Study of Sacituzumab Govitecan (SG) in Japanese Participants With Advanced Solid Tumors
- Conditions
- HR+/HER2- Metastatic Breast CancerMetastatic Urothelial CancerAdvanced Solid TumorMetastatic Triple-Negative Breast Cancer
- Interventions
- Registration Number
- NCT05101096
- Lead Sponsor
- Gilead Sciences
- Brief Summary
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).
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 143
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Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1
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Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) as per RECIST Version 1.1 criteria
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Adequate hematologic counts without transfusional or growth factor support within 2 weeks of study drug initiation
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Adequate hepatic function (bilirubin ≤ 1.5 upper limit of normal (ULN)), alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 ULN
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Creatinine clearance ≥ 30 mL/min
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Male and female individuals of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception.
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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.
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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.
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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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC) Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC) Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism Sacituzumab Govitecan-hziy (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. Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC) Sacituzumab Govitecan-hziy (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.
- Primary Outcome Measures
Name Time Method 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:(Metastatic Triple-negative Breast Cancer (mTNBC);Hormone Receptor-positive/Human Epidermal Growth Factor Receptor 2-negative Metastatic Breast Cancer (HR+/HER2- mBC) Cohorts):Objective Response Rate (ORR) as Assessed by IRC Up to 17 months 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) as assessed by Independent Review Committee (IRC).
Phase 2 (Metastatic Urothelial Cancer (mUC) Cohort): ORR as Assessed by Investigator Up to 17 months 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)
- Secondary Outcome Measures
Name Time Method Phase 1: Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38 Up to 33 months Cmax is defined as the maximum observed concentration of drug
Phase 1: PK Parameter: Tmax of SG and Free SN-38 Up to 33 months Tmax is defined as time (observed time point) of Cmax
Phase 1: PK Parameter: AUC0-168h of SG and Free SN-38 Up to 33 months AUC0-168h is defined as partial area under the concentration of drug over time between 0 to time 168-hour.
Phase 1 : Percentage of Participants Who Develop Anti-Drug Antibodies (ADAs) Against SG Up to 33 months Phase 2 (All Cohorts): 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 (All Cohorts): 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(All Cohorts): Progression-free survival (PFS) as Assessed by Investigator Up to 33 months 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.
Phase 2 (All Cohorts): ORR as Assessed by Investigator Up to 17 months ORR is defined as the proportion of participants who achieve a CR or PR as assessed by RECIST v1.1.
Phase 2 (All Cohorts): Overall Survival (OS) Up to 33 months OS is defined as the time from date of first dose of SG to death from any cause, whichever comes first.
Phase 2 (All Cohorts): Duration of Response (DOR) as Assessed by Investigator Up to 33 months 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.
Phase 2 (All Cohorts): Time to response (TTR) as Assessed by Investigator Up to 17 months TTR is defined as the time from first dose of SG to the first documentation of CR or PR.
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Progression-free survival (PFS) as Assessed by IRC Up to 33 months 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.
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Duration of Response (DOR) as Assessed by IRC Up to 33 months 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.
Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Time to response (TTR) as Assessed by IRC Up to 17 months TTR is defined as the time from first dose of SG to the first documentation of CR or PR.
Trial Locations
- Locations (34)
Kagawa University Hospital
🇯🇵Kagawa, Japan
Aichi Cancer Center Hospital
🇯🇵Aichi, Japan
Akita University Hospital
🇯🇵Akita, Japan
Tohoku University Hospital
🇯🇵Aoba-ku, Japan
Hirosaki University Hospital
🇯🇵Aomori, Japan
Kanagawa Cancer Center
🇯🇵Asahi-ku, Japan
Juntendo University Hospital
🇯🇵Bunkyo-ku, Japan
Chiba Cancer Center
🇯🇵Chiba, Japan
National Cancer Center Hospital East
🇯🇵Chiba, Japan
Chiba Cancer
🇯🇵Chuo-ku, Japan
Nagoya University Hospital
🇯🇵Chuo-ku, Japan
Osaka International Cancer Institute
🇯🇵Osaka, Japan
Shikoku Cancer Center
🇯🇵Ehime, Japan
National Hospital Organization Shikoku Cancer Center
🇯🇵Ehime, Japan
Hyogo Cancer Center
🇯🇵Hyogo, Japan
Tokai University School of Medicine
🇯🇵Kanagawa, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto, Japan
Kumamoto University Hospital
🇯🇵Kumamoto- shi, Japan
Kyoto University Hospital
🇯🇵Kyoto, Japan
Hiroshima University Hospital
🇯🇵Minami-ku, Japan
Nara Medical University Hospital
🇯🇵Nara, Japan
Hyogo College of Medicine College Hospital
🇯🇵Nishinomiya-shi, Japan
National Center for Global Health and Medicine
🇯🇵Shinjuku-ku, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Kindai University Hospital
🇯🇵Osaka, Japan
Osaka Metropolitan University Hospital
🇯🇵Osaka, Japan
Osaka University Hospital
🇯🇵Osaka, Japan
Saitama Medical University
🇯🇵Saitama, Japan
National Hospital Organization Hokkaido Cancer Center
🇯🇵Sapporo, Japan
National Cancer Center hospital
🇯🇵Tokyo, Japan
Tokyo Medical And Dental University, Medical Hospital
🇯🇵Tokyo, Japan
Showa University Hospital
🇯🇵Tokyo, Japan
Keio University Hospital
🇯🇵Tokyo, Japan
Yamaguchi University Hospital
🇯🇵Yamaguchi, Japan