ADC ID	DRG0JBKMD
ADC Name	Labetuzumab govitecan
Synonyms	labetuzumab govitecan; IMMU-130; hMN-14-SN38    Click to Show/Hide
Organization	Immunomedics (Top20 MNC) (Originator)
Drug Status	Phase 2 (discontinued)
Drug-to-Antibody Ratio	7.6~7.8
Structure
				2D MOL
Antibody Name	Labetuzumab					Antibody Info
Antigen Name	Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)					Antigen Info
Payload Name	SN-38					Payload Info
Therapeutic Target	DNA topoisomerase 1 (TOP1)					Target Info
Linker Name	CL2A					Linker Info
Conjugate Type	Random Cysteines
Combination Type	govitecan

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	1606	ug*h/mL	PK parameters of 4 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Maximum Observed Concentration (Cmax)	63.7	ug/mL	PK parameters of 4 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2123	ug*h/mL	PK parameters of 6 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Maximum Observed Concentration (Cmax)	115.5	ug/mL	PK parameters of 6 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	4432	ug*h/mL	PK parameters of 9 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Maximum Observed Concentration (Cmax)	128	ug/mL	PK parameters of 9 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	3752	ug*h/mL	PK parameters of 8 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Maximum Observed Concentration (Cmax)	139.7	ug/mL	PK parameters of 8 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2257	ug*h/mL	PK parameters of 10 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Maximum Observed Concentration (Cmax)	152.5	ug/mL	PK parameters of 10 mg/kg Labetuzumab Govitecan.	[1]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	1606	ug*h/mL	PK parameters of 4 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Volume of Distribution (Vd)	55.7±13.4	mL/kg	PK parameters of 4 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2123	ug*h/mL	PK parameters of 6 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Volume of Distribution (Vd)	55.5	mL/kg	PK parameters of 6 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	4432	ug*h/mL	PK parameters of 9 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Volume of Distribution (Vd)	29.6	mL/kg	PK parameters of 9 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	3752	ug*h/mL	PK parameters of 8 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Volume of Distribution (Vd)	45.1	mL/kg	PK parameters of 8 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2257	ug*h/mL	PK parameters of 10 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Volume of Distribution (Vd)	74.1	mL/kg	PK parameters of 10 mg/kg Labetuzumab Govitecan.	[1]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	1606	ug*h/mL	PK parameters of 4 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	2123	ug*h/mL	PK parameters of 6 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	4432	ug*h/mL	PK parameters of 9 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	3752	ug*h/mL	PK parameters of 8 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Area Under the Concentration-Time Curve (AUC)	2257	ug*h/mL	PK parameters of 10 mg/kg Labetuzumab Govitecan, AUClast.	[1]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	14.9	h	PK parameters of 4 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	1606	ug*h/mL	PK parameters of 4 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Clearance (CL)	2.6	mL/h/kg	PK parameters of 4 mg/kg Labetuzumab Govitecan.	[1]
Elimination Half-Life (t1/2)	14	h	PK parameters of 6 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2123	ug*h/mL	PK parameters of 6 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Clearance (CL)	2.7	mL/h/kg	PK parameters of 6 mg/kg Labetuzumab Govitecan.	[1]
Elimination Half-Life (t1/2)	10.2	h	PK parameters of 9 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	4432	ug*h/mL	PK parameters of 9 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Clearance (CL)	2	mL/h/kg	PK parameters of 9 mg/kg Labetuzumab Govitecan.	[1]
Elimination Half-Life (t1/2)	13.6	h	PK parameters of 8 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	3752	ug*h/mL	PK parameters of 8 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Clearance (CL)	1.9	mL/h/kg	PK parameters of 8 mg/kg Labetuzumab Govitecan.	[1]
Elimination Half-Life (t1/2)	16.8	h	PK parameters of 10 mg/kg Labetuzumab Govitecan.	[1]
Area Under the Concentration-Time Curve (AUC)	2257	ug*h/mL	PK parameters of 10 mg/kg Labetuzumab Govitecan, AUClast.	[1]
Clearance (CL)	3.1	mL/h/kg	PK parameters of 10 mg/kg Labetuzumab Govitecan.	[1]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Undisclosed	NCT01605318	PHASE1|||PHASE2	A Phase I/II Study of Once or Twice Weekly IMMU-130 (hMN-14-SN38, Antibody-Drug Conjugate) in Patients With Colorectal Cancer
Undisclosed	NCT01270698	PHASE1	A Phase I Study of IMMU-130 (hMN-14-SN38 Antibody Drug Conjugate) in Patients With Colorectal Cancer.
Undisclosed	NCT01915472	PHASE2	A Phase II Study of IMMU 130 (hMN-14-SN38 Antibody Drug Conjugate) in Patients With Metastatic Colorectal Cancer
Undisclosed	NCT01605318	Phase 1	A phase 1/2 study of once or twice weekly IMMU-130 (hMN-14-SN38, antibody-drug conjugate) in patients with colorectal cancer.

