Study of Sacituzumab Govitecan-hziy (IMMU-132) in Adults With Epithelial Cancer

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01631552
• Collaborator: (none)
• Enrollment: 515
• Locations: 12
• Arms: 4
• Actual Duration (Months): 91.9
• Patients Per Site: 42.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The primary objective in Phase I is to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent administered in 21-day treatment cycles in previously treated participants with advanced epithelial cancer. In Phase II, the primary objective is to evaluate the safety and efficacy of sacituzumab govitecan-hziy administered in 21-day treatment cycles at a dose selected in Phase I.

Tumor types in the study will include: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma; Esophageal Cancer; Hepatocellular Carcinoma; Non-small Cell Lung Cancer; Small Cell Lung Cancer; Ovarian Epithelial Cancer; Carcinoma Breast Stage IV; Hormone-refractory Prostate Cancer; Head and Neck Cancers- Squamous Cell; Renal Cell Cancer; Urinary Bladder Neoplasms; Cervical Cancer; Endometrial Cancer; Glioblastoma Multiforme; Triple Negative Breast Cancer; Pancreatic Cancer	Drug: Sacituzumab Govitecan-hziy (SG)	Phase 1/Phase 2

Detailed Description

The outcome measures are planned to be assessed up to the data cutoff date. Following the data cutoff date, the participants will either stay on the study and will be followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data will be collected after the data cutoff date.

Study Design

• Study Type: Interventional
• Actual Enrollment: 515 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/II Study of IMMU-132 (hRS7-SN38 Antibody Drug Conjugate) in Patients With Epithelial Cancer
• Actual Study Start Date: Dec 17, 2012
• Actual Primary Completion Date: Mar 1, 2019
• Actual Study Completion Date: Aug 13, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Sacituzumab Govitecan-hziy (SG) 8 mg/kg Participants will receive sacituzumab govitecan-hziy (SG) 8 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy (SG); Administered via intravenous (IV) infusion; Other Names: hRS7-SN38 IMMU-132
Experimental: SG 10 mg/kg Participants will receive SG 10 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy (SG); Administered via intravenous (IV) infusion; Other Names: hRS7-SN38 IMMU-132
Experimental: SG 12 mg/kg Participants will receive SG 12 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy (SG); Administered via intravenous (IV) infusion; Other Names: hRS7-SN38 IMMU-132
Experimental: SG 18 mg/kg Participants will receive SG 18 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Drug: Sacituzumab Govitecan-hziy (SG); Administered via intravenous (IV) infusion; Other Names: hRS7-SN38 IMMU-132

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events [First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days]

   Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.03. An AE that met one or more of the following outcomes was classified as serious: Fatal Life-threatening Disabling/incapacitating Results in hospitalization or prolongs a hospital stay A congenital abnormality Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population.

2. Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death [First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)]

   Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).

3. Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events [First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)]

   Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).

4. Objective Response Rate (ORR) by Independent Central Review (ICR) [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.

5. Objective Response Rate by Local Assessment [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

Secondary Outcome Measures

1. Duration of Response by ICR [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.

2. Duration of Response by Local Assessment [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, duration of response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

3. Time to Response by ICR [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by ICR was assessed for the TNBC Target Population only.

4. Time to Response by Local Assessments [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

5. Clinical Benefit Rate (CBR) by Local Assessment [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Clinical benefit rate (CR+PR+[stable disease (SD) ≥ 6 months]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier. Per planned analysis, CBR by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

6. Progression Free Survival (PFS) by Local Assessment [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first. Per planned analysis, PFS by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

7. Overall Survival by Local Assessment [Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)]

   Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause. Per planned analysis, overall survival by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.

8. Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 [Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hours (± 30 minutes) for subsequent infusions]

   T1/2 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. T1/2 is defined as apparent terminal elimination half-life (h); calculated as 0.693/λz. The dose level evaluated for PK analysis was 10 mg/kg.

9. PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 [Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions]

   AUC0-24 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-24 is defined as area under the serum concentration-time curve from time 0 to 24 hours. The dose level evaluated for PK analysis was 10 mg/kg.

10. PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 [Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions]

    AUC0-168 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours. The dose level evaluated for PK analysis was 10 mg/kg.

11. PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 [Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions]

    AUC0-inf was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-inf is defined as area under the serum concentration-time curve from time 0 extrapolated to infinity. The dose level evaluated for PK analysis was 10 mg/kg.

12. PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38 [Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions]

    Cmax was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. The dose level evaluated for PK analysis was 10 mg/kg.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Individuals able to understand and give written informed consent.

