic analysis includes MEDI3726 plasma concentration, Cmax, AUC, clearance, and half-life, alongside immunogenicity assessment through anti-drug antibodies (ADAs) during the 90-day follow-up period.
Experiment 3 Reporting the Activity Date of This ADC					[48]
Efficacy Data	Composite Response Rate (RR)	12.10%
Patients Enrolled	Patients with metastatic castration-resistant prostate cancer after disease progression on abiraterone and/or enzalutamide and taxane-based chemotherapy.
Administration Dosage	Administered at 0.015-0.30 mg/kg intravenously every 3 weeks until disease progression/unacceptable toxicity; The MTD was not identified; the MAD was 0.30 mg/kg.
Related Clinical Trial
NCT Number	NCT02991911	Clinical Status	Phase 1
Clinical Description	A phase 1/1b multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, immunogenicity, and antitumor activity of MEDI3726 in subjects with metastatic castration resistant prostate cancer who have received prior treatment with abiraterone or enzalutamide.

Experiment 1 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 15.86%	High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	PC-3 cells		CVCL_0035
Experiment 2 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 36.17%	Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.11 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 3 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 45.68%	High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	PC-3 cells		CVCL_0035
Experiment 4 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 68.20%	Moderate PSMA expression (PSMA++; 43,766 PSMA molecules/cell)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 5 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 76.95%	High PSMA expression (PSMA+++; 250,494 PSMA molecules/cell)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	LNCaP cells		CVCL_0395
Experiment 6 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 93.55%	Negative PSMA expression (PSMA-)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.33 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045
Experiment 7 Reporting the Activity Date of This ADC					[49]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 98.71%	Negative PSMA expression (PSMA-)
Method Description	The inhibitory activity of MEDI3726 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 1 mg/kg MEDI3726.
In Vivo Model	PC-3 CDX model
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045

Experiment 1 Reporting the Activity Date of This ADC					[42]
Patients Enrolled	Key eligibility: Adults (≥18) with HER2+ metastatic solid tumors, ECOG 0-2 (dose escalation)/0-1 (expansion), adequate organ function (ANC≥1500, platelets≥100K, bilirubin≤1.5×ULN, CrCl≥60). Exclusions: Grade≥3 antibody hypersensitivity, CNS metastases, active HBV/HCV/HIV, recent anticancer therapy, pregnancy, or uncontrolled comorbidities.    Click to Show/Hide
Administration Dosage	Part 1 (dose escalation): Participants received an infusion of ADCT-502, at escalating doses. Part 1 continued until the maximum tolerated dose or the recommended dose (s) and schedule (s) for expansion were determined.Part 2 (expansion): Participants were due to be assigned to the recommended dose level of ADCT-502 as identified in Part 1 by the Dose Escalation Steering Committee.    Click to Show/Hide
Related Clinical Trial
NCT Number	NCT03125200	Clinical Status	PHASE1
Clinical Description	A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression
Primary Endpoint	Primary endpoints include DLT assessment (Grade ≥3 per CTCAE v4) during first 21-day cycle, TEAE/SAE monitoring through treatment +30 days, and comprehensive safety evaluations (labs, physical exams, ECOG status, vitals, ECG).
Other Endpoint	Secondary objectives cover tumor response (ORR/DCR/DOR/PFS/OS assessed q12w per RECIST 1.1), PK analysis (AUC/Cmax/Tmax for total antibody, DAR≥0 species, PBD-conjugated antibody, free warhead SG3199), and immunogenicity (ADA titers).
Experiment 2 Reporting the Activity Date of This ADC					[46]
Efficacy Data	Objective Response Rate (ORR)	20%
Patients Enrolled	Patients with HER2-positive advanced solid tumors.
Administration Dosage	Seven dose cohorts (30, 60, 120, 150, 180, 210, 240 ug/kg on day 1, iv once every 3 weeks.
Related Clinical Trial
NCT Number	NCT03125200	Clinical Status	Phase 1
Clinical Description	A phase 1, open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of ADCT-502 in patients with advanced solid tumors with HER2 expression.

Experiment 1 Reporting the Activity Date of This ADC					[43]
Patients Enrolled	Eligible patients must be &ge;18 years with relapsed/refractory multiple myeloma (IMWG criteria) who exhausted standard therapies, have measurable disease, ECOG 0-1, and adequate organ function. Exclusions include recent stem cell transplants (<90 days), CNS involvement, plasma cell disorders, or conditions interfering with safety assessments.
Administration Dosage	Single agent MEDI2228, ADC (antibody drug conjugate) will be administered to adult subjects with relapsed/refractory (R/R) multiple myeloma (MM).
Related Clinical Trial
NCT Number	NCT03489525	Clinical Status	PHASE1
Clinical Description	A Phase 1, Open-label Study to Evaluate the Safety, Pharmacokinetics, Immunogenicity, and Preliminary Efficacy of MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
Primary Endpoint	The study evaluates safety through monitoring adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) from informed consent through 90 days post-treatment, including laboratory tests, vital signs, and ECG changes assessed up to 21 days after treatment completion.
Other Endpoint	Pharmacokinetic analysis measures MEDI2228 concentration, clearance, and half-life over 60 days post-treatment while assessing immunogenicity via anti-drug antibodies. Efficacy endpoints including objective response rate, clinical benefit rate, duration of response, progression-free survival, and overall survival are evaluated for up to three years post-enrollment.    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[47]
Efficacy Data	Objective Response Rate (ORR)	61%
Patients Enrolled	Eligible pts were 18 years old with confirmed relapsed/refractory multiple myeloma (R/R MM) as defined by International Myeloma Working Group consensus criteria, had measurable disease, and had an Eastern Cooperative Oncology Group performance status 1. Pts had to have progressed after treatment with three classes of standard-of-care anti-myeloma drugs, including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies (mAbs).    Click to Show/Hide
Administration Dosage	Administered in the dose of 0.0125-0.20 mg/kg intravenously every 3 weeks (Q3W); The maximum tolerated dose was 0.14 mg/kg Q3W.
Related Clinical Trial
NCT Number	NCT03489525	Clinical Status	Phase 1
Clinical Description	A phase 1, open-label study to evaluate the safety, pharmacokinetics, immunogenicity, and preliminary efficacy of MEDI2228 in subjects with relapsed/refractory multiple myeloma.