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	1.23	nM	22RV1 cells	Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50)	4.04	nM	DU145 cells	Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50)	140	nM	MSKCC EF1 cells	Prostate cancer
Half Maximal Inhibitory Concentration (IC50)	3.32	uM	NCI-H660 cells	Prostate small cell carcinoma

Experiment 1 Reporting the Activity Date of This ADC					[2]
Patients Enrolled	Eligible participants must have metastatic colorectal adenocarcinoma (prior irinotecan-treated, ECOG 0-1, CEA >5 ng/mL, measurable disease) with adequate organ function. Exclusions include pregnancy, active CNS metastases, bulky disease (>10 cm), HIV/HBV/HCV positivity, significant cardiac/respiratory disease, or concurrent conditions impairing study compliance. Prior malignancies require ≥3-year disease-free interval (exceptions: non-melanoma skin/cervical cancers).    Click to Show/Hide
Administration Dosage	.
Related Clinical Trial
NCT Number	NCT01605318	Clinical Status	PHASE1|||PHASE2
Clinical Description	A Phase I/II Study of Once or Twice Weekly IMMU-130 (hMN-14-SN38, Antibody-Drug Conjugate) in Patients With Colorectal Cancer
Primary Endpoint	The study assesses the percentage of participants experiencing adverse events (AEs), serious AEs (SAEs), and laboratory abnormalities from the first dose until approximately 2 years post-treatment or disease progression.
Other Endpoint	Key efficacy parameters include duration of response (DOR; time from PR/CR to PD/death), progression-free survival (PFS; treatment start to PD/death), time to progression (TTP), overall survival (OS; treatment start to death), and time-to-treatment failure (TTF). CEA serum level changes are monitored longitudinally.
Experiment 2 Reporting the Activity Date of This ADC					[3]
Patients Enrolled	Eligible patients must have metastatic colorectal adenocarcinoma (prior treatment failure, ECOG 0-1, CEA >5 ng/mL, measurable disease) and adequate organ function. Exclusions include pregnancy, active CNS metastases (unless stable post-treatment), CEA >1000 ng/mL (pre-MTD), grade 3 anorexia/vomiting, uncontrolled autoimmune disease (except stable conditions), HIV/HBV/HCV positivity, recent cardiac/respiratory events, or other conditions impairing study compliance. Prior malignancies require ≥3-year disease-free interval (exceptions: non-melanoma skin/cervical cancers).    Click to Show/Hide
Administration Dosage	IMMU-130 will be administered intravenously every 2 weeks for up to 6 months or longer.
Related Clinical Trial
NCT Number	NCT01270698	Clinical Status	PHASE1
Clinical Description	A Phase I Study of IMMU-130 (hMN-14-SN38 Antibody Drug Conjugate) in Patients With Colorectal Cancer.
Primary Endpoint	The primary focus is on evaluating the safety profile of IMMU-130 across different dose levels, with adverse events and overall toxicity monitored during 6 months of treatment and up to 5 years of follow-up.
Other Endpoint	Secondary objectives include assessing pharmacokinetics, immunogenicity, and preliminary efficacy, with CT scans performed every 8-12 weeks during treatment, every 6 months in the 2nd year, and annually up to 5 years thereafter.
Experiment 3 Reporting the Activity Date of This ADC					[4]
Patients Enrolled	Eligible patients include adults ≥18 with histologically confirmed metastatic colorectal adenocarcinoma, prior irinotecan treatment, ECOG 0-1, adequate organ function, and measurable disease. Exclusions cover pregnancy, uncontrolled comorbidities, active infections, recent malignancies, and conditions interfering with study compliance per investigator judgment.    Click to Show/Hide
Administration Dosage	This is a Phase II, open-label study of IMMU-130 administered every 14 days for a period of 24 weeks to patients with metastatic colorectal cancer who have been previously treated with at least one prior irinotecan-containing regimen.
Related Clinical Trial
NCT Number	NCT01915472	Clinical Status	PHASE2
Clinical Description	A Phase II Study of IMMU 130 (hMN-14-SN38 Antibody Drug Conjugate) in Patients With Metastatic Colorectal Cancer
Primary Endpoint	Safety is evaluated across 6 months of treatment and up to 5 years post-treatment, focusing on adverse events and toxicity levels with different doses of IMMU-130.
Other Endpoint	Secondary objectives include analyzing pharmacokinetics and immunogenicity, along with preliminary efficacy assessment via CT scans, measured every 8 weeks during treatment and every 3-6 months during follow-up for up to 5 years.
Experiment 4 Reporting the Activity Date of This ADC					[5]
Patients Enrolled	Relapsed or refractory metastatic colorectal cancer (mCRC) who had received at least one prior irinotecan-containing regimen.
Administration Dosage	Once weekly at 8 and 10 mg/kg, or two times per week at 4 and 6 mg/km on weeks 1 and 2 of 3-week repeated cycles, intravenous.
Related Clinical Trial
NCT Number	NCT01605318	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of once or twice weekly IMMU-130 (hMN-14-SN38, antibody-drug conjugate) in patients with colorectal cancer.
Primary Endpoint	The median PFS for all 86 patients was 3.60 months (95% CI,2.00 months to 4.00 months), with 16.8% (14 of 86) remaining progression free for at least 6 months, including three patients who maintained this status for at least 1 year. The median OS was 6.90 months (95% CI, 5.70 months to 7.80 months), with 24.41% (21 of 86) surviving for at least 1 year, including three patients who survived at least 2 years (one for 3 years).    Click to Show/Hide
Other Endpoint	In the regorafenib subset (n = 23), the median PFS and OS were 3.90 and 6.70 months, respectively.

