A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo in Patients With HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3)
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 入组人数
- 96
- 试验地点
- 51
- 主要终点
- Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
研究概览
简要总结
This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.
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
- •HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)
- •Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy
- •Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting
- •No more than two prior lines of therapy in the metastatic setting
- •Measurable disease per RESIST version 1.1
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
- •Life expectancy >= 6 months
- •Adequate hematologic and end-organ function
- •For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
- •For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm
排除标准
- •Prior treatment with trastuzumab emtansine in metastatic setting
- •History of exposure to cumulative doses of anthracyclines
- •Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible
- •Current Grade >= 3 peripheral neuropathy
- •Cardiopulmonary dysfunction
- •History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death
- •History of leptomeningeal disease
- •Active or history of autoimmune disease or immune deficiency
- •Active hepatitis B, hepatitis C and/or tuberculosis
- •Prior allogeneic stem cell or solid organ transplantation
- •Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment
- •Pregnancy or lactation
研究组 & 干预措施
Arm A: Trastuzumab Emtansine and Placebo
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor.
干预措施: Trastuzumab Emtansine (Drug)
Arm A: Trastuzumab Emtansine and Placebo
Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor.
干预措施: Placebo (Other)
Arm B: Trastuzumab Emtansine and Atezolizumab
Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor.
干预措施: Trastuzumab Emtansine (Drug)
Arm B: Trastuzumab Emtansine and Atezolizumab
Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor.
干预措施: Atezolizumab (Drug)
结局指标
主要结局
Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)
时间窗: Up to 28 months
PFS was defined as the time from randomization to the first occurrence of documented disease progression (PD), as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Median PFS was calculated using the Kaplan-Meier (KM) methodology. Data for participants without PD or death from any cause as of the data cut-off date were censored at the time of the last tumor assessment.
Overall Survival (OS)
时间窗: Up to 28 months
OS was defined as the time from the first dose of study treatment to the time of death from any cause. Participants who are alive as of the data cut-off date of the analysis were censored at the last known date they were alive. Participants with no post-baseline information were censored at the date of randomization plus 1 day. Median OS was calculated using the KM methodology.
次要结局
- Objective Response Rate (ORR)(Up to 28 months)
- Duration of Response (DOR)(Up to 28 months)
- PFS in Participants With Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1(Up to 28 months)
- OS in Participants With Baseline Brain Metastases(Up to 28 months)
- Central Nervous System (CNS) PFS as Determined by Investigator Using RECIST v1.1 in Participants With Baseline CNS Metastases(Up to 28 months)
- CNS PFS as Determined by Investigator Using RECIST v1.1 in Participants Without Baseline CNS Metastases(Up to 28 months)
- Percentage of Participants With Adverse Events (AEs)(Up to 28 months)