• Histologically or cytologically confirmed epithelial cancer of one of the following types:

• Gastric adenocarcinoma (GC)

• Esophageal cancer (EC)

• Hepatocellular carcinoma (HCC)

• Non-small-cell lung cancer (NSCLC)

• Small-cell lung cancer (SCLC)

• Epithelial ovarian cancer (EOC)

• Cervical Cancer

• Endometrial Cancer

• Triple-negative breast cancer (TNBC)

• Non-triple-negative breast cancer

• Papillary thyroid cancer (excludes follicular, medullary, Hurthle cell, and anaplastic thyroid cancer)

• Glioblastoma multiforme (GBM)

• Hormone-refractory prostate cancer (HRPC)

• Head and neck cancers- squamous cell (SCCHN)

• Renal cell cancer (clear cell) (RCC)

• Urothelial cancer

• Stage IV (metastatic) disease (except for individuals with GBM).

• Refractory to or relapsed after at least one prior standard therapeutic regimen

• Adequate performance status (ECOG 0 or 1)

• Expected survival ≥ 6 months.

• Measurable disease by CT or MRI.

• At least 2 weeks beyond treatment (chemotherapy, investigational drugs including small molecular inhibitors, immunotherapy and/or radiation therapy) or major surgery and recovered from all acute toxicities to Grade 1 or less (except alopecia).

• At least 2 weeks beyond high dose systemic corticosteroids (however, low dose corticosteroids < 20 mg prednisone or equivalent daily are permitted).

• Adequate hematology without ongoing transfusional support (hemoglobin > 9 g/dL, absolute neutrophil count (ANC) > 1,500 per mm^{3, platelets > 100,000 per mm}3).

• Adequate renal and hepatic function (creatinine ≤ 2.0 x institutional upper limit of normal (IULN), bilirubin ≤ 1.5 IULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3.0 x IULN or 5 x IULN if know liver metastases).

• Otherwise, all toxicity at study entry ≤ Grade 1.

Exclusion Criteria:

• Women who are pregnant or lactating.

• Women of childbearing potential and fertile men unwilling to use effective contraception during study until conclusion of 12-week post-treatment evaluation period.

• Individuals with Gilbert's disease.

• Individuals with brain metastases can be enrolled only if treated, non-progressive brain metastases and off high-dose steroids (> 20 mg prednisone or equivalent) for at least 4 weeks.

• Presence of bulky disease (defined as any single mass > 7 cm in its greatest dimension). Individuals with a mass over 7 cm, but otherwise eligible, may be considered for enrollment after discussion and approval with the medical monitor.

• Individuals with active ≥ grade 2 anorexia, nausea or vomiting, and/or signs of intestinal obstruction.

• Individuals with non-melanoma skin cancer or carcinoma in situ of the cervix are eligible, while individuals with other prior malignancies must have had at least a 3-year disease-free interval.

• Individuals known to be HIV positive, hepatitis B positive, or hepatitis C positive.

• Known history of unstable angina, MI, or CHF present within 6 months or clinically significant cardiac arrhythmia (other than stable atrial fibrillation) requiring anti-arrhythmia therapy.

• Known history of clinically significant active COPD, or other moderate-to-severe chronic respiratory illness present within 6 months.

• Prior history of clinically significant bleeding, intestinal obstruction, or GI perforation within 6 months of initiation of study treatment.

• Infection requiring intravenous antibiotic use within 1 week.

• History of an anaphylactic reaction to irinotecan or ≥ Grade 3 GI toxicity to prior irinotecan,

• Other concurrent medical or psychiatric conditions that, in the Investigator's opinion, may be likely to confound study interpretation or prevent completion of study procedures and follow-up examinations.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Anschutz Medical Campus	Aurora	Colorado	United States	080045
2	Yale University School of Medicine	New Haven	Connecticut	United States	06511
3	Helen F. Graham Cancer Center	Newark	Delaware	United States	19713
4	MD Anderson Cancer Center Orlando (UF Health Cancer Center)	Orlando	Florida	United States	32806
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	IU Health Goshen Cancer Center	Goshen	Indiana	United States	46526
7	Massachusettes General Hospital	Boston	Massachusetts	United States	02114
8	Weill Cornell/New York Presbyterian Hospital	New York	New York	United States	10021
9	Columbia University Herbert Irving Cancer Center	New York	New York	United States	10032
10	Vanderbilt-Ingram Cancer Center	Nashville	Tennessee	United States	37212
11	Texas Oncology Sammons Cancer Center	Dallas	Texas	United States	75246
12	Virginia Mason Cancer Center	Seattle	Washington	United States	98111

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol - Jan 23, 2020
• Statistical Analysis Plan - Feb 27, 2019

