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).

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

Eligible participants were ≥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.

Eligible participants were adults with DLL3-positive (≥1% tumor staining) SCLC progressing after ≥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.

Eligible participants had DLL3-expressing SCLC progressing after ≥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.

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.

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.

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.

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).

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.

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.

Eligible participants were adults (≥18 years) with relapsed/refractory lymphoma (WHO-confirmed), ECOG 0-2, adequate organ function (ANC≥1500/uL, platelets≥75,000/uL, bilirubin≤1.5×ULN), and measurable disease (Lugano 2014). Exclusions included active GVHD, recent transplant (<60 days), autoimmune diseases, uncontrolled comorbidities (e.g., QTc≥450ms), or prior ADCT-301 hypersensitivity. Pregnancy, breastfeeding, or inadequate recovery from prior therapy (non-hematologic toxicity >Grade 1) also excluded participation.

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).

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.

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.

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.

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.

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.

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.

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.

Inclusion: Adults ≥18 with relapsed/refractory AML, MDS, or MDS/MPN post-allogeneic transplant, stable GVHD (grade 1), creatinine clearance ≥60ml/min, liver function within limits, no pregnancy, and immune suppression ≤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.).

Eligibility requires relapsed/refractory CD25+ AML/ALL (WHO criteria), ECOG 0-2, adequate organ function (creatinine ≤1.5mg/dL, ALT/AST ≤2×ULN, bilirubin ≤1.5×ULN), and WBC <15,000/uL. Exclusions include active CNS leukemia, GVHD, recent transplant (≤60 days), HIV/HBV/HCV, QTc ≥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.

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.

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.

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.

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).

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).

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.

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.

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).

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.

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.

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).

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.

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.

Key eligibility: CD22+ (≥20% blasts) B-ALL patients (Ph+ allowed after TKI failure) with ≥5% marrow blasts, ECOG 0-2, adequate organ function (Cr≤1.5mg/dL, LVEF≥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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

In vitro cytotoxicity was determined by incubation of cell lines with serial dilutions of ADCT-601,the nonbinding control ADC,or the free PBD dimer cytotoxin SG3199 for 5-8 days at 37°C in a 5% CO₂-gassed,humidified incubator. ADCT-601 selectively inhibited the growth of a panel of seven AXL-positive human cancer cell lines and two AXL-negative cell lines.

Eligible participants are adults (≥18 years) with locally advanced/metastatic solid tumors (specific sarcoma subtypes, NSCLC, or AXL-amplified tumors) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active CNS metastases (unless treated and stable ≥4 weeks), significant third-space fluid accumulation, recent infections requiring IV therapy, chronic diarrhea (CTCAE Grade 2+), or experimental medication use within 14 days prior to treatment initiation.

As of 04 December 2023, 18 sarcoma patients (15 [83%], soft tissue sarcoma [STS] and 3 [17%] bone sarcoma), unselected for AXL expression, with a median number of 3 prior lines of therapy (1-10), were enrolled in 4 different dose cohorts: 7.5mg, 11mg, 13mg and 15mg. Reasons for treatment discontinuation were disease progression (10 pts [55.6%]), adverse events (3 pts [16.7%]) and consent withdrawal (2 pts [11.1%]). Treatment emergent adverse events (TEAE) were seen in 17 pts (94.4%). Most common TEAE (all grades and relationship [≥20%]) were palmar-plantar erythrodysesthesia syndrome (7 pts [38.9%]); anemia (6 pts [33.3%]); rash maculopapular (5 pts [27.8%]); cheilitis and constipation (4 pts each [22.2%]). TEAE≥grade 3 were seen in 9 pts (50%). Most common TEAE≥grade 3 (≥10%) were GGT increase (2 pts [11.1%]). Two dose limiting toxicities were seen: cheilitis grade 2 and grade 3 at 15mg and 13mg respectively. Cutaneous reactions, all grades, are more prominent in higher doses. Maximum tolerated dose (MTD) has not been established.

Efficacy is measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 2 years. Pharmacokinetic analysis includes serum concentration measurements of ADCT-601 components (total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199) with parameters like Cmax, Tmax, AUC, and half-life, alongside immunogenicity assessment through anti-drug antibody (ADA) responses and titers.

Eligible participants are adults (≥18 years) with locally advanced/metastatic solid tumors (specific sarcoma subtypes, NSCLC, or AXL-amplified tumors) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active CNS metastases (unless treated and stable ≥4 weeks), significant third-space fluid accumulation, recent infections requiring IV therapy, chronic diarrhea (CTCAE Grade 2+), or experimental medication use within 14 days prior to treatment initiation.

