ADC ID	DRG0EKTUN
ADC Name	Sacituzumab govitecan
Brand Name	Trodelvy
Synonyms	sacituzumab govitecan; IMMU-132; hRS7-CL2A-SN-38; sacituzumab govitecan-hziy; Trodelvy; GS-0132    Click to Show/Hide
Organization	Immunomedics (Top20 MNC) (Originator);Seagen (Top20 MNC) (No Rights);Everest Medicines (No Rights)
Drug Status	Approved in 2020
Drug-to-Antibody Ratio	7.6~8
Structure
				2D MOL
Antibody Name	Sacituzumab					Antibody Info
Antigen Name	Tumor-associated calcium signal transducer 2 (TACSTD2); Programmed cell death 1 ligand 1 (PD-L1)					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
Absorption	For sacituzumab govitecan (10 mg/kg), mean Cmax was 243.0±45.6 (ug/mL) and mean AUC was 5,210±1,230 (ug x h/mL). For free SN-38, mean Cmax was 127±60 (ng/mL) and mean AUC was 3.90±1.83 (ug x h/mL).
Distribution	Sacituzumab govitecan has a mean volume of distribution of 0.045 L/kg. The active element, SN-38, is predominantly attached to the IgG component in serum. After administering 10 mg/kg of sacituzumab govitecan, free SN-38 serum levels were measured at 2.3% after 30 minutes and 4.5% after one day.
Metabolism	The metabolism of sacituzumab govitecan has not been extensively studied. The SN-38 moiety is known to undergo O-glucuronidation by UGT1A1, presumably in the liver, and the SN-38 glucuronide metabolite SN-38G is found in the serum of patients undergoing treatment. Sacituzumab govitecan has a mean half-life of 16 hours, while free SN-38 has a mean half-life of 18 hours.
Elimination	Renal elimination of SN-38 is known to be minimal, and it is expected that the fecal route will be the major contributor.
Toxicity	Patients experiencing an overdose are at an increased risk of severe adverse effects such as neutropenia, diarrhea, hypersensitivity, nausea/vomiting, and other systemic effects related to cytotoxic drugs. FDA black box warning: severe neutropenia and diarrhea may occur.
Special Approval(s)	Priority review (FDA); Accelerated approval (FDA); Fast track (FDA); Orphan drug (FDA); Breakthrough therapy (FDA);Priority review (NMPA)

Bystander Killing Effect	Description	Reference
yes	To evaluate the ability of SG to induce a bystander killing effect in a tumor environment where Trop-2 is expressed heterogeneously we tested the ADC activity by admixing SARARK9 (ie, high Trop-2 expression) in vitro with low/negligible Trop-2 expressing cells (i.e., GFP-ARK4 cells) for 72 hrs (cells were incubated with the drugs for 12 hrs as stated in the materials and methods section). A significant increase in cytotoxicity of ARK4 cells was seen when ARK4 and SARARK9 were cultured together and treated with SG when compared to ADC-control-treated co-cultures (p=0.017).    Click to Show/Hide	[5]

Dissocation Constant (Kd)	Binding Target	Description	Reference
0.658±0.140 nM	Trop-2	IMMU-132 Kd is 0.658 ± 0.140 nM.	[5]
0.62±0.14 nM	Trop-2	Summary of BlACORE Ko-analysis for Trop-2 binding.	[5]
191.9±47.6 nM	FcRn	Summary of BlACORE Ko-analysis for FcRn binding.	[5]

Incubation Time	1days	Release	50%	Reference	[5]
Incubation Medium	Serum
Description	During manufacturing, conditions are adjusted to minimize any loss of SN-38 from IMMU-132, with the final lyophilized product consistently having < 1% free SN-38 when reconstituted. However, when placed in serum and held at 37°C, SN-38 is released from the conjugate with a half-life of ~1 day; Levels were largely cleared within 3 days, and SN-38 was released gradually at a rate of about 50% per day    Click to Show/Hide