Experiment 1 Reporting the Activity Date of This ADC					[50]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.05%
Method Description	The inhibitory activity of MEDI-2228 against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg MEDI-2228.
In Vivo Model	NSG mice model
In Vitro Model	Plasma cell myeloma	MM1.S cells		CVCL_8792
Experiment 2 Reporting the Activity Date of This ADC					[50]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.46%
Method Description	The inhibitory activity of MEDI-2228+NK against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg MEDI-2228.
In Vivo Model	NSG mice model
In Vitro Model	Plasma cell myeloma	MM1.S cells		CVCL_8792
Experiment 3 Reporting the Activity Date of This ADC					[50]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99.94%
Method Description	The inhibitory activity of MEDI-2228+NK+Dara against cancer cell growth was evaluated in various human cancer cell lines in vivo. The cells were treated with 0.3 mg/kg MEDI-2228.
In Vivo Model	NSG mice model
In Vitro Model	Plasma cell myeloma	MM1.S cells		CVCL_8792

Experiment 1 Reporting the Activity Date of This ADC					[51]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 67.99%
Method Description	The inhibitory activity of MEDI-2228 against cancer cell growth was evaluated in various human cancer cell lines in vivo.The cells were treated with 0.4 mg/kg MEDI-2228.
In Vivo Model	CB17 SCID mice model
Experiment 2 Reporting the Activity Date of This ADC					[51]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 90.12%
Method Description	The inhibitory activity combination of M2 and btz for 2 weeks against cancer cell growth was evaluated in various human cancer cell lines in vivo.
In Vivo Model	CB17 SCID mice model

Experiment 1 Reporting the Activity Date of This ADC					[51]
Efficacy Data	Half Maximal Effective Dose (EC50)	189.7 ng/mL
Method Description	The inhibitory activity of MEDI-2228 against cancer cell growth was evaluated in various human cancer cell lines in vitro.
In Vitro Model	Plasma cell myeloma	RPMI-8226 cells		CVCL_0014

Experiment 1 Reporting the Activity Date of This ADC					[44]
Patients Enrolled	Eligible patients must have relapsed/refractory hematologic malignancies with no standard therapies available, be ≥18 years old, ECOG 0-1, and meet organ function criteria (liver, renal). Contraception is required for sexually active participants. Exclusions include recent chemotherapy/surgery/radiotherapy, unresolved toxicities, active infections (HIV/HBV/HCV), CNS involvement, or high bleeding risk. Prior autologous SCT within 120 days or unresolved transplant-related toxicities also disqualify.    Click to Show/Hide
Administration Dosage	The study will enroll patients with R/R AML/MM/DLBCL who will receive MEDI7247 IV
Related Clinical Trial
NCT Number	NCT03106428	Clinical Status	PHASE1
Clinical Description	A Phase 1 Multicenter, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, Immunogenicity and Antitumor Activity of MEDI7247 in Patients With Selected Relapsed/Refractory Hematological Malignancies
Primary Endpoint	The study evaluates safety endpoints including adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) monitored from informed consent through 90 days post-treatment. Laboratory parameters, vital signs, and ECG results are assessed for changes from baseline up to 21 days post-treatment, covering hematology, serum chemistry, coagulation, urinalysis, and cardiovascular metrics.    Click to Show/Hide
Other Endpoint	Pharmacokinetic (PK) analysis of MEDI7247 includes maximum concentration (Cmax), area under the curve (AUC), clearance, and terminal half-life, measured from informed consent through 30 days post-treatment. Immunogenicity is assessed via anti-drug antibodies (ADAs). Anti-tumor activity is evaluated by best overall response (BOR), objective response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), and overall survival (OS), tracked up to 3 years post-enrollment.    Click to Show/Hide
Experiment 2 Reporting the Activity Date of This ADC					[45]
Patients Enrolled	Eligible patients must have advanced/metastatic solid tumors refractory to standard therapies, be ≥18 years old, ECOG 0-1, and meet organ function criteria (liver, renal, hematologic). Contraception is required for sexually active participants. Exclusions include active CNS metastases (unless treated/stable), unresolved toxicities (>Grade 1), recent anticancer therapy (within 21 days), prior PBD-ADCs, high-risk cardiac conditions, active infections (HIV/HBV/HCV), pregnancy, or concurrent investigational studies. Major surgery or significant trauma within 21 days also disqualifies.    Click to Show/Hide
Administration Dosage	Subjects with advanced solid tumors will enroll into the respective arms to receive Medi7247 IV at prescribed dose and schedule
Related Clinical Trial
NCT Number	NCT03811652	Clinical Status	PHASE1
Clinical Description	A Phase 1/1b Multicenter, Open-label, Dose-escalation, and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI7247 in Patients With Advanced or Metastatic Disease in Selected Solid Tumors
Primary Endpoint	The study evaluates safety outcomes including adverse events (AEs), serious adverse events (SAEs), and dose-limiting toxicities (DLTs) monitored from informed consent through 90 days post-treatment. Laboratory parameters, vital signs, and ECG results are assessed for changes from baseline up to 90 days post-treatment, covering hematology, serum chemistry, urinalysis, and coagulation metrics.    Click to Show/Hide
Other Endpoint	Pharmacokinetic (PK) analysis of MEDI7247 includes maximum concentration (Cmax), terminal half-life (t1/2), area under the curve (AUC), and clearance, measured from first dose through 90 days post-treatment. Immunogenicity is assessed via anti-drug antibodies (ADAs). Anti-tumor activity is evaluated by best overall response (BOR), objective response rate (ORR), time to response (TTR), duration of response (DoR), progression-free survival (PFS), disease control (DC), and overall survival (OS), tracked up to 2 years post-enrollment.    Click to Show/Hide