As of 04 December 2023, 18 sarcoma patients (15 [83%], soft tissue sarcoma [STS] and 3 [17%] bone sarcoma), unselected for AXL expression, with a median number of 3 prior lines of therapy (1-10), were enrolled in 4 different dose cohorts: 7.5mg, 11mg, 13mg and 15mg. Reasons for treatment discontinuation were disease progression (10 pts [55.6%]), adverse events (3 pts [16.7%]) and consent withdrawal (2 pts [11.1%]). Treatment emergent adverse events (TEAE) were seen in 17 pts (94.4%). Most common TEAE (all grades and relationship [≥20%]) were palmar-plantar erythrodysesthesia syndrome (7 pts [38.9%]); anemia (6 pts [33.3%]); rash maculopapular (5 pts [27.8%]); cheilitis and constipation (4 pts each [22.2%]). TEAE≥grade 3 were seen in 9 pts (50%). Most common TEAE≥grade 3 (≥10%) were GGT increase (2 pts [11.1%]). Two dose limiting toxicities were seen: cheilitis grade 2 and grade 3 at 15mg and 13mg respectively. Cutaneous reactions, all grades, are more prominent in higher doses. Maximum tolerated dose (MTD) has not been established.

Efficacy is measured by overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 2 years. Pharmacokinetic analysis includes serum concentration measurements of ADCT-601 components (total antibody, PBD-conjugated antibody, and unconjugated warhead SG3199) with parameters like Cmax, Tmax, AUC, and half-life, alongside immunogenicity assessment through anti-drug antibody (ADA) responses and titers.

Eligible patients must be ≥18 years with locally advanced/metastatic solid tumors (including breast, colorectal, NSCLC, and ovarian cancers) refractory to standard therapy, measurable disease per RECIST 1.1, ECOG 0-1, and adequate organ function. Key exclusions include active autoimmune/CNS diseases, uncontrolled comorbidities, recent anticancer therapy (<14 days), QTcF >480 ms, pregnancy, or live vaccines. Contraception is required during and for 16 weeks post-treatment.

As of data cutoff (April 12, 2019), 8 pts were treated at doses of 50-100 ug/kg. The median (range) age was 70 (46-77) years. Pathological subtypes enrolled are colorectal cancer (4 pts) and chondrosarcoma, head and neck carcinoma, ovarian carcinoma, and esophageal carcinoma (1 pt each). Six pts had received ≥4 previous lines of therapy. One pt treated at 100 ug/kg had a dose-limiting toxicity of grade 3 hematuria, which resulted in hospitalization and was possibly related to ADCT-601. The most common treatment-emergent adverse events, regardless of relationship to ADCT-601, were abdominal pain, erythema, fatigue, peripheral edema, and maculopapular rash (each occurring in 2 pts). The following 4 pts had undergone disease assessment at data cutoff: 1 pt (chondrosarcoma) had a partial response, 1 pt (head and neck carcinoma) had stable disease, and 2 pts (ovarian carcinoma and esophageal carcinoma) had progressive disease.

The study evaluates safety by assessing dose-limiting toxicities (DLTs) during the first treatment cycle (21-42 days depending on dosing schedule) and determines the maximum tolerated dose (MTD) through monitoring adverse events (AEs), serious adverse events (SAEs), and dose modifications over a 2-year follow-up period with treatment cycles every 3-6 weeks.

Eligible participants must have histologically confirmed neuroendocrine neoplasms or adrenocortical carcinoma (ACC) with measurable disease (RECIST 1.1), prior standard therapy failure, ECOG ≤2, and adequate organ function. Exclusions include recent anticancer treatments (within 4 weeks), active infections, uncontrolled autoimmune diseases, QTcF ≥480 ms, pregnancy, or live vaccines within 30 days. Contraception is required during and post-treatment (9.5 months for females, 6.5 months for males).

Safety evaluations include monitoring AEs through 30 days post-treatment, while efficacy is assessed via overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) over 5 years. Pharmacokinetic (PK) analysis measures PBD-conjugated antibody, total antibody, and unconjugated warhead SG3199 for up to 2 years, alongside immunogenicity testing for anti-drug antibodies (ADAs).

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).

All patients (N = 35) were included in response analyses. Five patients (14.29%) overall achieved a PR per investigator assessment,with no patients achieving a CR. One patient each had a PR in the 0.20 and 0.30 mg/kg Q3W dose groups, and 3 patients in the 0.40 mg/kg Q9W dose group, fourteen (40.00%) patients achieved stable disease as their best overall response,and 5 had no or an non-evaluable posttreatment scan.

Nineteen patients had tumor samples that were able to be assessed for DLL3 expression by immunohistochemistry. DLL3-positive expression by immunohistochemistry (DLL3 >0%) was confirmed in 17 patients; 5 were DLL3 high (75.00% DLL3 positive cells). Of DLL3-positive patients, 2 (11.80%) achieved a PR, including 1 patient in the 0.20 mg/kg Q3W cohort and 1 DLL3-high patient in the 0.40 mg/kg Q9W cohort.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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).

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).

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).