Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0LQZSE
ADC Name	Naratuximab emtansine
Synonyms	naratuximab emtansine; IMGN529; Debio 1562 Click to Show/Hide
Organization	ImmunoGen (Top20 MNC) (Originator) (No Rights);Debiopharm
Drug Status	Phase 2 (discontinued)
Drug-to-Antibody Ratio	3~4
Structure
		2D MOL
Antibody Name	Naratuximab		Antibody Info
Antigen Name	Leukocyte antigen CD37 (CD37)		Antigen Info
Payload Name	DM1		Payload Info
Therapeutic Target	Microtubule (MT)		Target Info
Linker Name	Succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC)		Linker Info
Conjugate Type	Random Lysines
Combination Type	emtansine
Special Approval(s)	Orphan drug (FDA)

The indication landscape of This ADC(2027 Update)

The clinical trial pipeline of This ADC(2027 Update)

Indication

Phase 1

Phase 1/2

Phase 2

Phase 2/3

Phase 3

New Drug Application

Approved

Chronic lymphocytic leukemia

1 Trials

Trial ID
NCT01534715

Diffuse large b-cell lymphoma

1 Trials

Trial ID
NCT01534715

Follicular lymphoma

1 Trials

Trial ID
NCT01534715

Mantle cell lymphoma

1 Trials

Trial ID
NCT01534715

Unspecific non-hodgkin lymphoma

1 Trials

Trial ID
NCT01534715

General Information of The ADMET Data Related to This ADC(2027 Update)

Absorption

Click To Hide/Show 16 Absorption Data Related to This Level

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (C_max)	2.3	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	3.9	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	9.1	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	13.8	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	20.9	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	24.9	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	36	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg. Click to Show/Hide	[1]
Maximum Observed Concentration (C_max)	53.5	ug/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	14.6	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	63.7	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	238.3	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	529.5	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1174	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1282	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1822	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	2525	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg, AUCinf. Click to Show/Hide	[1]

Distribution

Click To Hide/Show 16 Distribution Data Related to This Level

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	14.6	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	63.7	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	238.3	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	529.5	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1174	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1282	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1822	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	2525	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Volume of Distribution (V_d)	5.1	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	3.8	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	4.8	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	2.6	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	4	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	2.7	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	2.9	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg. Click to Show/Hide	[1]
Volume of Distribution (V_d)	2.8	L	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg. Click to Show/Hide	[1]

Metabolism

Click To Hide/Show 8 Metabolism Data Related to This Level

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	14.6	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	63.7	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	238.3	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	529.5	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1174	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1282	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1822	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	2525	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg, AUCinf. Click to Show/Hide	[1]

Excretion

Click To Hide/Show 24 Excretion Data Related to This Level

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	14.6	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	63.7	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	238.3	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	529.5	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1174	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1282	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	1822	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg, AUCinf. Click to Show/Hide	[1]
Area Under the Concentration-Time Curve (AUC)	2525	ug*h/mL	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg, AUCinf. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	4.9	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	9.8	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	21.6	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	20.9	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	39.7	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	30.3	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	24.9	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg. Click to Show/Hide	[1]
Elimination Half-Life (t_1/2)	33.9	h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.8	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.1 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.3	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.2 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.3	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.4 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.2	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.7 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.07	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 0.8 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.07	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.0 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.09	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.4 mg/kg. Click to Show/Hide	[1]
Clearance (CL)	0.07	L/h	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study, Pharmacokinetic parameters Cycle 1, 1.8 mg/kg. Click to Show/Hide	[1]

General Information of The Activity Data Related to This ADC

Identified from the Human Clinical Data

Click To Hide/Show 2 Activity Data Related to This Level

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT01534715	Phase 1	A phase 1, multi-center, open-label study of IMGN529 administered intravenously in adult patients with relapsed or refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia.
Objective Response Rate (ORR)	NCT02564744	PHASE2	A Phase 2 Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin's Lymphoma Click to Show/Hide

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 4 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Tumor Growth Inhibition value (TGI)	≈ 14.5	%	Non-Hodgkin lymphoma cells Chronic lymphocytic leukemia cells	Non-Hodgkin lymphoma Chronic lymphocytic leukemia
Tumor Growth Inhibition value (TGI)	≈ 99	%	Non-Hodgkin lymphoma cells Chronic lymphocytic leukemia cells	Non-Hodgkin lymphoma Chronic lymphocytic leukemia
Tumor Growth Inhibition value (TGI)	100	%	WSU-NHL cells	Diffuse large B-cell lymphoma
Tumor Growth Inhibition value (TGI)	≈ 100	%	Non-Hodgkin lymphoma cells Chronic lymphocytic leukemia cells	Non-Hodgkin lymphoma Chronic lymphocytic leukemia