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01631552
• Other Study ID Numbers: IMMU-132-01
• First Posted: Jun 29, 2012
• Last Update Posted: Aug 12, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Carcinoma; Lung Neoplasms; Glioblastoma; Small Cell Lung Carcinoma; Endometrial Neoplasms; Triple Negative Breast Neoplasms; Carcinoma, Ovarian Epithelial; Carcinoma, Renal Cell; Urinary Bladder Neoplasms; Breast Neoplasms

Study Results

Participant Flow

Recruitment Details

Participants were enrolled at study sites in the United States. The first participant was screened on 17 December 2012. The last study visit occurred on 13 August 2020. Outcome Measures were assessed up to the data cutoff date of 01 March 2019. Following the data cutoff date, the participants either stayed on the study and were followed for safety data collection or rolled into another Gilead-sponsored study. Therefore, only safety data was collected after the data cutoff date.

Pre-assignment Detail

Tumor types included in the study were as follows: cervical, colorectal, endometrial, ovarian, esophageal, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular, prostate, non-small-cell lung cancer, pancreatic, renal cell, small-cell lung cancer, non-triple negative breast cancer (non-TNBC), triple-negative breast cancer (TNBC) and metastatic urothelial cancer (mUC).

Arm/Group Title	Sacituzumab Govitecan-hziy (SG) 8 mg/kg	SG 10 mg/kg	SG 12 mg/kg	SG 18 mg/kg
Arm/Group Description	Participants received sacituzumab govitecan-hziy (SG) 8 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 10 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 12 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 18 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.
Period Title: Overall Study
STARTED	83	420	9	3
Enrolled and Treated	81	402	9	3
COMPLETED	81	400	9	3
NOT COMPLETED	2	20	0	0

Baseline Characteristics

Arm/Group Title	SG 8mg/kg	SG 10 mg/kg	SG 12 mg/kg	SG 18 mg/kg	Total
Arm/Group Description	Participants received sacituzumab govitecan-hziy 8 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 10 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 12 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Participants received sacituzumab govitecan-hziy 18 mg/kg of body weight via IV infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.	Total of all reporting groups
Overall Participants	81	402	9	3	495
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.1 (10.91)	59.8 (11.28)	59.1 (10.53)	56.0 (4.00)	60.0 (11.17)
Sex: Female, Male (Count of Participants)
Female	46 56.8%	281 69.9%	6 66.7%	1 33.3%	334 67.5%
Male	35 43.2%	121 30.1%	3 33.3%	2 66.7%	161 32.5%
Race/Ethnicity, Customized (Count of Participants)
White	67 82.7%	329 81.8%	6 66.7%	3 100%	405 81.8%
Black	6 7.4%	19 4.7%	2 22.2%	0 0%	27 5.5%
Asian	4 4.9%	13 3.2%	1 11.1%	0 0%	18 3.6%
Other	4 4.9%	41 10.2%	0 0%	0 0%	45 9.1%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	4 4.9%	16 4%	0 0%	0 0%	20 4%
Not Hispanic or Latino	77 95.1%	386 96%	9 100%	3 100%	475 96%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Experiencing Any Treatment Emergent Adverse Events and Serious Treatment Emergent Adverse Events
Description	Treatment-emergent adverse events (TEAEs) were defined as any adverse events (AEs) that begin or worsen on or after the start of study drug through 30 days after the last dose of study drug. The severity was graded based on the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 4.03. An AE that met one or more of the following outcomes was classified as serious: Fatal Life-threatening Disabling/incapacitating Results in hospitalization or prolongs a hospital stay A congenital abnormality Other important medical events may also be considered serious AEs if they may require medical or surgical intervention to prevent one of the outcomes listed above Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population.
Time Frame	First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months) plus 30 days

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG OSP: All participants who received at least 1 dose of SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population	Overall Safety Population (OSP)
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as Hormone receptor-positive/Human epidermal growth factor receptor 2-negative (HR+/HER2-), had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.	Overall 495 participants were enrolled in the study and received at least one dose of 10 mg/kg, 8 mg/kg, 12mg/kg, or 18mg/kg SG. These participants were included in the Overall Safety Population and analyzed for safety.
Measure Participants	108	54	45	495
Adverse Events	100.0 123.5%	100.0 24.9%	100.0 1111.1%	99.8 3326.7%
Serious Adverse Events	30.6 37.8%	35.2 8.8%	42.2 468.9%	38.8 1293.3%

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Sacituzumab Govitecan-hziy (SG) Due to Any Adverse Events, Excluding Adverse Events Leading to Death
Description	Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
Time Frame	First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG OSP: All participants who received at least 1 dose of SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population	Overall Safety Population (OSP)
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.	Overall 495 participants were enrolled in the study and received at least one dose of 10 mg/kg, 8 mg/kg, 12mg/kg, or 18mg/kg SG. These participants were included in the Overall Safety Population and analyzed for safety.
Measure Participants	108	54	45	495
Number [Percentage of participants]	2.8 3.5%	5.6 1.4%	15.6 173.3%	8.1 270%