Experiment 1 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 40.50%	Negative expression (HER2-)
Method Description	The antitumor activity of trastuzumab-C239i-SG3400 was evaluated in the low-HER2-expressing,trastuzumab-resistant human breast cancer model JIMT-1 and the HER2-positive human gastric cancer xenograft model NCI-N87. A sub-curative single dose of ADC of 1 mg/kg was chosen for both ADCs to observe any difference in activity.
In Vivo Model	Breast cancer CDX model
In Vitro Model	Breast cancer	Breast cancer cells		Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 48%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of trastuzumab-C239i-SG3400 was evaluated in the low-HER2-expressing,trastuzumab-resistant human breast cancer model JIMT-1 and the HER2-positive human gastric cancer xenograft model NCI-N87. A sub-curative single dose of ADC of 1 mg/kg was chosen for both ADCs to observe any difference in activity.
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric cancer	Gastric cancer cells		Homo sapiens

Experiment 1 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	10.7 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	20.9 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	23.3 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 4 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 50 ng/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 5 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 250 ng/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077

Experiment 1 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 62.20%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of trastuzumab-C239i-SG3600 was evaluated in the low-HER2-expressing,trastuzumab-resistant human breast cancer model JIMT-1 and the HER2-positive human gastric cancer xenograft model NCI-N87. A sub-curative single dose of ADC of 1 mg/kg was chosen for both ADCs to observe any difference in activity.
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric cancer	Gastric cancer cells		Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 65.10%	Negative expression (HER2-)
Method Description	The antitumor activity of trastuzumab-C239i-SG3600 was evaluated in the low-HER2-expressing,trastuzumab-resistant human breast cancer model JIMT-1 and the HER2-positive human gastric cancer xenograft model NCI-N87. A sub-curative single dose of ADC of 1 mg/kg was chosen for both ADCs to observe any difference in activity.
In Vivo Model	Breast cancer CDX model
In Vitro Model	Breast cancer	Breast cancer cells		Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Low HER2 expression (HER2+)
Method Description	The antitumor activity of trastuzumab-C239i-SG3600 was evaluated in the low-HER2-expressing,trastuzumab-resistant human breast cancer model JIMT-1 and the HER2-positive human gastric cancer xenograft model NCI-N87. A sub-curative single dose of ADC of 3 mg/kg was chosen for both ADCs to observe any difference in activity.
In Vivo Model	Gastric cancer CDX model
In Vitro Model	Gastric cancer	Gastric cancer cells		Homo sapiens

Experiment 1 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	16.1 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.1 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	33.9 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 4 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10 ug/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 5 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10 ug/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031

Experiment 1 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 82.20%	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-Flexmab-SG3710 was investigated after single-dose injections (0.30 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts. NCI-N87 cells (5 x106) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm3.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.20%	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-Flexmab-SG3710 was investigated after single-dose injections (0.6 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts. NCI-N87 cells (5 x106) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm3.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 3 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 92.80%	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-Flexmab-SG3710 and trastuzumab-C239i-SG3249 ADCs was investigated after single-dose injections (1 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts,and tumor growth was monitored for 85 days. NCI-N87 cells (5 x106) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm3.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	35.5 pM	Low HER2 expression (HER2+)
Method Description	The cytotoxic effect of Trastuzumab-Flexmab-SG3710 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing breast and gastric cancers. The potency of trastuzumab-Flexmab-SG3710 was assessed on the SKBR-3 cell line after five days of incubation.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[54]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 91.30%	Positive 5T4 expression (5T4+++/++)
Method Description	A single dose of 5T4-PBD was administrated at 0.1 and 0.3 mg/kg intravenously into nude mice.
In Vivo Model	MDA-MB-361 CDX model
In Vitro Model	Breast adenocarcinoma	MDA-MB-361 cells		CVCL_0620