Revealed Based on the Cell Line Data

Click To Hide/Show 5 Activity Data Related to This Level

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	< 0.1	nM	Granta-519 cells	Mantle cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	< 0.1	nM	DoHH2 cells	Diffuse large B-cell lymphoma germinal center B-cell type
Half Maximal Inhibitory Concentration (IC50)	< 0.1	nM	Farage cells	Diffuse large B-cell lymphoma
Half Maximal Inhibitory Concentration (IC50)	< 0.1	nM	BJAB cells	Burkitt lymphoma
Half Maximal Inhibitory Concentration (IC50)	< 1	nM	JVM-2 cells	Mantle cell lymphoma

Full List of Activity Data of This Antibody-drug Conjugate

Identified from the Human Clinical Data

Click To Hide/Show 2 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[2]
Efficacy Data	Objective Response Rate (ORR)	12.82%	Positive CD38 expression (CD38+++/++)
Patients Enrolled	Lymphoma limited to diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), or marginal zone lymphoma (MZL). Patients were also required to have received at least one prior anti-CD20 based therapeutic regimen, have a life expectancy of greater than 3 months, an Eastern Cooperative Oncology Group Performance status of 2 or lower, and adequate hematological, renal, and hepatic function. Click to Show/Hide
Administration Dosage	Conventional 3+3 dose-escalation design; intravenously once every 3 weeks; from 0.10 to 1.80 mg/kg.
*Related Clinical Trial*
NCT Number	NCT01534715	Clinical Status	Phase 1
Clinical Description	A phase 1, multi-center, open-label study of IMGN529 administered intravenously in adult patients with relapsed or refractory non-Hodgkin lymphoma and chronic lymphocytic leukemia.
Primary Endpoint	A total of five objective responses were observed, resulting in an overall response rate (ORR) of 12.82% (N=39). Four of these (1 complete response [CR] and 3 partial responses [PRs]) occurred in patients with DLBCL, for an ORR of 22% in this lymphoma subset.
Experiment 2 Reporting the Activity Date of This ADC				[4]
Efficacy Data	Objective Response Rate (ORR)	44.70%
Patients Enrolled	Eligible participants had R/R DLBCL, FL, MZL/MALT, or MCL (WHO 2008 criteria) with 1-6 prior therapies (including anti-CD20); relapsed DLBCL patients required ≥24-week response post-first-line or ≥8-week response post-HD-ASCT. Exclusions: CLL/SLL, primary refractory DLBCL (<24-week response), HD-ASCT candidates, active hepatitis, pregnancy, prior anti-CD37 therapy, CNS involvement, cardiac dysfunction, or severe lung disease. Click to Show/Hide
Administration Dosage	As part of escalation, doses of IMGN529 were doubled from 0.1 mg/kg to 0.8 mg/kg before DLTs were observed.
*Related Clinical Trial*
NCT Number	NCT02564744	Clinical Status	PHASE2
Clinical Description	A Phase 2 Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Patients With Relapsed and/or Refractory Diffuse Large B-Cell Lymphoma and Other Forms of Non-Hodgkin's Lymphoma
Primary Endpoint	The study evaluates treatment-emergent adverse events (TEAEs) over 38 months, including clinically significant lab abnormalities (hematology, serum chemistry, urinalysis, coagulation), ECG changes, and vital sign deviations. Secondary outcomes include objective response rate (ORR) based on RECIST criteria (CR: disappearance of target lesions; PR: ≥50% tumor reduction) assessed until disease progression or new therapy initiation. Click to Show/Hide
Other Endpoint	Key pharmacokinetic parameters (Cmax, AUC0-t, AUC0-inf, t1/2, CL, Vss, Tmax) for Debio 1562 and rituximab were measured across cycles (21-day intervals) up to 37 months. Efficacy endpoints included PFS (time to progression/death), TTR (time to first response), DOR (response duration), and OS (time to death), with PD defined as new lesions, >50% tumor growth, or nodal enlargement >1.5 cm. Anti-drug antibodies (ADA) against Debio 1562 were monitored. Click to Show/Hide