Standard Type	Value	Units	Description	Reference
Maximum Observed Concentration (Cmax)	239000	ng/mL	Based on population pharmacokinetic analysis, the mean maximum serum concentration (Cmax) of sacituzumab govitecan was 239,000 ng/mL (percent coefficient of variation 11%).	[1]
Area Under the Concentration-Time Curve (AUC)	540000	ng*h/mL	Based on population pharmacokinetic analysis, the area under the serum concentration curve from time zero to 168 h (AUC0-168) was 5,640,000 ng·h/mL (22%).	[1]
Area Under the Concentration-Time Curve (AUC)	4.8±1.9	mg*h/mL	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	5.3±1.4	mg*h/mL	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	1516	ug*h/mL	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Maximum Observed Concentration (Cmax)	133.3	ug/mL	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Maximum Observed Concentration (Cmax)	215000	ng/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg.	[6]
Maximum Observed Concentration (Cmax)	227000	ng/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg.	[6]
Area Under the Concentration-Time Curve (AUC)	536000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Area Under the Concentration-Time Curve (AUC)	519000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Maximum Observed Concentration (Cmax)	239000	ng/mL	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]
Area Under the Concentration-Time Curve (AUC)	5640000	ng*h/mL	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	540000	ng*h/mL	Based on population pharmacokinetic analysis, the area under the serum concentration curve from time zero to 168 h (AUC0-168) was 5,640,000 ng·h/mL (22%).	[1]
Volume of Distribution (Vd)	3.6	L	The steady-state volume of distribution for sacituzumab govitecan was 3.6 L.	[1]
Area Under the Concentration-Time Curve (AUC)	4.8±1.9	mg*h/mL	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	5.3±1.4	mg*h/mL	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Volume of Distribution (Vd)	35.7±12.6	mL/kg	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Volume of Distribution (Vd)	33.8±12.1	mL/kg	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Volume of Distribution (Vd)	3.68	L	Administered to 529 patients with mTNBC or other solid tumors in clinical trials (NCT01631552; NCT02574455).	[2]
Volume of Distribution (Vd)	0.045	L/kg	Administered at 10 mg/kg to patients with mTNBC.	[4]
Area Under the Concentration-Time Curve (AUC)	1516	ug*h/mL	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Area Under the Concentration-Time Curve (AUC)	536000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Area Under the Concentration-Time Curve (AUC)	519000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Volume of Distribution (Vd)	2760	L	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg.	[6]
Volume of Distribution (Vd)	2820	L	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg.	[6]
Area Under the Concentration-Time Curve (AUC)	5640000	ng*h/mL	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]
Volume of Distribution (Vd)	3.6	L	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]

Standard Type	Value	Units	Description	Reference
Area Under the Concentration-Time Curve (AUC)	540000	ng*h/mL	Based on population pharmacokinetic analysis, the area under the serum concentration curve from time zero to 168 h (AUC0-168) was 5,640,000 ng·h/mL (22%).	[1]
Area Under the Concentration-Time Curve (AUC)	4.8±1.9	mg*h/mL	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	5.3±1.4	mg*h/mL	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	1516	ug*h/mL	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Area Under the Concentration-Time Curve (AUC)	536000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Area Under the Concentration-Time Curve (AUC)	519000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Area Under the Concentration-Time Curve (AUC)	5640000	ng*h/mL	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]