Experiment 1 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94%	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-C239i-SG3249 was investigated after single-dose injections (0.30 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts. NCI-N87 cells (5 x106) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm3.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 2 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 94.20%	Low HER2 expression (HER2+)
Method Description	The in vivo efficacy of trastuzumab-Flexmab-SG3710 and trastuzumab-C239i-SG3249 ADCs was investigated after single-dose injections (1 mg/kg) in female athymic mice bearing NCI-N87 HER2-positive subcutaneous xenografts,and tumor growth was monitored for 85 days. NCI-N87 cells (5 x106) in 50% Matrigel were inoculated subcutaneously into 46 week-old female athymic nude mice. Five mice per group were dosed intravenously five days after their tumors reached a volume of 200 mm3.    Click to Show/Hide
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603

Experiment 1 Reporting the Activity Date of This ADC					[53]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	14.4 pM	Low HER2 expression (HER2+)
Method Description	The cytotoxic effect of Trastuzumab-C239i-SG32490 was assessed in cell viability assays for a diverse panel of human solid tumor cell lines representing breast and gastric cancers. The potency of trastuzumab-Flexmab-SG3710 was assessed on the SKBR-3 cell line after five days of incubation.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[55]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 96.50%	Positive La/SSB expression (La/SSB +++/++)
Method Description	ChDAB4-SG3249 (3 mg/kg, the day after chemotherapy (Day 3)) induces efficient tumor cell killing in cell line-derived models of Lewis lung carcinoma cell with HER3 expression with high expression.
In Vivo Model	LL2 CDX model
In Vitro Model	Normal	LL2 cells		CVCL_C4MM

Experiment 1 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	41.5 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 2 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	46 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 3 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	19.7 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 4 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511

Experiment 1 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	49 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 2 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	61.5 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 3 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	11.1 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 4 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	91 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511

Experiment 1 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	56 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 2 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	77.5 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 3 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	24.4 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 4 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	31.3 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465

Experiment 1 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	66 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 2 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	76.5 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 3 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	27.5 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 4 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.41 nM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511

Experiment 1 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	76.8 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 2 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Maximum inhibition efficiency (MIE)	78.7 pM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511
Experiment 3 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	21.8 pM	Moderate MET expression (MET++; IHC H-score=180)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1373 cells		CVCL_1465
Experiment 4 Reporting the Activity Date of This ADC					[56]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.15 nM	Moderate MET expression (MET++; IHC H-score=130)
Method Description	Cell viability was determined by measuring the luminescence after adding the CellTiter-Glo 2.0 reagent. Cancer cells were seeded overnight in growth media and incubated at 37°C, 5% CO2,and 95% humidity. starting with concentrations of 100 nM for ADCs for free drug. Cells were exposed to test articlesfor 5 days.
In Vitro Model	Lung adenocarcinoma	NCI-H1975 cells		CVCL_1511

Experiment 1 Reporting the Activity Date of This ADC					[57]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	1.74 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxic effect of Her-SG3249 was assessed in cell viability assays for breast cancer. The potency of Her-SG3249 was assessed on the SKBR-3 cell line. Process aggregation assessed by SEC.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[57]
Efficacy Data	Half Maximum Growth Inhibitory Concentration (GI50)	2.62 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxic effect of site-specific Her-SG3249 was assessed in cell viability assays for breast cancer. The potency of site-specific Her-SG3249 was assessed on the SKBR-3 cell line. Process aggregation assessed by SEC.
In Vitro Model	Breast adenocarcinoma	SK-BR-3 cells		CVCL_0033

Experiment 1 Reporting the Activity Date of This ADC					[58]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.31 nM	High EGFR expression (EGFR+++)
Method Description	1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
In Vitro Model	Breast adenocarcinoma	MDA-MB-468 cells		CVCL_0419
Experiment 2 Reporting the Activity Date of This ADC					[58]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.85 nM	High EGFR expression (EGFR+++)
Method Description	1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
In Vitro Model	Skin squamous cell carcinoma	A431 cells		CVCL_0037
Experiment 3 Reporting the Activity Date of This ADC					[58]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	9.07 nM	Moderate EGFR expression (EGFR++)
Method Description	1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
In Vitro Model	Invasive breast carcinoma of no special type	BT-20 cells		CVCL_0178
Experiment 4 Reporting the Activity Date of This ADC					[58]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 100 nM	Negative EGFR expression (EGFR-)
Method Description	1 x104 cells per well in a volume of 100 ul were plated in 96-well tissue culture plates. After 24 h, ADCs were added at the indicated concentrations. After 72 h, the medium was removed and the viability was determined using the CellTiter-Glo luminescent cell viability assay kit.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

Experiment 1 Reporting the Activity Date of This ADC					[59]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	235.6 nM	High HER2 expression (HER2+++)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Invasive breast carcinoma	BT474 HerDR cells		CVCL_0179
Experiment 2 Reporting the Activity Date of This ADC					[59]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	283.8 nM	High HER2 expression (HER2+++)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[59]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000 nM	Negative HER2 expression (HER2-)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031
Experiment 4 Reporting the Activity Date of This ADC					[59]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 1000 nM	Negative HER2 expression (HER2-)
Method Description	SKOV-3, BT474 HerDR, MDA-MB-231 and MCF-7 cells were cultured under various concentrations of Mil40, SN-38 and ADCs for 10days, 9days, 6days, and 6days, respectively. Cytotoxicity assays were established using the CellTiter-Go assay kit (CTG).
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062