Discovered Using Cell Line-derived Xenograft Model

Click To Hide/Show 4 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 14.50%	Positive CD38 expression (CD38+++/++)
Method Description	IMGN529 induces efficient tumor cell killing in cell line-derived models B-cell NHL of cells with lower CD27 expression, dosed at 2.5 ug/kg , 2 qw3.
In Vivo Model	CD37-positive NHL and CLL model
In Vitro Model	Non-Hodgkin lymphoma	Non-Hodgkin lymphoma cells		Homo sapiens
	Chronic lymphocytic leukemia	Chronic lymphocytic leukemia cells		Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 99%	Positive CD38 expression (CD38+++/++)
Method Description	IMGN529 induces efficient tumor cell killing in cell line-derived models B-cell NHL of cells with lower CD27 expression, dosed at 5 ug/kg , 2 qw3.
In Vivo Model	CD37-positive NHL and CLL model
In Vitro Model	Non-Hodgkin lymphoma	Non-Hodgkin lymphoma cells		Homo sapiens
	Chronic lymphocytic leukemia	Chronic lymphocytic leukemia cells		Homo sapiens
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	100%	Positive CD38 expression (CD38+++/++)
Method Description	The inhibitory activity of SGN-LIV1A against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 1 day.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Diffuse large B-cell lymphoma	WSU-NHL cells		CVCL_1793
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Tumor Growth Inhibition value (TGI)	≈ 100%	Positive CD38 expression (CD38+++/++)
Method Description	IMGN529 induces efficient tumor cell killing in cell line-derived models B-cell NHL of cells with lower CD27 expression, dosed at 10 ug/kg , 2 qw3.
In Vivo Model	CD37-positive NHL and CLL model
In Vitro Model	Non-Hodgkin lymphoma	Non-Hodgkin lymphoma cells		Homo sapiens
	Chronic lymphocytic leukemia	Chronic lymphocytic leukemia cells		Homo sapiens

Revealed Based on the Cell Line Data

Click To Hide/Show 5 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 0.1 nM
Method Description	In vitro cytotoxicity was measured by incubating 5000 target cells with indicated agents in complete RPMI-1640 media for 5 days at 37°C. The viability of remaining cells was determined by a colorimetric WST-11 assay.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Mantle cell lymphoma	Granta-519 cells		CVCL_1818
Experiment 2 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 0.1 nM
Method Description	In vitro cytotoxicity was measured by incubating 5000 target cells with indicated agents in complete RPMI-1640 media for 5 days at 37°C. The viability of remaining cells was determined by a colorimetric WST-10 assay.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Diffuse large B-cell lymphoma germinal center B-cell type	DoHH2 cells		CVCL_1179
Experiment 3 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 0.1 nM	Positive CD38 expression (CD38+++/++)
Method Description	In vitro cytotoxicity was measured by incubating 5000 target cells with indicated agents in complete RPMI-1640 media for 5 days at 37°C. The viability of remaining cells was determined by a colorimetric WST-9 assay.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Diffuse large B-cell lymphoma	Farage cells		CVCL_3302
Experiment 4 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 0.1 nM
Method Description	In vitro cytotoxicity was measured by incubating 5000 target cells with indicated agents in complete RPMI-1640 media for 5 days at 37°C. The viability of remaining cells was determined by a colorimetric WST-8 assay.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Burkitt lymphoma	BJAB cells		CVCL_5711
Experiment 5 Reporting the Activity Date of This ADC					[3]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	< 1 nM
Method Description	In vitro cytotoxicity was measured by incubating 5000 target cells with indicated agents in complete RPMI-1640 media for 5 days at 37°C. The viability of remaining cells was determined by a colorimetric WST-12 assay.
In Vivo Model	DoHH2 CDX model
In Vitro Model	Mantle cell lymphoma	JVM-2 cells		CVCL_1319

References

Ref 1	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study
Ref 2	Safety, tolerability, and preliminary activity of IMGN529, a CD37-targeted antibody-drug conjugate, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: a dose-escalation, phase I study. Invest New Drugs. 2018 Oct;36(5):869-876.
Ref 3	A novel anti-CD37 antibody-drug conjugate with multiple anti-tumor mechanisms for the treatment of B-cell malignancies. Blood. 2013 Nov 14;122(20):3500-10.
Ref 4	Study to Evaluate the Efficacy and Tolerability of Debio 1562 in Combination With Rituximab in Participants With Relapsed and/or Refractory DLBCL and Other Forms of NHL

Antibody-drug Conjugate Information

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Correspondence

Prof. Feng ZHU (zhufeng@zju.edu.cn)

Prof. Xiaowu DONG (dongxw@zju.edu.cn)

Prof. Luo FANG (fangluo@zjcc.org.cn)