Standard Type	Value	Units	Description	Reference
Elimination Half-Life (t1/2)	16	h	Sacituzumab govitecan has a mean half-life of 16 hours, while free SN-38 has a mean half-life of 18 hours.	[1]
Clearance (CL)	0.002	L/h/kg	Sacituzumab govitecan has a clearance rate of 0.002 L/h/kg.	[1]
Area Under the Concentration-Time Curve (AUC)	540000	ng*h/mL	Based on population pharmacokinetic analysis, the area under the serum concentration curve from time zero to 168 h (AUC0-168) was 5,640,000 ng·h/mL (22%).	[1]
Elimination Half-Life (t1/2)	14.4±3.3	h	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Elimination Half-Life (t1/2)	11.7±3.3	h	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	4.8±1.9	mg*h/mL	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Area Under the Concentration-Time Curve (AUC)	5.3±1.4	mg*h/mL	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Clearance (CL)	1.7±0.6	mL/h/kg	Patients who had multiple prior therapies received 8 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Clearance (CL)	2.0±0.6	mL/h/kg	Patients who had multiple prior therapies received 10 mg/kg IMMU-132 on days 1 and 8 of 21-day treatment cycles.	[1]
Clearance (CL)	0.133	L/h	Two-compartment model with body weight-based scaling. Administered to 529 patients with mTNBC or other solid tumors in clinical trials (NCT01631552; NCT02574455).	[2]
Elimination Half-Life (t1/2)	11.7-18.9	h	Half-life of IMMU-132 conjugate and IgG in patients with advanced solid tumors.	[3]
Clearance (CL)	0.002	L/h/kg	Administered at 10 mg/kg to patients with mTNBC and other metastatic cancers.	[4]
Elimination Half-Life (t1/2)	16	h	Administered at 10 mg/kg to patients with mTNBC and other metastatic cancers.	[4]
Elimination Half-Life (t1/2)	11	h	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Area Under the Concentration-Time Curve (AUC)	1516	ug*h/mL	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Clearance (CL)	0.012	mL/h	Pharmacokinetics of IMMU-132 in mice. Naïve nude mice (N = 5) were injected i.v. with 200 ug of IMMU-132	[5]
Elimination Half-Life (t1/2)	16.6	h	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg.	[6]
Elimination Half-Life (t1/2)	15.2	h	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg.	[6]
Area Under the Concentration-Time Curve (AUC)	536000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Area Under the Concentration-Time Curve (AUC)	519000	ng*h/mL	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg area under the serum concentration-time curve from time 0 to 168 hours	[6]
Clearance (CL)	127	L/h	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),8 mg/kg.	[6]
Clearance (CL)	149	L/h	Pharmacokinetic parameters and concentrations of SG in all disease cohorts (pharmacokinetic population),10 mg/kg.	[6]
Area Under the Concentration-Time Curve (AUC)	5640000	ng*h/mL	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]
Elimination Half-Life (t1/2)	16	h	Pharmacokinetics (PK) Profile of Sacituzumab Govitecan	[7]

Standard Type	NCT Number	Clinical Status	Clinical Trial Description
Objective Response Rate (ORR)	NCT03901339	Phase 3	Phase 3 study of sacituzumab govitecan (IMMU-132) versus treatment of physician's choice (tpc) in subjects with hormonal receptor-positive (hr+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC) who have failed at least two prior chemotherapy regimens.    Click to Show/Hide
Objective Response Rate (ORR)	NCT02574455	Phase 3	Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.
Objective Response Rate (ORR)	NCT02574455	Phase 3	An international, multi-center, open-label, randomized, phase 3 trial of sacituzumab govitecan versus treatment of physician choice in patients with metastatic triple-negative breast cancer who received at least two prior treatments.    Click to Show/Hide
Objective Response Rate (ORR)	NCT04454437	Phase 2	A phase IIb, single arm, multicenter trial of sacituzumab govitecan in chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments.
Objective Response Rate (ORR)	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Objective Response Rate (ORR)	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Objective Response Rate (ORR)	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Objective Response Rate (ORR)	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Objective Response Rate (ORR)	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Undisclosed	NCT01631552	Phase 1	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.

