Antibody-drug Conjugate Information

General Information of This Antibody-drug Conjugate (ADC)

ADC ID	DRG0JBKMD
ADC Name	Labetuzumab govitecan
Synonyms	HMN-14-SN38; IMMU-130; Anti-carcinoembryonic antigen monoclonal antibody; Anti-CEA monoclonal antibody; anti-CEACAM5-SN38; hMN-14-SN38 antibody-drug conjugate; Labetuzumab-SN38 conjugate; SN38-labetuzumab conjugate Click to Show/Hide
Organization	Immunomedics, Inc.; IBC Pharmaceuticals, Inc.; Gilead Sciences, Inc.
Drug Status	Phase 2
Indication	In total 4 Indication(s) Colorectal cancer [ICD11:2B91] Phase 2 Breast cancer [ICD11:2C60-2C65] Terminated in phase 2 Colon cancer [ICD11:2B90] Terminated in phase 2 Rectal cancer [ICD11:2B92] Terminated in phase 2
Drug-to-Antibody Ratio	7.6
Structure
	3D MOL	2D MOL
Antibody Name	Labetuzumab		Antibody Info
Antigen Name	Carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5)		Antigen Info
Payload Name	Active metabolite of irinotecan SN38		Payload Info
Therapeutic Target	DNA topoisomerase 1 (TOP1)		Target Info
Linker Name	CL2A		Linker Info
Conjugate Type	Random conjugation through reduced inter-chain cysteines.
Combination Type	Govitecan
Puchem SID	472406400 , 319421487 , 481716804 , 249820412 , 385746810 , 481987975 , 312467773 , 481559506 , 249565932 , 347828592 , 480403120
Drugbank ID	DB12331
TTD ID	D03RDS
ChEBI ID	CHEMBL3544923

General Information of The Activity Data Related to This ADC

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
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.

Revealed Based on the Cell Line Data

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

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

Full List of Activity Data of This Antibody-drug Conjugate

Identified from the Human Clinical Data

Click To Hide/Show 1 Activity Data Related to This Level

Experiment 1 Reporting the Activity Date of This ADC				[1]
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.

Revealed Based on the Cell Line Data

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

Experiment 1 Reporting the Activity Date of This ADC				[2]
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				[2]
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				[2]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	140.00 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				[2]
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

References

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. J Clin Oncol. 2017 Oct 10;35(29):3338-3346.
Ref 2	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.