3. Primary Outcome

Title	Percentage of Participants Who Required Dose Interruption Due to Any Adverse Events
Description	Per planned analysis, populations to be used for evaluation of this outcome measure were as follows: Triple Negative Breast Cancer (TNBC) Target Population, HR+/HER2- Metastatic Breast Cancer (mBC) Population, Metastatic Urothelial Cancer (mUC) Population, and Overall Safety Population (OSP).
Time Frame	First dose date up to last dose for data cutoff date of 01 March 2019 (maximum duration: 55.2 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG OSP: All participants who received at least 1 dose of SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population	Overall Safety Population (OSP)
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.	Overall 495 participants were enrolled in the study and received at least one dose of 10 mg/kg, 8 mg/kg, 12mg/kg, or 18mg/kg SG. These participants were included in the Overall Safety Population and analyzed for safety.
Measure Participants	108	54	45	495
Number [Percentage of participants]	45.4 56%	46.3 11.5%	51.1 567.8%	51.7 1723.3%

4. Primary Outcome

Title	Objective Response Rate (ORR) by Independent Central Review (ICR)
Description	ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by ICR assessment according to RECIST1.1. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥ 30% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease and who received SG at a dose of 10 mg/kg.

Arm/Group Title	TNBC Target Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.
Measure Participants	108
Number (95% Confidence Interval) [Percentage of participants]	34.3 42.3%

5. Primary Outcome

Title	Objective Response Rate by Local Assessment
Description	ORR was defined as the rate an overall best response of either complete response (CR) or partial response (PR) by local assessment. CR was defined as the disappearance of all target lesions and reduction in short axis of any pathologic lymphnode to <10 mm. PR was defined as ≥3 0% decrease in the sum of diameters of target lesions, taking the baseline sum diameters. Per planned analysis, ORR by Local Assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Number (95% Confidence Interval) [Percentage of participants]	33.3 41.1%	31.5 7.8%	28.9 321.1%

6. Secondary Outcome

Title	Duration of Response by ICR
Description	Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease and who received SG at a dose of 10 mg/kg. Per planned analysis, ORR by ICR was assessed for the TNBC Target Population only.

Arm/Group Title	TNBC Target Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.
Measure Participants	108
Median (95% Confidence Interval) [months]	9.1

7. Secondary Outcome

Title	Duration of Response by Local Assessment
Description	Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started). Per planned analysis, duration of response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Median (95% Confidence Interval) [months]	7.7	8.7	12.9

8. Secondary Outcome

Title	Time to Response by ICR
Description	Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by ICR was assessed for the TNBC Target Population only.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.
Measure Participants	108
Median (Full Range) [months]	2.2

9. Secondary Outcome

Title	Time to Response by Local Assessments
Description	Time to response was defined as the time from the first dose to the first documentation of response (PR or CR). Per planned analysis, time to response by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population (TNBC Population)	HR+/HER2- mBC Population (Non-TNBC)	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Median (Full Range) [months]	2.0	2.1	1.9

10. Secondary Outcome

Title	Clinical Benefit Rate (CBR) by Local Assessment
Description	Clinical benefit rate (CR+PR+[stable disease (SD) ≥ 6 months]) is defined as those participants with best response as CR or PR or else SD with a duration of at least 6 months. SD for 6 months duration was defined as the time from the first dose to the first documentation of PD or to the last adequate response assessment prior to data cut-off date, whichever is earlier. Per planned analysis, CBR by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Number (95% Confidence Interval) [Percentage of participants]	45.4 56%	44.4 11%	44.4 493.3%

11. Secondary Outcome

Title	Progression Free Survival (PFS) by Local Assessment
Description	Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first. Per planned analysis, PFS by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Median (95% Confidence Interval) [months]	5.6	5.5	6.8

12. Secondary Outcome

Title	Overall Survival by Local Assessment
Description	Overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause. Per planned analysis, overall survival by local assessment was assessed for TNBC Target Population, HR+/HER2-mBC Population, and mUC Population.
Time Frame	Up to data cutoff date of 01 March 2019 (maximum duration: 74 months)

Outcome Measure Data

Analysis Population Description

Target mTNBC: Participants with mTNBC who received at least 2 prior therapies for metastatic disease & who received at least 1 dose of 10 mg/kg SG HR+/HER2-mBC: Participants with HR+/HER2- mBC who progressed on at least 1 prior hormonal therapy & who received at least 1 dose of 10 mg/kg SG mUC: Participants who had relapsed after or were refractory to at least 1 prior treatments & who received at least 1 dose of 10 mg/kg SG