Standard Type	Value	Units	Animal Model (No. of PDX)
Half Maximal Inhibitory Concentration (IC50)	2.14	nM	Endometrioma PDX model (PDX: END(K)265)

Standard Type	Value	Units	Cell Line	Disease Model
Half Maximal Inhibitory Concentration (IC50)	0.18-0.26	nM	Primary cervical cancer cells	Primary cervical cancer
Half Maximal Inhibitory Concentration (IC50)	0.6	nM	USPC-ARK-2 cells	Endometrial serous adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.02	nM	COLO 205 cells	Colon adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.44	nM	BxPC-3 cells	Pancreatic ductal adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	1.86	nM	PC-3 cells	Prostate carcinoma
Half Maximal Inhibitory Concentration (IC50)	3.5	nM	Capan-1 cells	Pancreatic ductal adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	3.9	nM	USPC-ARK-2 cells	Endometrial serous adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	7.19	nM	Calu-3 cells	Lung adenocarcinoma
Half Maximal Inhibitory Concentration (IC50)	8.61	nM	SK-MES-1 cells	Lung squamous cell carcinoma

Experiment 1 Reporting the Activity Date of This ADC					[8]
Efficacy Data	Objective Response Rate (ORR)	21%
Patients Enrolled	Patients had histologically locally confirmed measurable HR+/HER2 MBC and 2-4 prior systemic chemotherapy regimens for metastatic disease. (Neo)adjuvant therapy for early-stage disease qualified as one of the required prior chemotherapy regimens if the development of unresectable, locally advanced, or metastatic disease occurred within 12 months of therapy (early relapse). Patients must have previously received at least one taxane, at least one anticancer hormonal treatment, and at least one CDK4/6i.    Click to Show/Hide
Administration Dosage	10 mg/kg intravenously once weekly on day 1 and day 8 every 21 days.
Related Clinical Trial
NCT Number	NCT03901339	Clinical Status	Phase 3
Clinical Description	Phase 3 study of sacituzumab govitecan (IMMU-132) versus treatment of physician's choice (tpc) in subjects with hormonal receptor-positive (hr+) human epidermal growth factor receptor 2 (HER2) negative metastatic breast cancer (MBC) who have failed at least two prior chemotherapy regimens.
Primary Endpoint	PFS=5.50 months.
Other Endpoint	OS=13.90 months.
Experiment 2 Reporting the Activity Date of This ADC					[9]
Efficacy Data	Objective Response Rate (ORR)	31.43%
Patients Enrolled	Patients had metastatic triple-negative breast cancer (mTNBC) that had progressed following 2 prior standard chemotherapy regimens (no upper limit) for unresectable, locally advanced, or metastatic disease, and included a taxane (any setting). Per protocol, patients were also eligible after only one prior regimen in the metastatic setting if their disease recurred within 12 months of completing (neo)adjuvant therapy.    Click to Show/Hide
Administration Dosage	10 mg/kg on days 1 and 8 of 21-day cycles; until progression, unacceptable toxicity, study withdrawal, or death.
Related Clinical Trial
NCT Number	NCT02574455	Clinical Status	Phase 3
Clinical Description	Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer.
Primary Endpoint	PFS=4.60 months for patients without TNBC at initial diagnosis PFS=5.70 months for patients with TNBC at initial diagnosis.
Other Endpoint	ORR=31.43%.
Experiment 3 Reporting the Activity Date of This ADC					[10]
Efficacy Data	Objective Response Rate (ORR)	35%
Patients Enrolled	Patients with metastatic triple-negative breast cancer that was relapsed or refractory to two or more previous standard chemotherapy regimens (no upper limit) for unresectable, locally advanced or metastatic disease; previous therapy had to include a taxane (for any indication). Patients had to have triple-negative breast cancer according to standard American Society of Clinical OncologyCollege of American Pathologists criteria.    Click to Show/Hide
Administration Dosage	Sacituzumab govitecan at a dose of 10 mg per kilogram of body weight intravenously on days 1 and 8 of each 21-day cycle.
Related Clinical Trial
NCT Number	NCT02574455	Clinical Status	Phase 3
Clinical Description	An international, multi-center, open-label, randomized, phase 3 trial of sacituzumab govitecan versus treatment of physician choice in patients with metastatic triple-negative breast cancer who received at least two prior treatments.
Primary Endpoint	Progression-free survival=5.60 months,(95% CI, 4.30-6.30) with sacituzumab govitecan and 1.70 months (95% CI,1.50 to 2.60) with chemotherapy (hazard ratio for disease progression or death, 0.41; 95% CI, 0.32-0.52).
Other Endpoint	The percentage of patients with an objective response was 35.00% with sacituzumab govitecan and 5.00% with chemotherapy.
Experiment 4 Reporting the Activity Date of This ADC					[11]
Efficacy Data	Objective Response Rate (ORR)	38.80%	High TROP2 expression (TROP2+++)
Patients Enrolled	Histologically or cytologically confirmed metastatic triple negative breast cancer (mTNBC); refractory or relapsing after 2 prior standard chemotherapy for unresectable, locally advanced, or metastatic disease, including a taxane (any setting).
