An Open-label, Randomized Phase 3 Study of MK-2870 as a Single Agent and in Combination With Pembrolizumab Versus Treatment of Physician's Choice in Participants With HR+/HER2- Unresectable Locally Advanced or Metastatic Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 1,200
- 试验地点
- 520
- 主要终点
- Progression-Free Survival (PFS) ( sacituzumab tirumotecan versus treatment of physician's choice [TPC]; pembrolizumab + sacituzumab tirumotecan versus TPC)
研究概览
简要总结
The purpose of this study is to compare sacituzumab tirumotecan as a single agent, and in combination with pembrolizumab, versus Treatment of Physician's Choice (TPC) in participants with hormone receptor positive/human epidermal growth factor receptor-2 negative (HR+/HER2-) unresectable locally advanced, or metastatic, breast cancer.
The primary hypotheses are that sacituzumab tirumotecan as a single agent and sacituzumab tirumotecan plus pembrolizumab are superior to TPC with respect to progression-free survival (PFS) per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) by blinded independent central review (BICR) in all participants.
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
- 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
- •Has unresectable locally advanced or metastatic centrally-confirmed hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) breast cancer
- •Has radiographic disease progression on one or more lines of endocrine therapy for unresectable locally advanced/metastatic HR+/HER2- breast cancer, with one in combination with a CDK4/6 inhibitor
- •Is a chemotherapy candidate
- •Has an eastern cooperative oncology group (ECOG) performance status of 0 to 1 assessed within 7 days before randomization
- •Has adequate organ function
- •Human immunodeficiency virus (HIV)-infected participants must have well controlled HIV on antiretroviral therapy
- •Participants who are Hepatitis B surface antigen (HBsAg) positive are eligible if they have received HBV antiviral therapy for at least 4 weeks, and have undetectable HBV viral load
- •Participants with a history of Hepatitis C virus (HCV) infection are eligible if HCV viral load is undetectable
排除标准
- •Has breast cancer amenable to treatment with curative intent
- •Has experienced an early recurrence (<6 months after completing adjuvant/neoadjuvant chemotherapy) and therefore is eligible to receive second-line (2L) treatment
- •Has symptomatic advanced/metastatic visceral spread at risk of rapidly evolving into life-threatening complications
- •Has received prior chemotherapy for unresectable locally advanced or metastatic breast cancer
- •Active autoimmune disease that has required systemic treatment in the past 2 years
- •History of (noninfectious) pneumonitis/interstitial lung disease that requires steroids, or has current pneumonitis/interstitial lung disease
- •Has an active infection requiring systemic therapy
研究组 & 干预措施
Arm A: Sacituzumab tirumotecan
Participants receive 4 mg/kg of sacituzumab tirumotecan once every 2 weeks (Q2W) via intravenous (IV) infusion until progressive disease or discontinuation.
干预措施: Sacituzumab tirumotecan (Drug)
Arm C: Treatment of Physician's Choice (TPC)
At the physician's discretion, participants receive chemotherapy of 80 mg/m^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.
干预措施: Capecitabine (Drug)
Arm C: Treatment of Physician's Choice (TPC)
At the physician's discretion, participants receive chemotherapy of 80 mg/m^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.
干预措施: Liposomal doxorubicin (Drug)
Arm C: Treatment of Physician's Choice (TPC)
At the physician's discretion, participants receive chemotherapy of 80 mg/m^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.
干预措施: Paclitaxel (Drug)
Arm C: Treatment of Physician's Choice (TPC)
At the physician's discretion, participants receive chemotherapy of 80 mg/m^2 of paclitaxel once every week (Q1W) via IV infusion OR 90 mg/m^2 of paclitaxel once every 4 weeks (Q4W) via IV infusion OR 100 mg/m^2 of nab-paclitaxel Q4W via IV infusion OR 1000 mg/m^2 of capecitabine every 3 weeks (Q3W) orally OR 50 mg/m^2 of liposomal doxorubicin once every 4 weeks (Q4W) via IV infusion, until progressive disease or discontinuation.
干预措施: Nab-paclitaxel (Drug)
Arm B:Pembrolizumab + Sacituzumab tirumotecan
Participants receive 4 mg/kg of sacituzumab tirumotecan Q2W via IV infusion until progressive disease or discontinuation PLUS 400 mg of pembrolizumab once every 6 weeks (Q6W) via IV infusion for up to 18 administrations (up to ~2 years).
干预措施: Pembrolizumab (Biological)
Arm B:Pembrolizumab + Sacituzumab tirumotecan
Participants receive 4 mg/kg of sacituzumab tirumotecan Q2W via IV infusion until progressive disease or discontinuation PLUS 400 mg of pembrolizumab once every 6 weeks (Q6W) via IV infusion for up to 18 administrations (up to ~2 years).
干预措施: Sacituzumab tirumotecan (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) ( sacituzumab tirumotecan versus treatment of physician's choice [TPC]; pembrolizumab + sacituzumab tirumotecan versus TPC)
时间窗: Up to ~38 months
PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented.
次要结局
- Overall Survival (OS)(Up to ~77 months)
- Change from baseline in diarrhea score, on the EORTC QLQ-C30(Baseline and up to ~77 months)
- Progression-Free Survival (PFS) (pembrolizumab + sacituzumab tirumotecan + versus sacituzumab tirumotecan)(Up to ~57 months)
- TTD in physical functioning score, on the EORTC QLQ-C30(Up to ~77 months)
- Number of participants who experience one or more adverse events (AEs)(Up to ~77 months)
- Change from baseline in physical functioning score, on the EORTC QLQ-C30(Baseline and up to ~77 months)
- Change from baseline in fatigue score, on the EORTC QLQ-C30(Baseline and up to ~77 months)
- Objective Response Rate (ORR)(Up to ~57 months)
- Change from baseline in global health status/quality of life scores, on the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline and up to ~77 months)
- Duration of Response (DOR)(Up to ~57 months)
- TTD in diarrhea score, on the EORTC QLQ-C30(Up to ~77 months)
- TTD in fatigue score, on the EORTC QLQ-C30(Up to ~77 months)
- Time to first Deterioration (TTD) in global health status/quality of life scores, on the EORTC QLQ-C30(Up to ~77 months)
- Change from baseline in emotional functioning score, on the EORTC QLQ-C30(Baseline and up to ~77 months)
- TTD in emotional functioning score, on the EORTC QLQ-C30(Up to ~77 months)
- Number of participants who discontinue study treatment due to an AE(Up to ~77 months)