Arm/Group Title	TNBC Target Population	HR+/HER2- mBC Population	mUC Population
Arm/Group Description	Overall 144 participants with TNBC were enrolled in the study and received at least one dose of SG. Of these 144 participants, 108 received at least 2 prior therapies for metastatic disease and were treated with SG at a starting dose of 10mg/kg. These 108 participants were included in the analysis of safety and were referred to as the TNBC Target Population.	Overall, 68 participants with non-TNBC were enrolled in the study and received at least one dose of SG. Of these 68 participants, 54 were confirmed as HR+/HER2-, had progressed on at least one prior hormonal therapy in the metastatic setting, and had received at least one dose of 10 mg/kg SG. These 54 participants were included in the analysis of safety and were referred to as the HR+/HER2- mBC Population.	Overall 49 participants with metastatic urothelial cancer were enrolled in the study and received at least one dose of SG. Of these 49 participants, 45 had either relapsed after or were refractory to at least one prior standard therapeutic regimen and received at least one dose of 10 mg/kg SG. These 45 participants were included in the analysis of safety and were referred to as the mUC Population.
Measure Participants	108	54	45
Median (95% Confidence Interval) [months]	13.0	12.0	16.8

13. Secondary Outcome

Title	Pharmacokinetic (PK) Parameter: T1/2 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Description	T1/2 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. T1/2 is defined as apparent terminal elimination half-life (h); calculated as 0.693/λz. The dose level evaluated for PK analysis was 10 mg/kg.
Time Frame	Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hours (± 30 minutes) for subsequent infusions

Outcome Measure Data

Analysis Population Description

Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head & neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.

Arm/Group Title	SG 10 mg/kg
Arm/Group Description	Participants included adults with the following tumor types: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non-triple-negative breast cancer, triple-negative breast cancer, and metastatic urothelial cancer. All participants received SG 10 mg/kg of body weight by IV infusion on Days 1 and 8 of a 21-day treatment cycle.
Measure Participants	128
Total Antibody	66.6 (14.4)
SN-38G	21.4 (24.5)
Total SN-38	20.2 (26.6)
Sacituzumab Govitecan-hziy (SG)	15.0 (15.3)
Free SN-38	17.1 (18.6)

14. Secondary Outcome

Title	PK Parameter: AUC0-24 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Description	AUC0-24 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-24 is defined as area under the serum concentration-time curve from time 0 to 24 hours. The dose level evaluated for PK analysis was 10 mg/kg.
Time Frame	Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions

Outcome Measure Data

Analysis Population Description

Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head & neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.

Arm/Group Title	SG 10 mg/kg
Arm/Group Description	Participants included adults with the following tumor types: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non-triple-negative breast cancer, triple-negative breast cancer, and metastatic urothelial cancer. All participants received SG 10 mg/kg of body weight by IV infusion on Days 1 and 8 of a 21-day treatment cycle.
Measure Participants	128
Total Antibody	4940 (30.1)
SN-38G	0.370 (45.6)
Total SN-38	65.5 (29.2)
Sacituzumab Govitecan-hziy (SG)	3290 (25.2)
Free SN-38	1.67 (58.5)

15. Secondary Outcome

Title	PK Parameter: AUC0-168 of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Description	AUC0-168 was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-168 is defined as area under the serum concentration-time curve from time 0 to 168 hours. The dose level evaluated for PK analysis was 10 mg/kg.
Time Frame	Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions

Outcome Measure Data

Analysis Population Description

Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head & neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.

Arm/Group Title	SG 10 mg/kg
Arm/Group Description	Participants included adults with the following tumor types: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non-triple-negative breast cancer, triple-negative breast cancer, and metastatic urothelial cancer. All participants received SG 10 mg/kg of body weight by IV infusion on Days 1 and 8 of a 21-day treatment cycle.
Measure Participants	128
Total Antibody	20800 (22.2)
SN-38G	0.842 (50.0)
Total SN-38	107 (25.4)
Sacituzumab Govitecan-hziy (SG)	5050 (24.4)
Free SN-38	3.08 (56.6)

16. Secondary Outcome

Title	PK Parameter: AUC0-inf of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Description	AUC0-inf was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. AUC0-inf is defined as area under the serum concentration-time curve from time 0 extrapolated to infinity. The dose level evaluated for PK analysis was 10 mg/kg.
Time Frame	Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions

Outcome Measure Data

Analysis Population Description

Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head & neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.

