Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors (ASCENT-J02)

Gilead Sciences

Status and phase: Active, not recruiting; Phase 2; Phase 1

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

Treatments: Drug: Sacituzumab Govitecan-hziy

Study type: Interventional

Funder types: Industry

Identifiers

NCT05101096

jRCT2031210346 (Registry Identifier)

GS-US-569-6172

Details and patient eligibility

About

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).

Enrollment: 135 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 locally advanced unresectable or 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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135 participants in 8 patient groups

Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC)

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC)

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy

Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC)

Experimental group

Description:

(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.

Treatment:

Drug: Sacituzumab Govitecan-hziy