Experiment 1 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.6 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast adenocarcinoma	MDA-MB-231 cells		CVCL_0062
Experiment 2 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.37 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Ovarian serous cystadenocarcinoma	SK-OV-3 cells		CVCL_0532
Experiment 3 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	5.9 ng/mL	Low HER2 expression (HER2+)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Gastric tubular adenocarcinoma	NCI-N87 cells		CVCL_1603
Experiment 4 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	36.1 ng/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Breast ductal carcinoma	JIMT-1 cells		CVCL_2077
Experiment 5 Reporting the Activity Date of This ADC					[52]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	> 10 ug/mL	Negative expression (HER2-)
Method Description	The cytotoxicity of the HER2-targeting ADCs was examined in vitro. Every cell line after treatment for 144h with doses ranging from 0.01 to 10, 000 ng/mL. Results are meanSEM of three replicate experiments.
In Vitro Model	Invasive breast carcinoma	MCF-7 cells		CVCL_0031

Experiment 1 Reporting the Activity Date of This ADC					[60]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	1.09 ng/mL	High TIM-3 expression (TIM-3 +++)
Method Description	EoL-1, EoL-1/hTIM-3 and Kasumi-3 cells were incubated with increasing concentrations of KK2845 or KM8047-SG3249 in RPMI1640 medium supplemented with 10 vol% (for EoL-1 and EoL-1/hTIM-3 cells) or 20 vol% (for Kasumi-3 cells) heat-inactivated fetal bovine serum, 20 vol% heat-inactivated human serum (Sigma), and a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin at 37 °C for 4 days. After incubation, the cells were treated with Cell Counting Kit-8 (CCK-8, Dojindo Laboratories), and the absorbance was measured using a Multiskan Ascent device (Thermo Fisher Scientific, Ascent Software: version 2.6). Primary AML cells were incubated with increasing concentrations of KM8047-SG3249, KK2845, or CD33-ADC in IMDM medium (Thermo Fisher Scientific) supplemented with 20 vol% heat-inactivated human serum, a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin, 25 ng/mL hIL-3 (Miltenyi Biotec), 25 ng/mL hSCF (Peprotech), 25 ng/mL hGM-CSF (R&D), and 25 ng/mL hG-CSF (R&D) at 37 °C for 4 days. After incubation, the cells were stained by anti-CD45 antibody-FITC (BD Pharmingen, HI30 clone), anti-CD34 antibody-APC (BD Bioscience, 8G12 clone), anti-CD38 antibody-BV421 (BD Bioscience, HIT2 clone) and 7-amino-actinomycin D (7-AAD, Bio-Rad Laboratories). The number of viable cells in the CD34+ fraction, CD34+CD38- fraction, or CD34- fraction in primary AML cells was counted by flow cytometry (FACSVerse, software program: BD FACSUITE-V1.0.5).    Click to Show/Hide
In Vitro Model	Chronic eosinophilic leukemia, not otherwise specified,Chronic eosinophilic leukemia	EoL-1/hTIM-3 cells		CVCL_0258
Experiment 2 Reporting the Activity Date of This ADC					[60]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	49.58 ng/mL	Low TIM-3 expression (TIM-3+)
Method Description	EoL-1, EoL-1/hTIM-3 and Kasumi-3 cells were incubated with increasing concentrations of KK2845 or KM8047-SG3249 in RPMI1640 medium supplemented with 10 vol% (for EoL-1 and EoL-1/hTIM-3 cells) or 20 vol% (for Kasumi-3 cells) heat-inactivated fetal bovine serum, 20 vol% heat-inactivated human serum (Sigma), and a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin at 37 °C for 4 days. After incubation, the cells were treated with Cell Counting Kit-8 (CCK-8, Dojindo Laboratories), and the absorbance was measured using a Multiskan Ascent device (Thermo Fisher Scientific, Ascent Software: version 2.6). Primary AML cells were incubated with increasing concentrations of KM8047-SG3249, KK2845, or CD33-ADC in IMDM medium (Thermo Fisher Scientific) supplemented with 20 vol% heat-inactivated human serum, a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin, 25 ng/mL hIL-3 (Miltenyi Biotec), 25 ng/mL hSCF (Peprotech), 25 ng/mL hGM-CSF (R&D), and 25 ng/mL hG-CSF (R&D) at 37 °C for 4 days. After incubation, the cells were stained by anti-CD45 antibody-FITC (BD Pharmingen, HI30 clone), anti-CD34 antibody-APC (BD Bioscience, 8G12 clone), anti-CD38 antibody-BV421 (BD Bioscience, HIT2 clone) and 7-amino-actinomycin D (7-AAD, Bio-Rad Laboratories). The number of viable cells in the CD34+ fraction, CD34+CD38- fraction, or CD34- fraction in primary AML cells was counted by flow cytometry (FACSVerse, software program: BD FACSUITE-V1.0.5).    Click to Show/Hide
In Vitro Model	Adult acute myeloid leukemia	Kasumi-3 cells		CVCL_0612
Experiment 3 Reporting the Activity Date of This ADC					[60]
Efficacy Data	Half Maximal inhibitory Concentration (lC50)	553.7 ng/mL	Low TIM-3 expression (TIM-3+)
Method Description	EoL-1, EoL-1/hTIM-3 and Kasumi-3 cells were incubated with increasing concentrations of KK2845 or KM8047-SG3249 in RPMI1640 medium supplemented with 10 vol% (for EoL-1 and EoL-1/hTIM-3 cells) or 20 vol% (for Kasumi-3 cells) heat-inactivated fetal bovine serum, 20 vol% heat-inactivated human serum (Sigma), and a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin at 37 °C for 4 days. After incubation, the cells were treated with Cell Counting Kit-8 (CCK-8, Dojindo Laboratories), and the absorbance was measured using a Multiskan Ascent device (Thermo Fisher Scientific, Ascent Software: version 2.6). Primary AML cells were incubated with increasing concentrations of KM8047-SG3249, KK2845, or CD33-ADC in IMDM medium (Thermo Fisher Scientific) supplemented with 20 vol% heat-inactivated human serum, a mixture of 100 U/mL penicillin and 100 ug/mL streptomycin, 25 ng/mL hIL-3 (Miltenyi Biotec), 25 ng/mL hSCF (Peprotech), 25 ng/mL hGM-CSF (R&D), and 25 ng/mL hG-CSF (R&D) at 37 °C for 4 days. After incubation, the cells were stained by anti-CD45 antibody-FITC (BD Pharmingen, HI30 clone), anti-CD34 antibody-APC (BD Bioscience, 8G12 clone), anti-CD38 antibody-BV421 (BD Bioscience, HIT2 clone) and 7-amino-actinomycin D (7-AAD, Bio-Rad Laboratories). The number of viable cells in the CD34+ fraction, CD34+CD38- fraction, or CD34- fraction in primary AML cells was counted by flow cytometry (FACSVerse, software program: BD FACSUITE-V1.0.5).    Click to Show/Hide
In Vitro Model	Chronic eosinophilic leukemia	EoL-1 cells		CVCL_0258

