A Phase 1/2 Open-Label Study of Sacituzumab Govitecan in Japanese Patients With Advanced Solid Tumors (ASCENT-J02)
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 135
- 试验地点
- 42
- 主要终点
- 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
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Sacituzumab Govitecan-hziy, Metastatic Triple-negative Breast Cancer (mTNBC)
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy 8 mg, Advanced Solid Tumors
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy 6 mg, Advanced Solid Tumors
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy 10 mg, Advanced Solid Tumors
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy 6 mg, UGT1A1 Polymorphism
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy 10 mg, UGT1A1 Polymorphism
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy, HR+/HER2- Metastatic Breast Cancer (HR+/HER2- mBC)
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
Sacituzumab Govitecan-hziy, Metastatic Urothelial Carcinoma (mUC)
(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.
干预措施: Sacituzumab Govitecan-hziy (Drug)
结局指标
主要结局
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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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
时间窗: 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)
次要结局
- Phase 1: Pharmacokinetic (PK) Parameter: Cmax of Sacituzumab Govitecan-hziy (SG) and Free SN-38(Up to 33 months)
- Phase 1: PK Parameter: Tmax of SG and Free SN-38(Up to 33 months)
- Phase 1: PK Parameter: AUC0-168h of SG and Free SN-38(Up to 33 months)
- 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)
- Phase 2 (All Cohorts): ORR as Assessed by Investigator(Up to 17 months)
- Phase 2 (All Cohorts): Overall Survival (OS)(Up to 33 months)
- Phase 2 (All Cohorts): Duration of Response (DOR) as Assessed by Investigator(Up to 33 months)
- Phase 2 (All Cohorts): Time to response (TTR) as Assessed by Investigator(Up to 17 months)
- Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Progression-free survival (PFS) as Assessed by IRC(Up to 33 months)
- Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Duration of Response (DOR) as Assessed by IRC(Up to 33 months)
- Phase 2 (mTNBC and HR+/HER2- mBC Cohorts): Time to response (TTR) as Assessed by IRC(Up to 17 months)