Arm/Group Title	SG 10 mg/kg
Arm/Group Description	Participants included adults with the following tumor types: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non-triple-negative breast cancer, triple-negative breast cancer, and metastatic urothelial cancer. All participants received SG 10 mg/kg of body weight by IV infusion on Days 1 and 8 of a 21-day treatment cycle.
Measure Participants	128
Total Antibody	25100 (20.5)
SN-38G	0.850 (50.7)
Total SN-38	107 (25.5)
Sacituzumab Govitecan-hziy (SG)	5050 (24.4)
Free SN-38	3.08 (56.6)

17. Secondary Outcome

Title	PK Parameter: Cmax of Total Antibody, SN-38 Glucuronide, Total SN-38, Sacituzumab Govitecan-hziy, and Free SN-38
Description	Cmax was determined for 5 analytes: total antibody, SN-38 glucuronide, total SN-38, free SN-38, and sacituzumab govitecan-hziy, a derived antibody drug conjugate (ADC) concentration. SN-38 is one of the components of sacituzumab govitecan-hziy. Cmax is defined as maximum observed serum concentration obtained directly from the observed concentration-time data. The dose level evaluated for PK analysis was 10 mg/kg.
Time Frame	Cycle 1: Preinfusion, 30 minutes and 3-4 hours post infusion, then 1 day, 2 days, 3 days, and 7 days later (1 Cycle = 21 days). Infusion duration: 3 hours (± 30 minutes) for 1st infusion; 1-2 hour (± 30 minutes) for subsequent infusions

Outcome Measure Data

Analysis Population Description

Participants with epithelial cancer that involved any one of the following with available data were analyzed: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head & neck cancers- squamouse cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non TNBC, TNBC and mUC.

Arm/Group Title	SG 10 mg/kg
Arm/Group Description	Participants included adults with the following tumor types: cervical cancer, colorectal cancer, endometrial cancer, epithelial ovarian cancer, esophageal cancer, gastric adenocarcinoma, glioblastoma multiforme, head and neck cancers- squamous cell, hepatocellular carcinoma, hormone-refractory prostate cancer, metastatic, non-small-cell lung cancer, pancreatic ductal adenocarcinoma, renal cell cancer, small-cell lung cancer, non-triple-negative breast cancer, triple-negative breast cancer, and metastatic urothelial cancer. All participants received SG 10 mg/kg of body weight by IV infusion on Days 1 and 8 of a 21-day treatment cycle.
Measure Participants	128
Total Antibody	245 (26.9)
SN-38G	0.0206 (50.4)
Total SN-38	4.39 (25.2)
Sacituzumab Govitecan-hziy (SG)	220 (24.7)
Free SN-38	0.0992 (61.1)