Experiment 1 Reporting the Activity Date of This ADC					[61]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.0265 nM	Positive CD34 expression ( CD34+++/++)
Method Description	Primary human CD34+ cells were purchased from STEMCELL technologies (Vancouver, BC, Canada). The cells were obtained using Institutional Review Board (IRB)-approved consent forms and protocols. The steady-state human bone marrow CD34+ cells (3 donors, STEMCELL technologies) or purified mobilized CD34+ cells from two healthy rhesus macaques were cultured (2500 cells/well in 384-well plate) in serum-free StemSpan SFEM media (45 ul, STEMCELL Technologies) supplemented with 100 ng/ml each of Interleukin 6 (IL-6), fms-related tyrosine kinase 3 ligand (FLT3L), and thrombopoietin (TPO). Escalating doses of CD117-ADC as well as IgG isotype control-conjugated ADC were added (5 ul ADC added to 45 ul cells). After 6 days of culture, the number of viable CD34 + CD90+ cells were evaluated by flow cytometry using 7-Aminoactinomycin D (7-AAD as a viability marker, Biolegend, San Diego, CA, USA), CD34 BV785 (clone 561, BioLegend), and CD90 APC (Clone 5E10, BioLegend) detection antibodies. Cells were acquired on a BD Celesta Instrument and analyzed with FloJo. The EC50 and EC90 values were calculated with GraphPad Prism software.    Click to Show/Hide
In Vitro Model	Normal	Rhesus CD34+ cells		Macaca mulatta
Experiment 2 Reporting the Activity Date of This ADC					[61]
Efficacy Data	Half Maximal Effective Concentration (EC50)	0.0521 nM	Positive CD34 expression ( CD34+++/++)
Method Description	Primary human CD34+ cells were purchased from STEMCELL technologies (Vancouver, BC, Canada). The cells were obtained using Institutional Review Board (IRB)-approved consent forms and protocols. The steady-state human bone marrow CD34+ cells (3 donors, STEMCELL technologies) or purified mobilized CD34+ cells from two healthy rhesus macaques were cultured (2500 cells/well in 384-well plate) in serum-free StemSpan SFEM media (45 ul, STEMCELL Technologies) supplemented with 100 ng/ml each of Interleukin 6 (IL-6), fms-related tyrosine kinase 3 ligand (FLT3L), and thrombopoietin (TPO). Escalating doses of CD117-ADC as well as IgG isotype control-conjugated ADC were added (5 ul ADC added to 45 ul cells). After 6 days of culture, the number of viable CD34 + CD90+ cells were evaluated by flow cytometry using 7-Aminoactinomycin D (7-AAD as a viability marker, Biolegend, San Diego, CA, USA), CD34 BV785 (clone 561, BioLegend), and CD90 APC (Clone 5E10, BioLegend) detection antibodies. Cells were acquired on a BD Celesta Instrument and analyzed with FloJo. The EC50 and EC90 values were calculated with GraphPad Prism software.    Click to Show/Hide
In Vitro Model	.	Human CD34+ cells		Homo sapiens

