A Phase 3, Randomized, Open-label Study to Evaluate the Efficacy and Safety of Sac-TMT (Sacituzumab Tirumotecan, MK-2870) Followed by Carboplatin/Paclitaxel vs Chemotherapy, Both in Combination With Pembrolizumab as Neoadjuvant Therapy for High-Risk, Early-Stage, Triple-Negative Breast Cancer or Hormone Receptor-low Positive/Human Epidermal Growth Factor Receptor-2 Negative Breast Cancer
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 2,400
- 试验地点
- 329
- 主要终点
- Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery
研究概览
简要总结
Researchers are looking for new ways to treat types of breast cancer that are both:
- High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment
- Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone.
Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread.
The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy:
- Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy
- Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy
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
- •The main inclusion criteria include but are not limited to the following:
- •Has previously untreated high-risk, early-stage, non-metastatic (M0) breast cancer (BC), defined as any of the following combined primary tumor (T) and regional lymph node (N) staging per AJCC 8th edition criteria as assessed by the physician investigator based on radiological and/or clinical assessment:
- •cT1c, N1-N2
- •cT2, N0-N2
- •cT3, N0-N2
- •cT4a-d, N0-N2
- •The participant must have a centrally confirmed diagnosis of BC that is triple-negative or HR-low+/HER2- (defined as estrogen receptor (ER)-low+ expression in 1% to 10% cells and HER2- as by the most recent American Society of Clinical Oncology (ASCO)/College of American Pathologists (CAP) guidelines.
- •Provides a core needle biopsy from the primary breast tumor at screening to the central laboratory.
- •Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 performed within 28 days before Cycle1 Day 1 (C1D1).
- •Demonstrates adequate organ function.
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Metastatic (Stage IV) breast cancer or clinical node stage 3 (cN3) nodal involvement
- •Has received any prior treatment, including radiation, systemic therapy,and/or definitive surgery for currently diagnosed breast cancer
- •Has undergone excisional biopsy of the primary tumor, axillary lymph node dissection, and/or axillary sentinel lymph node biopsy prior to study treatment.
- •Received prior systemic anticancer therapy including investigational agents within 4 weeks before C1D
- •Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX- 40, CD137).
- •Received prior treatment with a TROP2-targeted antibody-drug conjugate (ADC).
- •Received prior treatment with a topoisomerase I inhibitor-containing ADC.
- •Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
- •Known additional malignancy that is progressing or has required active treatment within the past 5 years.
- •Uncontrolled systemic disease.
- •History of (noninfectious) pneumonitis/interstitial lung disease that required steroids, has current pneumonitis/interstitial lung disease or has suspected interstitial lung disease (ILD) or pneumonitis that cannot be ruled out by standard diagnostic assessments at Screening..
研究组 & 干预措施
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Sacituzumab tirumotecan (Biological)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Rescue Medication (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Paclitaxel (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Pembrolizumab (Biological)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Olaparib (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Pembrolizumab (Biological)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Doxorubicin (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Epirubicin (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Doxorubicin (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Cyclophosphamide (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Rescue Medication (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Capecitabine (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Cyclophosphamide (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Paclitaxel (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Epirubicin (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Olaparib (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Capecitabine (Drug)
sac-TMT
Participants receive sacituzumab tirumotecan intravenously (IV) at a dose of 4 mg/kg every 2 weeks (Q2W) + IV pembrolizumab 200 mg every 3 weeks (Q3W), for 12 weeks; then receive IV pembrolizumab 200 mg Q3W and IV carboplatin area under the curve (AUC) 1.5 + IV paclitaxel 80 mg/m^2 once weekly, for 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant treatment of physician's choice (TPC) may be administered to participants with residual disease. TPC options are olaparib 300 mg oral twice daily (BID) for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); capecitabine 1000-1250 mg/m^2 oral twice daily on days 1-14 and 22-35 each cycle for 4 six-week cycles; or doxorubicin 60mg/m^2 (or epirubicin 90 mg/m^2) IV infusion Q3W/Q2W + cyclophosphamide 600 mg/m^2 IV infusion Q3W/Q2W for 4 doses.
干预措施: Carboplatin (Drug)
Chemotherapy
Participants receive IV carboplatin AUC 1.5 and paclitaxel 80 mg/m^2 once weekly, alongside pembrolizumab 200 mg Q3W, for 6 weeks; then receive IV pembrolizumab 200 mg Q3W alongside IV cyclophosphamide 600 mg/m^2 Q3W and either doxorubicin 60 mg/m^2 Q3W or epirubicin 90 mg/m^2 Q3W, for up to 12 weeks. 3-6 weeks later, participants undergo surgery and optional radiation therapy, and receive IV pembrolizumab 400 mg once every 6 weeks or 200 mg Q3W for up to approximately 28 weeks. Additional adjuvant TPC may be administered to participants with residual disease. TPC options are olaparib 300 mg oral BID for 1 year (participants with germline breast cancer susceptibility gene mutation (gBRCAm) only); or capecitabine 1000-1250 mg/m^2 oral BID on days 1-14 and 22-35 each cycle for 4 six-week cycles.
干预措施: Carboplatin (Drug)
结局指标
主要结局
Percentage of Participants with Pathological Complete Response (pCR) at the Time of Definitive Surgery
时间窗: Up to approximately 30 weeks
pCR (ypT0/Tis ypN0) is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes after completion of neoadjuvant systemic therapy per current American Joint Committee on Cancer (AJCC) staging criteria assessed by the local pathologist at the time of definitive surgery.
Event-Free Survival (EFS)
时间窗: Up to approximately 92 months
EFS is defined as the time from randomization to disease progression that precludes surgery, local or distant recurrence, or death due to any cause, whichever occurs first.
次要结局
- Overall Survival (OS) (High-risk, early-stage, TNBC subset)(Up to approximately 115 months)
- Overall Survival (OS)(Up to approximately 115 months)
- Percentage of Participants with pCR with No Ductal Carcinoma in Situ (pCR-no DCIS) at the Time of Definitive Surgery(Up to approximately 30 weeks)
- Percentage of Participants with pCR at the Time of Definitive Surgery (High-risk, early-stage, TNBC subset)(Up to approximately 30 weeks)
- Event-Free Survival (EFS) (High-risk, early-stage, TNBC subset)(Up to approximately 92 months)
- Distant Progression or Distant Recurrence-Free Survival (DPDRFS)(Up to approximately 92 months)
- Change from Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) Global Health Status-Quality of Life Score(Baseline and up to approximately 3 years)
- Change from Baseline in EORTC QLQ-C30 Physical Functioning Score(Baseline and up to approximately 3 years)
- Change from Baseline in EORTC QLQ-C30 Role Functioning Score(Baseline and up to approximately 3 years)
- Change from Baseline in EORTC QLQ-C30 Fatigue Score(Baseline and up to approximately 3 years)
- Change from Baseline in EORTC QLQ Breast Cancer 42 (BR42) Systemic Therapy Side Effects Score(Baseline and up to approximately 3 years)
- Number of Participants Who Experience One or More Adverse Events (AEs)(Up to approximately 67 weeks)
- Number of Participants Who Discontinue Study Treatment Due to an AE(Up to approximately 54 weeks)