Adverse Events

Time Frame	- Adverse Events: First dose date up to 91.88 months plus 30 days - All-Cause Mortality: First dose date up to 91.88 months
Adverse Event Reporting Description	Overall Safety Population: All participants who received at least 1 dose of SG. Per planned analysis, data were collected for the Overall Safety Population, pooling all participants regardless of dose level received.
Arm/Group Title	Overall Safety Population
Arm/Group Description	All participants who were enrolled in the study and received one dose of sacituzumab govitecan-hziy (SG) at dose level of either 8 mg/kg, 10 mg/kg, 12 mg/kg, or 18 mg/kg of body weight via intravenous (IV) infusion on Days 1 and 8 of a 21-day treatment cycle until disease progression or unacceptable toxicity.
All Cause Mortality
	Overall Safety Population
	Affected / at Risk (%)	# Events
Total	422/495 (85.3%)
Serious Adverse Events
	Overall Safety Population
	Affected / at Risk (%)	# Events
Total	192/495 (38.8%)
Blood and lymphatic system disorders
Anaemia	4/495 (0.8%)
Febrile neutropenia	20/495 (4%)
Leukocytosis	1/495 (0.2%)
Leukopenia	1/495 (0.2%)
Lymphopenia	1/495 (0.2%)
Neutropenia	7/495 (1.4%)
Cardiac disorders
Acute myocardial infarction	1/495 (0.2%)
Atrial fibrillation	3/495 (0.6%)
Cardiac tamponade	1/495 (0.2%)
Cardio-respiratory arrest	1/495 (0.2%)
Myocardial infarction	2/495 (0.4%)
Endocrine disorders
Inappropriate antidiuretic hormone secretion	1/495 (0.2%)
Eye disorders
Purtscher retinopathy	1/495 (0.2%)
Gastrointestinal disorders
Abdominal pain	6/495 (1.2%)
Abdominal pain upper	1/495 (0.2%)
Colitis	3/495 (0.6%)
Constipation	1/495 (0.2%)
Diarrhoea	18/495 (3.6%)
Dysphagia	2/495 (0.4%)
Gastrointestinal haemorrhage	1/495 (0.2%)
Intestinal obstruction	2/495 (0.4%)
Lower gastrointestinal haemorrhage	1/495 (0.2%)
Nausea	10/495 (2%)
Neutropenic colitis	2/495 (0.4%)
Oesophageal obstruction	1/495 (0.2%)
Oesophagitis	1/495 (0.2%)
Pouchitis	1/495 (0.2%)
Proctalgia	1/495 (0.2%)
Small intestinal obstruction	7/495 (1.4%)
Upper gastrointestinal haemorrhage	1/495 (0.2%)
Vomiting	11/495 (2.2%)
General disorders
Asthenia	3/495 (0.6%)
Chest pain	4/495 (0.8%)
Face oedema	1/495 (0.2%)
Fatigue	4/495 (0.8%)
Gait disturbance	1/495 (0.2%)
Generalised oedema	2/495 (0.4%)
Localised oedema	2/495 (0.4%)
Non-cardiac chest pain	1/495 (0.2%)
Oedema peripheral	2/495 (0.4%)
Pain	5/495 (1%)
Pyrexia	4/495 (0.8%)
Systemic inflammatory response syndrome	1/495 (0.2%)
Hepatobiliary disorders
Bile duct stenosis	1/495 (0.2%)
Bile duct stone	1/495 (0.2%)
Cholecystitis	1/495 (0.2%)
Hyperbilirubinaemia	2/495 (0.4%)
Immune system disorders
Anaphylactic reaction	1/495 (0.2%)
Infections and infestations
Clostridium difficile colitis	2/495 (0.4%)
Clostridium difficile infection	1/495 (0.2%)
Covid-19 pneumonia	1/495 (0.2%)
Diverticulitis	1/495 (0.2%)
Enterocolitis infectious	1/495 (0.2%)
Epiglottitis	1/495 (0.2%)
Escherichia infection	1/495 (0.2%)
Escherichia urinary tract infection	1/495 (0.2%)
Herpes zoster	1/495 (0.2%)
Influenza	1/495 (0.2%)
Liver abscess	1/495 (0.2%)
Peritonitis	1/495 (0.2%)
Pleural infection	1/495 (0.2%)
Pneumonia	14/495 (2.8%)
Pyelonephritis	1/495 (0.2%)
Rectal abscess	1/495 (0.2%)
Respiratory syncytial virus infection	1/495 (0.2%)
Sepsis	3/495 (0.6%)
Septic shock	1/495 (0.2%)
Staphylococcal bacteraemia	1/495 (0.2%)
Upper respiratory tract infection	1/495 (0.2%)
Urinary tract infection	3/495 (0.6%)
Vascular device infection	1/495 (0.2%)
Injury, poisoning and procedural complications
Fall	1/495 (0.2%)
Femur fracture	1/495 (0.2%)
Humerus fracture	1/495 (0.2%)
Lower limb fracture	1/495 (0.2%)
Post procedural fever	1/495 (0.2%)
Post procedural haemorrhage	1/495 (0.2%)
Radiation pneumonitis	1/495 (0.2%)
Spinal compression fracture	1/495 (0.2%)
Investigations
Neutrophil count decreased	3/495 (0.6%)
Metabolism and nutrition disorders
Dehydration	4/495 (0.8%)
Failure to thrive	2/495 (0.4%)
Hypernatraemia	1/495 (0.2%)
Hypokalaemia	1/495 (0.2%)
Hyponatraemia	1/495 (0.2%)
Malnutrition	1/495 (0.2%)
Musculoskeletal and connective tissue disorders
Arthralgia	1/495 (0.2%)
Back pain	2/495 (0.4%)
Muscular weakness	2/495 (0.4%)