Ref 1	Loncastuximab tesirine in relapsed or refractory diffuse large B-cell lymphoma (LOTIS-2): a multicentre, open-label, single-arm, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):790-800.
Ref 2	A Phase I Study of ADCT-402 (Loncastuximab Tesirine), a Novel Pyrrolobenzodiazepine-Based Antibody-Drug Conjugate, in Relapsed/Refractory B-Cell Non-Hodgkin Lymphoma. Clin Cancer Res. 2019 Dec 1;25(23):6986-6994.
Ref 3	Final results of a phase 1 study of loncastuximab tesirine in relapsed/refractory B-cell non-Hodgkin lymphoma. Blood. 2021 May 13;137(19):2634-2645.
Ref 4	Loncastuximab tesirine, an anti-CD19 antibody-drug conjugate, in relapsed/refractory B-cell acute lymphoblastic leukemia. Blood Adv. 2020 Feb 11;4(3):449-457.
Ref 5	The AntiCD19 Antibody Drug Immunoconjugate Loncastuximab Achieves Responses in DLBCL Relapsing After AntiCD19 CAR-T Cell Therapy. Clin Lymphoma Myeloma Leuk. 2022 May;22(5):e335-e339.
Ref 6	Study Comparing Rovalpituzumab Tesirine Versus Topotecan in Subjects With Advanced or Metastatic Small Cell Lung Cancer With High Levels of Delta-like Protein 3 (DLL3) and Who Have First Disease Progression During or Following Front-line Platinum-based Chemotherapy (TAHOE)
Ref 7	Rovalpituzumab Tesirine in Delta-Like Protein 3-Expressing Advanced Solid Tumors
Ref 8	A Long-Term Study of Rovalpituzumab Tesirine
Ref 9	A Study of Rovalpituzumab Tesirine (SC16LD6.5) in the Frontline Treatment of Patients With Extensive Stage Small Cell Lung Cancer
Ref 10	A Study of Rovalpituzumab Tesirine to Study Cardiac Ventricular Repolarization in Subjects With Small Cell Lung Cancer
Ref 11	Expanded Access to Rovalpituzumab Tesirine
Ref 12	Rovalpituzumab Tesirine (SC16LD6.5) in Recurrent Small Cell Lung Cancer
Ref 13	Study of Rovalpituzumab Tesirine (SC16LD6.5) for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Delta-Like Protein 3-Expressing Small Cell Lung Cancer
Ref 14	A Study of Rovalpituzumab Tesirine Administered in Combination With Nivolumab and With or Without Ipilimumab for Adults With Extensive-Stage Small Cell Lung Cancer
Ref 15	A Study of Rovalpituzumab Tesirine as Maintenance Therapy Following First- Line Platinum-Based Chemotherapy in Participants With Extensive Stage Small Cell Lung Cancer (MERU)
Ref 16	A Study on the Safety and Tolerability of Rovalpituzumab Tesirine in Japanese Patients With Advanced, Recurrent Small Cell Lung Cancer
Ref 17	Study Evaluating the Safety of Rovalpituzumab Tesirine for Third-Line and Later Treatment of Subjects With Relapsed or Refractory Small Cell Lung Cancer
Ref 18	A Study of Budigalimab (ABBV-181) in Participants With Advanced Solid Tumors
Ref 19	Rovalpituzumab Tesirine as a Maintenance Therapy After First-Line Platinum-Based Chemotherapy in Patients With Extensive-Stage-SCLC: Results From the Phase 3 MERU Study. J Thorac Oncol. 2021 Sep;16(9):1570-1581.
Ref 20	Efficacy and Safety of Rovalpituzumab Tesirine in Third-Line and Beyond Patients with DLL3-Expressing, Relapsed/Refractory Small-Cell Lung Cancer: Results From the Phase II TRINITY Study. Clin Cancer Res. 2019 Dec 1;25(23):6958-6966.
Ref 21	A phase I/II study of rovalpituzumab tesirine in delta-like 3-expressing advanced solid tumors. NPJ Precis Oncol. 2021 Aug 5;5(1):74.
Ref 22	Safety, pharmacokinetics, and efficacy of budigalimab with rovalpituzumab tesirine in patients with small cell lung cancer. Cancer Treat Res Commun. 2021;28:100405.
Ref 23	A Phase 1 Study Evaluating Rovalpituzumab Tesirine in Frontline Treatment of Patients With Extensive-Stage SCLC. J Thorac Oncol. 2021 Sep;16(9):1582-1588.
Ref 24	Evaluation of the DLL3-targeting antibody-drug conjugate rovalpituzumab tesirine in preclinical models of neuroblastoma. Cancer Res Commun. 2022 Jul;2(7):616-623.
Ref 25	Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma
Ref 26	Study of ADCT-301 in Patients With Relapsed or Refractory Hodgkin and Non-Hodgkin Lymphoma
Ref 27	Study of ADCT-301 in Patients With Selected Advanced Solid Tumors
Ref 28	ADCT-301 in Patients With R/R AML, MDS, or MDS/MPN
Ref 29	Study of ADCT-301 in Patients With Relapsed/Refractory CD25-positive Acute Myeloid Leukemia (AML) or CD25-positive Acute Lymphoblastic Leukemia (ALL)
Ref 30	Camidanlumab tesirine in patients with relapsed or refractory lymphoma: a phase 1, open-label, multicentre, dose-escalation, dose-expansion study. Lancet Haematol. 2021 Jun;8(6):e433-e445.
Ref 31	Camidanlumab tesirine, an antibody-drug conjugate, in relapsed/refractory CD25-positive acute myeloid leukemia or acute lymphoblastic leukemia: A phase I study. Leuk Res. 2020 Aug;95:106385.