Administration Dosage	10 mg/kg intravenously on Days 1 and 8 of each 21-day treatment cycle.
Related Clinical Trial
NCT Number	NCT04454437	Clinical Status	Phase 2
Clinical Description	A phase IIb, single arm, multicenter trial of sacituzumab govitecan in chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments.
Primary Endpoint	Objective response rate=38.80% (95% CI 28.06-50.30), clinical benefit rate=43.80% (95% CI 32.68-55.30).
Other Endpoint	Median PFS=5.55 months (95% CI 4.14-N/A).
Experiment 5 Reporting the Activity Date of This ADC					[12]
Efficacy Data	Objective Response Rate (ORR)	14%
Patients Enrolled	Patients 18 years of age with mSCLC who had relapsed or were refractory to at least one prior standard line of therapy for metastatic disease, and with measurable tumors by CT, were enrolled. They were required to have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and other eligibility as described in the phase I trial (25). Previous therapy had to be completed at least 2 weeks before enrollment.    Click to Show/Hide
Administration Dosage	Either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles.
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Primary Endpoint	OrR=14.00% (17.00% for 10 mg/kg group).
Other Endpoint	The median response duration=5.70 months; the clinical benefit rate (CBR>4 months), 34.00%; median PFS=3.70 months; median OS=7.50 months.
Experiment 6 Reporting the Activity Date of This ADC					[13]
Efficacy Data	Objective Response Rate (ORR)	17.70 22.20 9.10 %
Patients Enrolled	Patients were >18 years of age with metastatic cancer [cervical, clear-cell renal, CRC, epithelial ovarian, endometrial, esophageal, gastric, hepatocellular, CRPC, pancreatic ductal adenocarcinoma, squamous cell head and neck, thyroid, urothelial (UC) cancer; glioblastoma multiforme; mTNBC or non-mTNBC; and SCLC or NSCLC] who had relapsed after or were refractory to at least one prior standard therapeutic regimen.    Click to Show/Hide
Administration Dosage	Intravenous 8, 10, 12, or 18 mg/kg on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity.
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Primary Endpoint	Safety and pharmacokinetic parameters with investigator-evaluated objective response rate.
Other Endpoint	Efficacy endpoints included: ORR, which included both confirmed partial response (PR) and complete response (CR).
Experiment 7 Reporting the Activity Date of This ADC					[14]
Efficacy Data	Objective Response Rate (ORR)	19%
Patients Enrolled	Patients 18 years with mNSCLC who had measurable disease and progressed after at least one line of therapy for stage IV disease were enrolled. Requirements included Eastern Cooperative Oncology Group performance status 0 or 1, adequate bone marrow and hepatic and renal function, and other eligibility criteria as described in the phase I trial. Prior systemic therapy had to be completed at least 4 weeks before enrollment.    Click to Show/Hide
Administration Dosage	Doses of 8 or 10 mg/kg were given on days 1 and 8 of 21-day cycles; intravenously.
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Primary Endpoint	Safety and objective response rate (ORR).
Other Endpoint	Progression-free survival and overall survival.
Experiment 8 Reporting the Activity Date of This ADC					[15]
Efficacy Data	Objective Response Rate (ORR)	30%
Patients Enrolled	Patients 18 years of age who had mTNBC refractory to or relapsed after at least one standard line of therapy since diagnosis and measurable disease by computed tomography scan (or magnetic resonance imaging). patients had an Eastern Cooperative Oncology Group performance status of 0 or 1, adequate bone marrow, hepatic and renal function, and prior toxicities at study entry of grade 1 by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4.03. Patients with brain metastasis were excluded, unless treated and without progression, and were not receiving high-dose corticosteroids for at least 4 weeks.    Click to Show/Hide
Administration Dosage	10 mg/kg starting dose on days 1 and 8 of 21-day repeated cycles; intravenously; eight cycles.
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Primary Endpoint	Safety and objective response rate.
Other Endpoint	Progression-free survival and overall survival.
Experiment 9 Reporting the Activity Date of This ADC					[16]
Efficacy Data	Objective Response Rate (ORR)	33.30%
Patients Enrolled	Metastatic triple-negative breast cancer.
Administration Dosage	10 mg per kilogram intravenously on days 1 and 8 of each 21-day cycle until disease progression or unacceptable toxic effects.
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.
Primary Endpoint	Objective response rate=33.3% (95% confidence interval [CI].
Other Endpoint	The median duration of response=7.70 months (95% CI, 4.90 to 10.08),clinical benefit rate = 45.40%.
Experiment 10 Reporting the Activity Date of This ADC					[17]
Related Clinical Trial
NCT Number	NCT01631552	Clinical Status	Phase 1
Clinical Description	A phase 1/2 study of IMMU-132 (hRS7-SN38 antibody drug conjugate) in patients with epithelial cancer.

