Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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The primary objectives of this study are as follows: Phase 1 (sequential dose-escalation): to evaluate the safety and tolerability of sacituzumab govitecan-hziy (SG) as a single agent and to determine the recommended Phase 2 dose (RP2D) of SG in Japanese participants with advance solid tumors. Phase 2: Evaluate the safety and efficacy of SG in Japanese participants with metastatic triple-negative breast cancer (mTNBC), hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC), and metastatic urothelial cancer (mUC).

Official Title
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A Phase 1/2 Open-Label Study of Sacituzumab Govitecan in Japanese Patients With Advanced Solid Tumors (ASCENT-J02)

Conditions
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Advanced Solid Tumor, Metastatic Triple-Negative Breast Cancer, HR+/HER2- Metastatic Breast Cancer, Metastatic Urothelial Cancer

Intervention / Treatment
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* Drug: Sacituzumab Govitecan-hziy


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal (ULN)), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN Creatinine clearance ≥ 30 mL/min Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception. Phase 1 only: Histologically or cytologically confirmed advanced solid tumor that is refractory to or intolerant of all standard therapy or for which no standard therapy is available. Phase 2 metastatic triple-negative breast cancer (mTNBC) Cohort: Histologically or cytologically confirmed TNBC per American Society of Clinical Oncologists/College of American Pathologists (ASCO/CAP) criteria, based on the most recent analyzed biopsy or other pathology specimen. Refractory to or relapsed after at least 2 prior standard-of-care chemotherapy regimens for unresectable, locally advanced or metastatic breast cancer. Phase 2 hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer (HR+/HER2- mBC) Cohort: Documented evidence of HR+/HER2- mBC confirmed by a local laboratory and defined per ASCO/CAP criteria. Refractory to or relapsed after 2 prior systemic chemotherapy regimens for metastatic disease. Phase 2 metastatic urothelial cancer (mUC) Cohort: Histologically documented UC that is metastatic or locally advanced unresectable. Progressed or recurred following receipt of platinum-containing regimen and anti-PD-1/PD-L1 therapy for metastatic or locally advanced unresectable disease Key Exclusion Criteria: Positive serum pregnancy test, or females who may possibly be pregnant Known Gilbert's disease Have previously received antibody drug conjugate containing topoisomerase I inhibitors Presence of bulky disease (defined as any single mass > 7 cm in greatest dimension). Known to be HIV positive, or hepatitis B virus (HBV) surface antigen positive or hepatitis C virus (HCV) antibody positive at screening Known history of significant cardiac disease Known history of clinically significant active chronic obstructive pulmonary disease, or other moderate-to-severe chronic respiratory illness History of interstitial lung disease History of clinically significant gastrointestinal (GI) bleeding, have active chronic inflammatory bowel disease (ulcerative colitis, Crohn's disease) or GI perforation Individuals with a history of anaphylactic reaction to irinotecan. Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors<br>(Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive sacituzumab govitecan-hziy (SG) 6 mg/kg by intravenous (IV) injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors<br>(Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 8 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors<br>(Phase 1 Cohort A: dose escalation) Japanese participants with advanced solid tumors will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism<br>(Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 6 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy 8 mg, UGT1A1 Polymorphism<br>(Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 8 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism<br>(Phase 1 Cohort B: dose escalation) Japanese participants with UGT1A1 polymorphism will receive SG 10 mg/kg by IV injection on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC)<br>(Phase 2: dose expansion) Japanese participants with mTNBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21-day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC)<br>(Phase 2) Japanese participants with HR+/HER2- mBC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|
| Experimental: Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC)<br>(Phase 2) Japanese participants with mUC will receive SG at the recommended Phase 2 dose (RP2D) on Day 1 and Day 8 of a 21 day cycle until disease progression or unacceptable toxicity. | Drug: Sacituzumab Govitecan-hziy<br>* Administered intravenously (IV)<br>* Other names: GS-0132;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 |  | First dose date to last dose date (Up to 15 weeks) plus 30 days | 
| Phase 1: Percentage of Participants Experiencing laboratory abnormalities Defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 4.03 |  | First dose date to last dose date (Up to 15 weeks) plus 30 days | 
| Phase 1: Percentage of Participants Experiencing Dose-limiting toxicity (DLTs) per Dose level |  | First dose date up to 21 days | 
| Phase 2: Objective Response Rate (ORR) Assessed by Independent Review Committee (IRC) | ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) confirmed at least 4 weeks later as assessed by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) | Up to 17 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1:Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38 | Cmax is defined as the maximum observed concentration of drug | Up to 33 months | 
| Phase 1:PK parameters Tmax of SG and Free SN-38 | Tmax is defined as time (observed time point) of Cmax | Up to 33 months | 
| Phase 1:PK parameters AUC0-168h of SG and Free SN-38 | AUC0-168h is defined as partial area under the concentration of drug over time between 0 to time 168-hour. | Up to 33 months | 
| Phase 1: Percentage of Participants Who Developed Anti-Drug Antibodies (ADAs) Against SG |  | Up to 33 months | 
| Phase 2: Percentage of Participants Experiencing TEAEs Defined by NCI CTCAE Version 4.03 |  | First dose date to last dose date (Up to 33 months) plus 30 days | 
| Phase 2: Percentage of Participants Experiencing Laboratory Abnormalities Defined by NCI CTCAE Version 4.03 |  | First dose date to last dose date (Up to 33 months) plus 30 days | 
| Phase 2: Progression-free survival (PFS) Assessed by Investigator | PFS is defined as the interval from the first dose of SG to the earlier of the first documentation of objective progressive disease (PD) or death from any cause, whichever comes first. | Up to 33 months | 
| Phase 2: ORR Assessed by Investigator | ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1. | Up to 17 months | 
| Phase 2: Overall Survival (OS) | OS is defined as the time from date of first dose of SG to death from any cause, whichever comes first. | Up to 33 months | 
| Phase 2: Duration of Response (DOR) Assessed by Investigator | DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause. | Up to 33 months | 
| Phase 2: Time to response (TTR) Assessed by Investigator | TTR is defined as the time from first dose of SG to the first documentation of CR or PR. | Up to 17 months | 
| Phase 2: Progression-free survival (PFS) Assessed by IRC | PFS is defined as the interval from the first dose of SG to the earlier of the first documentation of objective progressive disease (PD) or death from any cause, whichever comes first. | Up to 33 months | 
| Phase 2: Duration of Response (DOR) Assessed by IRC | DOR is defined as the time from the first documentation of CR or PR to the earlier of the first documentation of objective PD or death from any cause. | Up to 33 months | 
| Phase 2: Time to response (TTR) Assessed by IRC | TTR is defined as the time from first dose of SG to the first documentation of CR or PR. | Up to 17 months |