Ref 32	Exposure-response analysis of Camidanlumab tesirine in patients with relapsed or refractory classical Hodgkin lymphoma and non-Hodgkin lymphoma. Cancer Chemother Pharmacol. 2023 Jan;91(1):1-12.
Ref 33	ADCT-301, a Pyrrolobenzodiazepine (PBD) Dimer-Containing Antibody-Drug Conjugate (ADC) Targeting CD25-Expressing Hematological Malignancies. Mol Cancer Ther. 2016 Nov;15(11):2709-2721.
Ref 34	ADCT-602 in Treating Patients with Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
Ref 35	A Phase I/II Study to Evaluate the Safety and Anti-Tumor Activity of ADCT-602 Targeting CD22 in Patients With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia, NCT03698552
Ref 36	A Phase 1 Trial of Adct-602, a CD22 Targeting Antibody Drug Conjugate Bound to PBD Toxin in Adult Patients with Relapsed or Refractory CD22+ B-Cell Acute Lymphoblastic Leukemia. Blood (2021) 138 (Supplement 1): 1237.
Ref 37	Adct-602, a CD22 Targeting Antibody Drug Conjugate Bound to PBD Toxin in Adult Patients with Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia: A Phase 1 Trial. Blood (2022) 140 (Supplement 1): 521522.
Ref 38	A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-901 in Participants With Selected Advanced Solid Tumors
Ref 39	A Phase 1, Open Label, First-in-human Study of TR1801-ADC, an Antibody Drug Conjugate (ADC), in Patients With Select Solid Tumors Expressing c-Met
Ref 40	TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors. Mol Oncol. 2020 Jan;14(1):54-68.
Ref 41	A Phase 1/1b Study of MEDI3726 in Adults Subjects With Metastatic Castration Resistant Prostate Cancer
Ref 42	Study of ADCT-502 in Patients With Advanced Solid Tumors Withhuman Epidermal Growth Factor Receptor-2 (HER2) Expression
Ref 43	MEDI2228 in Subjects With Relapsed/Refractory Multiple Myeloma
Ref 44	A Multiple Ascending Dose Study of MEDI7247 in Patients With Selected Relapsed/?Refractory Hematological Malignancies
Ref 45	A Multiple Ascending Dose Study of MEDI7247 in Advanced or Metastatic Solid Tumors
Ref 46	A Phase 1, Open-Label, Dose-Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of ADCT-502 in Patients With Advanced Solid Tumors With HER2 Expression
Ref 47	Phase 1, First-in-Human Study of MEDI2228, a BCMA-Targeted ADC in Patients with Relapsed/Refractory Multiple Myeloma. Blood (2020) 136 (Supplement 1): 2627.
Ref 48	Phase I Study of MEDI3726: A Prostate-Specific Membrane Antigen-Targeted Antibody-Drug Conjugate, in Patients with mCRPC after Failure of Abiraterone or Enzalutamide. Clin Cancer Res. 2021 Jul 1;27(13):3602-3609.
Ref 49	CMB-401
Ref 50	BCMA-Specific ADC MEDI2228 and Daratumumab Induce Synergistic Myeloma Cytotoxicity via IFN-Driven Immune Responses and Enhanced CD38 Expression. Clin Cancer Res. 2021 Oct 1;27(19):5376-5388.
Ref 51	A novel BCMA PBD-ADC with ATM/ATR/WEE1 inhibitors or bortezomib induce synergistic lethality in multiple myeloma. Leukemia. 2020 Aug;34(8):2150-2162.
Ref 52	Synthesis and evaluation of pyrrolobenzodiazepine dimer antibody-drug conjugates with dual -glucuronide and dipeptide triggers. Eur J Med Chem. 2019 Oct 1;179:591-607.
Ref 53	Design and characterization of homogenous antibody-drug conjugates with a drug-to-antibody ratio of one prepared using an engineered antibody and a dual-maleimide pyrrolobenzodiazepine dimer. MAbs. 2019 Apr;11(3):500-515.
Ref 54	Improved Therapeutic Window in BRCA-mutant Tumors with Antibody-linked Pyrrolobenzodiazepine Dimers with and without PARP Inhibition. Mol Cancer Ther. 2019 Jan;18(1):89-99. doi: 10.1158/1535-7163.MCT-18-0314. Epub 2018 Oct 23.
Ref 55	Tumour-associated macrophages process drug and radio-conjugates of the dead tumour cell-targeting APOMAB antibody. J Control Release. 2020 Nov 10;327:779-787. doi: 10.1016/j.jconrel.2020.09.027.
Ref 56	TR1801-ADC: a highly potent cMet antibody-drug conjugate with high activity in patient-derived xenograft models of solid tumors. Mol Oncol. 2020 Jan;14(1):54-68. doi: 10.1002/1878-0261.12600. Epub 2019 Dec 3.
Ref 57	Design and Synthesis of Tesirine, a Clinical Antibody-Drug Conjugate Pyrrolobenzodiazepine Dimer Payload. ACS Med Chem Lett. 2016 May 24;7(11):983-987.
Ref 58	Antibody drug conjugates, targeting cancer-expressed EGFR, exhibit potent and specific antitumor activity. Biomed Pharmacother. 2023 Jan;157:114047.
Ref 59	Synthesis and evaluation of highly releasable and structurally stable antibody-SN-38-conjugates. Drug Deliv. 2021 Dec;28(1):2603-2617.
Ref 60	KK2845, a PBD dimer-containing antibody-drug conjugate targeting TIM-3-expressing AML
Ref 61	Fertility-preserving myeloablative conditioning using single-dose CD117 antibody-drug conjugate in a rhesus gene therapy model