Experiment 1 Reporting the Activity Date of This ADC					[18]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	2.14 nM
Method Description	Antibody-dependent cell cytotoxicity (ADCC) against Trop-2-positive and Trop-2-negative EC cell lines was measured in vitro,compared to control ADC (P = 0.014 and P = 0.005).
In Vivo Model	Endometrioma PDX model (PDX: END(K)265)

Experiment 1 Reporting the Activity Date of This ADC					[19]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.18-0.26 nM
Method Description	Two Trop-2 positive (CVX-8, ADX-3), and one Trop-2 negative (ADX-2) cell lines were used. A cell line with a strong Trop-2 expression (CVX-8) was used to test in vivo antitumor activity in xenografts models,in vitro experiments.
In Vitro Model	Primary cervical cancer	Primary cervical cancer cells		Homo sapiens
Experiment 2 Reporting the Activity Date of This ADC					[20]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	0.6 nM
Method Description	The inhibitory activity of sacituzumab govitecan govitecan against USC with heterogeneous Trop-2 expression was tested by admixing ARK2 USC cells (i.e., high Trop-2 expression) compared to control ADC (p< 0.05),in vitro.
In Vitro Model	Endometrial serous adenocarcinoma	USPC-ARK-2 cells		CVCL_IV73
Experiment 3 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.02 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Colon adenocarcinoma	COLO 205 cells		CVCL_0218
Experiment 4 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.44 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Pancreatic ductal adenocarcinoma	BxPC-3 cells		CVCL_0186
Experiment 5 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	1.86 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Prostate carcinoma	PC-3 cells		CVCL_0035
Experiment 6 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.5 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Pancreatic ductal adenocarcinoma	Capan-1 cells		CVCL_0237
Experiment 7 Reporting the Activity Date of This ADC					[22]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	3.9 nM
Method Description	The inhibitory activity of sacituzumab govitecan govitecan against USC with heterogeneous Trop-2 expression was tested by admixing ARK2 USC cells (i.e., high Trop-2 expression) compared to control ADC (p< 0.05),in vitro.
In Vitro Model	Endometrial serous adenocarcinoma	USPC-ARK-2 cells		CVCL_IV73
Experiment 8 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	7.19 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Lung adenocarcinoma	Calu-3 cells		CVCL_0609
Experiment 9 Reporting the Activity Date of This ADC					[21]
Efficacy Data	Half Maximal Inhibitory Concentration (IC50)	8.61 nM
Method Description	The hRS7 conjugates of the two SN-38 derivatives,using 0.4 mg or 0.2 mg/kg SN-38 twice weekly* 4 weeks,were equivalent in drug substitution (~6),cell binding (Kd =1.2 nmol/L), cytotoxicity (IC50=2.2 nmol/L), and serum stability in vitro (t/1/2= 20hours).
In Vitro Model	Lung squamous cell carcinoma	SK-MES-1 cells		CVCL_0630