Experiment 1 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.23 nM
Method Description	The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
In Vitro Model	Prostate carcinoma	22RV1 cells		CVCL_1045
Experiment 2 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	4.04 nM
Method Description	The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
In Vitro Model	Prostate carcinoma	DU145 cells		CVCL_0105
Experiment 3 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	140 nM
Method Description	The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
In Vitro Model	Prostate cancer	MSKCC EF1 cells		Homo sapiens
Experiment 4 Reporting the Activity Date of This ADC					[6]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.32 uM
Method Description	The inhibitory activity of IMMU-130 against cancer cell growth was evaluated in various human cancer cell lines in vitro. The cells were treated 4 days.
In Vitro Model	Prostate small cell carcinoma	NCI-H660 cells		CVCL_1576

Ref 1	Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer
Ref 2	Study of Labetuzumab Govitecan in Participants With Metastatic Colorectal Cancer
Ref 3	Study of IMMU-130 in Patients With Relapsed/Refractory Colorectal Cancer
Ref 4	A Phase II Study of IMMU 130 in Patients With Metastatic Colorectal Cancer
Ref 5	Phase I/II Trial of Labetuzumab Govitecan (Anti-CEACAM5/SN-38 Antibody-Drug Conjugate) in Patients With Refractory or Relapsing Metastatic Colorectal Cancer. J Clin Oncol. 2017 Oct 10;35(29):3338-3346.
Ref 6	Regulation of CEACAM5 and Therapeutic Efficacy of an Anti-CEACAM5-SN38 Antibody-drug Conjugate in Neuroendocrine Prostate Cancer. Clin Cancer Res. 2021 Feb 1;27(3):759-774.