A Phase lb/ll, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of Venetoclax in Combination With Trastuzumab Emtansine in Patients With Previously Treated HER2-Positive Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 3
- 主要终点
- Phase II: Progression-Free Survival (PFS)
研究概览
简要总结
This two-part study is composed of two stages: a Phase Ib stage consisting of a dose-escalation phase and an expansion phase; and a Phase II, randomized, placebo-controlled, double-blind, multicenter stage. The Phase Ib stage will assess the safety and tolerability, determine the maximum tolerated dose (MTD) and the recommended Phase II dose (RP2D), and evaluate the preliminary efficacy of trastuzumab emtansine in combination with venetoclax in participants with previously treated human epidermal growth factor receptor 2 (HER2) positive unresectable locally advanced breast cancer (LABC) or metastatic breast cancer (MBC). Additional patients may be enrolled in an expansion phase to evaluate the safety, tolerability, and efficacy of trastuzumab emtansine in combination with venetoclax at RP2D in patients with previously treated HER2-positive LABC or MBC who have previously received either trastuzumab emtansine or trastuzumab deruxtecan (DS-8201a). The Phase II randomized stage will evaluate the safety, efficacy, tolerability, and pharmacokinetics of trastuzumab emtansine in combination with venetoclax at RP2D compared with trastuzumab emtansine plus placebo in participants with previously treated HER2-positive LABC or MBC who have not received prior trastuzumab emtansine therapy, either alone or in combination with other anti-cancer therapies.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation Phase
Participants received venetoclax in combination with a fixed dose of trastuzumab emtansine.
干预措施: Venetoclax (Drug)
Dose Escalation Phase
Participants received venetoclax in combination with a fixed dose of trastuzumab emtansine.
干预措施: Trastuzumab emtansine (Drug)
Dose Expansion Phase
Participants were to receive venetoclax at the Phase II Recommended Dose (RP2D) in combination with trastuzumab emtansine.
干预措施: Venetoclax (Drug)
Dose Expansion Phase
Participants were to receive venetoclax at the Phase II Recommended Dose (RP2D) in combination with trastuzumab emtansine.
干预措施: Trastuzumab emtansine (Drug)
Randomized Phase II Arm 1
Participants were to receive trastuzumab emtansine + placebo.
干预措施: Placebo (Drug)
Randomized Phase II Arm 1
Participants were to receive trastuzumab emtansine + placebo.
干预措施: Trastuzumab emtansine (Drug)
Randomized Phase II Arm 2
Participants were to receive trastuzumab emtansine + venetoclax.
干预措施: Venetoclax (Drug)
Randomized Phase II Arm 2
Participants were to receive trastuzumab emtansine + venetoclax.
干预措施: Trastuzumab emtansine (Drug)
结局指标
主要结局
Phase II: Progression-Free Survival (PFS)
时间窗: Up to 30 months
The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Dose Escalation: Number of Participants With Adverse Events
时间窗: Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks).
The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Expansion Phase: Objective Response Rate (ORR)
时间窗: Up to 30 months
The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
Phase II: ORR
时间窗: Up to 30 months
The study was terminated by the Sponsor. Only 1 participant was enrolled in this study. Based on the low enrolment number, no data is reported here in order to protect and maintain participant privacy/confidentiality.
次要结局
- Phase II: Serum Concentration of Trastuzumab Emtansine(At pre-defined time points from Cycle 1 Day 1 through Cycle 4 Day 1 (cycle = 21 days))
- All Phases: Plasma Concentration of Venetoclax(At pre-defined time points from Cycle 1 Day 8 and/or Cycle 2 Day 1 through Cycle 4 Day 1 (cycle = 21 days))
- Expansion Phase and Phase II: Duration of Response (DOR)(Up to 30 months)
- Phase II: Overall Survival (OS)(Randomization to death from any cause (up to 30 months))
- Expansion Phase and Phase II: Number of Participants With Adverse Events(Baseline up until 28 days after the last dose of study drug or until initiation of new systemic anti-cancer therapy, whichever occurs first (up to a maximum of 20 weeks).)
- Phase II: Number of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine(Up to 30 months)