Ref 1	Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics
Ref 2	Population Pharmacokinetics of Sacituzumab Govitecan in Patients with Metastatic Triple-Negative Breast Cancer and Other Solid Tumors
Ref 3	Abstract 3734: Pharmacokinetics of sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC) targeting Trop-2, in patients with diverse advanced solid tumors
Ref 4	Sacituzumab Govitecan: First Approval
Ref 5	Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers
Ref 6	Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial
Ref 7	Targeting Refractory Triple-Negative Breast Cancer with Sacituzumab Govitecan: A New Era in Precision Medicine
Ref 8	Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer. J Clin Oncol. 2022 Oct 10;40(29):3365-3376.
Ref 9	Analysis of patients without and with an initial triple-negative breast cancer diagnosis in the phase 3 randomized ASCENT study of sacituzumab govitecan in metastatic triple-negative breast cancer. Breast Cancer Res Treat. 2022 Sep;195(2):127-139.
Ref 10	Sacituzumab Govitecan in Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2021 Apr 22;384(16):1529-1541.
Ref 11	A Phase IIb, single arm, multicenter trial of sacituzumab govitecan in Chinese patients with metastatic triple-negative breast cancer who received at least two prior treatments. Int J Cancer. 2023 May 15;152(10):2134-2144. doi: 10.1002/ijc.34424. Epub 2023 Jan 30.
Ref 12	Therapy of Small Cell Lung Cancer (SCLC) with a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan. Clin Cancer Res. 2017 Oct 1;23(19):5711-5719.
Ref 13	Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial. Ann Oncol. 2021 Jun;32(6):746-756.
Ref 14	Therapy of Advanced Non-Small-Cell Lung Cancer With an SN-38-Anti-Trop-2 Drug Conjugate, Sacituzumab Govitecan. J Clin Oncol. 2017 Aug 20;35(24):2790-2797.
Ref 15	Efficacy and Safety of Anti-Trop-2 Antibody Drug Conjugate Sacituzumab Govitecan (IMMU-132) in Heavily Pretreated Patients With Metastatic Triple-Negative Breast Cancer. J Clin Oncol. 2017 Jul 1;35(19):2141-2148.
Ref 16	Sacituzumab Govitecan-hziy in Refractory Metastatic Triple-Negative Breast Cancer. N Engl J Med. 2019 Feb 21;380(8):741-751.
Ref 17	Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate for the treatment of diverse epithelial cancers: Safety and pharmacokinetics. Cancer. 2017 Oct 1;123(19):3843-3854.
Ref 18	Sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2, shows cytotoxic activity against poorly differentiated endometrial adenocarcinomas invitro and invivo. Mol Oncol. 2020 Mar;14(3):645-656.
Ref 19	Cervical carcinomas that overexpress human trophoblast cell-surface marker (Trop-2) are highly sensitive to the antibody-drug conjugate sacituzumab govitecan. Sci Rep. 2020 Jan 22;10(1):973.
Ref 20	Clinicopathological features of women with epithelial ovarian cancer and double heterozygosity for BRCA1 and BRCA2: A systematic review and case report analysis. Gynecol Oncol. 2020 Feb;156(2):377-386.
Ref 21	Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res. 2011 May 15;17(10):3157-69.
Ref 22	Invitro and invivo activity of sacituzumab govitecan, an antibody-drug conjugate targeting trophoblast cell-surface antigen 2 (Trop-2) in uterine serous carcinoma. Gynecol Oncol. 2020 Feb;156(2):430-438.