ADC ID	DRG0IYBRT
ADC Name	Epratuzumab-cys-tesirine
Synonyms	ADCT-602; epratuzumab-cys-tesirine; hLL2-cys-PBD; hLL2-PBD    Click to Show/Hide
Organization	ADC Therapeutics (Originator);Overland Pharmaceuticals
Drug Status	Phase 1/2 (discontinued)
Drug-to-Antibody Ratio	1.74
Structure
				2D MOL
Antibody Name	Epratuzumab					Antibody Info
Antigen Name	B-cell receptor CD22 (CD22)					Antigen Info
Payload Name	SG3199 (SC-DR002)					Payload Info
Therapeutic Target	Human deoxyribonucleic acid (hDNA)					Target Info
Linker Name	Mal-PEG8-Val-Ala-PABC					Linker Info
Conjugate Type	Reactive Cysteines
Combination Type	tesirine

Standard Type	Value	Units	Description	Reference
Time to Maximum Concentration (Tmax)	1	h	Assessment of ADCT-602 PK in rats.	[1]
Maximum Observed Concentration (Cmax)	34234	ng/mL	Assessment of ADCT-602 PK in rats.	[1]
Time to Maximum Concentration (Tmax)	0.5	h	Assessment of ADCT-602 PK in cynomolgus monkeys.	[1]
Maximum Observed Concentration (Cmax)	15289	ng/mL	Assessment of ADCT-602 PK in cynomolgus monkeys.	[1]

Standard Type	Value	Units	Description	Reference
Time of Last Quantifiable Concentration (Tlast)	480	h	Assessment of ADCT-602 PK in rats.	[1]
Last Quantifiable Concentration (Clast)	2185	ng/mL	Assessment of ADCT-602 PK in rats.	[1]
Elimination Half-Life (t1/2)	7.8	h	Assessment of ADCT-602 PK in rats.	[1]
Time of Last Quantifiable Concentration (Tlast)	504	h	Assessment of ADCT-602 PK in cynomolgus monkeys.	[1]
Last Quantifiable Concentration (Clast)	160	ng/mL	Assessment of ADCT-602 PK in cynomolgus monkeys.	[1]
Elimination Half-Life (t1/2)	4.5	h	Assessment of ADCT-602 PK in cynomolgus monkeys.	[1]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT03698552	PHASE1|||PHASE2	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
Undisclosed	NCT03698552	Phase 1	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.
Undisclosed	NCT03698552	Phase 1	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.
Undisclosed	NCT03698552	Phase 1	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 1 Reporting the Activity Date of This ADC					[2]
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					[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.
Experiment 3 Reporting the Activity Date of This ADC					[4]
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					[5]
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

Ref 1	ADCT-602, a Novel PBD Dimer-containing Antibody-Drug Conjugate for Treating CD22-positive Hematologic Malignancies
Ref 2	ADCT-602 in Treating Patients with Recurrent or Refractory B-cell Acute Lymphoblastic Leukemia
Ref 3	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 4	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 5	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.