A Phase 1/2, Open-label Study of Sacituzumab Govitecan Administered at an Alternative Dose and Schedule in Participants With Advanced Triple-Negative Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 100
- 试验地点
- 22
- 主要终点
- Phase 1: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
研究概览
简要总结
The goal of this clinical study is to learn more about the study drug sacituzumab govitecan-hziy (SG) given at an alternative dose and schedule, in participants with triple-negative breast cancer (TNBC).
The primary objectives of this study are to assess the safety and tolerability of SG given at alternate dose and schedule, to assess the effect on objective response rate (ORR) and progression-free survival (PFS).
详细描述
Phase 1 of this study will evaluate the preliminary safety, tolerability, pharmacokinetics (PK), and efficacy of SG. Phase 2 expansion of this study will further evaluate the safety, efficacy, and PK of SG.
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
- •Individuals assigned male or female at birth, 18 years of age or older, able to understand and give written informed consent.
- •Histologically or cytologically locally confirmed TNBC.
- •Phase 1: Individuals with unresectable, locally advanced or metastatic TNBC who are refractory to or relapsed after at least one prior standard-of-care chemotherapy regimen or systemic therapy given for locally advanced or metastatic disease.
- •Phase 2: Individuals with unresectable, locally advanced or metastatic TNBC who have not received previous systemic therapy for advanced disease.
- •Phase 2: Tumors must be PD-L1 negative, defined as tumor PD-L1 combined positive score (CPS) < 10 using the PD-L1 immunohistochemistry (IHC) 22C3 assay. Alternatively, individuals with tumor CPS ≥ 10 will be eligible if they received an anti-PD-(L)1 agent (ie, checkpoint inhibitor) in the adjuvant or neoadjuvant setting or if they cannot be treated with an anti-PD-(L)1 agent. due to a comorbidity.
- •Uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) genotype status.
- •During Phase 1 safety run-in, individuals must be UGT1A1 wild-type.
- •After Phase 1 safety run-in, individuals with any UGT1A1 genotype may be eligible.
- •Measurable disease by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST Version 1.1 criteria.
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Adequate hematologic counts within 2 weeks prior to enrollment.
- •Adequate hepatic and renal function.
排除标准
- •Prior treatment with a topoisomerase 1 inhibitor or antibody-drug conjugate (ADC) containing a topoisomerase inhibitor.
- •Prior treatment with a trophoblast cell-surface antigen 2 (Trop-2)-directed ADC.
- •Note: Other protocol defined Inclusion/Exclusion criteria will apply.
研究组 & 干预措施
Phase 1
Participants will receive SG until progressive disease (PD), death, unacceptable toxicity, or another treatment discontinuation criterion is met.
干预措施: Sacituzumab Govitecan-hziy (SG) (Drug)
Phase 2: Expansion
Participants will receive SG until PD, death, unacceptable toxicity, or another treatment discontinuation criterion is met.
干预措施: Sacituzumab Govitecan-hziy (SG) (Drug)
结局指标
主要结局
Phase 1: Percentage of Participants Experiencing Dose-Limiting Toxicities (DLTs)
时间窗: First dose up to 28 days
Phase 1 and 2: Percentages of Participants Experiencing Adverse Events (AEs)
时间窗: First dose up to 30 days post last dose (Up to 3 years)
Phases 1 and 2: Percentages of Participants Experiencing Laboratory Abnormalities
时间窗: First dose up to 30 days post last dose (Up to 3 years).
Phases 1 and 2: Percentages of Participants Experiencing AEs Leading to Dose Reductions, Dose Interruptions, and Treatment Discontinuations
时间窗: First dose up to 30 days post last dose (Up to 3 years).
Phases 1 and 2: Objective Response Rate (ORR)
时间窗: Up to 9 months
ORR is defined as the proportion of participants who achieve a complete response (CR) or partial response (PR) that is confirmed at least 4 weeks after initial documentation of response as assessed by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1.
Phase 2: Progression-Free Survival (PFS)
时间窗: Up to 9 months
PFS is defined as the time from the date of the first SG dose until the date of progressive disease (PD) as assessed by the investigator according to RECIST Version 1.1, or death from any cause, whichever occurs first.
次要结局
- Phases 1 and 2: Serum Concentrations of SG(Up to End of Treatment (3 years))
- Phase 1 and 2: Percentage of Participants who Develop Antidrug Antibodies (ADAs) Against SG(First dose up to 30 days post last dose (Up to 3 years).)
- Phase 2: Duration of Response (DOR)(First dose up to 30 days post last dose (Up to 3 years).)
- Phase 2: Disease Control Rate (DCR)(Up to 9 months)