Musculoskeletal pain	1/495 (0.2%)
Pain in extremity	1/495 (0.2%)
Pathological fracture	1/495 (0.2%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma	1/495 (0.2%)
Metastases to central nervous system	1/495 (0.2%)
Metastases to spine	1/495 (0.2%)
Squamous cell carcinoma of skin	1/495 (0.2%)
Nervous system disorders
Cerebrovascular accident	1/495 (0.2%)
Dizziness	1/495 (0.2%)
Hypoaesthesia	1/495 (0.2%)
Spinal cord compression	1/495 (0.2%)
Syncope	3/495 (0.6%)
Vocal cord paralysis	1/495 (0.2%)
Psychiatric disorders
Confusional state	2/495 (0.4%)
Delirium	1/495 (0.2%)
Depression	1/495 (0.2%)
Mental status changes	4/495 (0.8%)
Renal and urinary disorders
Acute kidney injury	2/495 (0.4%)
Renal failure	1/495 (0.2%)
Urinary retention	2/495 (0.4%)
Urinary tract obstruction	1/495 (0.2%)
Reproductive system and breast disorders
Vaginal haemorrhage	1/495 (0.2%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure	1/495 (0.2%)
Aspiration	1/495 (0.2%)
Bronchial obstruction	1/495 (0.2%)
Chronic obstructive pulmonary disease	1/495 (0.2%)
Dyspnoea	12/495 (2.4%)
Dyspnoea exertional	1/495 (0.2%)
Epistaxis	1/495 (0.2%)
Haemoptysis	1/495 (0.2%)
Hiccups	1/495 (0.2%)
Hypoxia	3/495 (0.6%)
Pleural effusion	7/495 (1.4%)
Pneumonia aspiration	1/495 (0.2%)
Pulmonary embolism	4/495 (0.8%)
Respiratory distress	1/495 (0.2%)
Respiratory failure	4/495 (0.8%)
Vocal cord dysfunction	1/495 (0.2%)
Skin and subcutaneous tissue disorders
Paraneoplastic dermatomyositis	1/495 (0.2%)
Vascular disorders
Deep vein thrombosis	2/495 (0.4%)
Embolism	2/495 (0.4%)
Hypertension	2/495 (0.4%)
Hypotension	1/495 (0.2%)
Peripheral embolism	1/495 (0.2%)
Other (Not Including Serious) Adverse Events
	Overall Safety Population
	Affected / at Risk (%)	# Events
Total	490/495 (99%)
Blood and lymphatic system disorders
Anaemia	207/495 (41.8%)
Neutropenia	196/495 (39.6%)
Gastrointestinal disorders
Abdominal distension	25/495 (5.1%)
Abdominal pain	108/495 (21.8%)
Constipation	184/495 (37.2%)
Diarrhoea	303/495 (61.2%)
Dyspepsia	26/495 (5.3%)
Gastrooesophageal reflux disease	25/495 (5.1%)
Nausea	342/495 (69.1%)
Stomatitis	27/495 (5.5%)
Vomiting	220/495 (44.4%)
General disorders
Asthenia	27/495 (5.5%)
Chest pain	33/495 (6.7%)
Chills	33/495 (6.7%)
Fatigue	280/495 (56.6%)
Oedema peripheral	79/495 (16%)
Pain	27/495 (5.5%)
Pyrexia	80/495 (16.2%)
Infections and infestations
Upper respiratory tract infection	60/495 (12.1%)
Urinary tract infection	65/495 (13.1%)
Investigations
Activated partial thromboplastin time prolonged	33/495 (6.7%)
Alanine aminotransferase increased	44/495 (8.9%)
Aspartate aminotransferase increased	47/495 (9.5%)
Blood alkaline phosphatase increased	55/495 (11.1%)
Lymphocyte count decreased	38/495 (7.7%)
Neutrophil count decreased	98/495 (19.8%)
Weight decreased	75/495 (15.2%)
White blood cell count decreased	77/495 (15.6%)
Metabolism and nutrition disorders
Decreased appetite	171/495 (34.5%)
Dehydration	78/495 (15.8%)
Hyperglycaemia	54/495 (10.9%)
Hypoalbuminaemia	30/495 (6.1%)
Hypocalcaemia	26/495 (5.3%)
Hypokalaemia	89/495 (18%)
Hypomagnesaemia	89/495 (18%)
Hyponatraemia	38/495 (7.7%)
Hypophosphataemia	65/495 (13.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	68/495 (13.7%)
Back pain	75/495 (15.2%)
Muscular weakness	31/495 (6.3%)
Myalgia	28/495 (5.7%)
Pain in extremity	45/495 (9.1%)
Nervous system disorders
Dizziness	81/495 (16.4%)
Dysgeusia	33/495 (6.7%)
Headache	78/495 (15.8%)
Neuropathy peripheral	30/495 (6.1%)
Psychiatric disorders
Anxiety	30/495 (6.1%)
Depression	29/495 (5.9%)
Insomnia	57/495 (11.5%)
Renal and urinary disorders
Haematuria	25/495 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	101/495 (20.4%)
Dyspnoea	100/495 (20.2%)
Epistaxis	32/495 (6.5%)
Nasal congestion	29/495 (5.9%)
Rhinorrhoea	40/495 (8.1%)
Skin and subcutaneous tissue disorders
Alopecia	216/495 (43.6%)
Dry skin	38/495 (7.7%)
Pruritus	62/495 (12.5%)
Rash	78/495 (15.8%)
Vascular disorders
Hypotension	27/495 (5.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Immunomedics, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Immunomedics in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years