A Phase 2, Umbrella Study to Evaluate the Safety, Tolerability, and Clinical Activity of Investigational Agents for Newly Diagnosed, High-Risk, Early-Stage Triple-Negative Breast Cancer
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 入组人数
- 100
- 试验地点
- 2
- 主要终点
- Number of participants with one or more adverse events (AEs)
研究概览
简要总结
Researchers want to learn if giving boserolimab (MK-5890) with standard treatment (pembrolizumab and chemotherapy) before surgery can help treat triple negative breast cancer (TNBC). The goals of this study are to learn about the safety of boserolimab given with standard treatment before surgery and to learn if people tolerate it and how many people have no signs of cancer in the tissues and lymph nodes removed during surgery.
详细描述
The umbrella design of this study provides the framework to evaluate the safety, tolerability and clinical activity of different investigational agents in participants with newly diagnosed, high-risk, early-stage TNBC who might benefit from adding these investigational agents to pembrolizumab plus 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 tumor stage T1c, nodal stage N1-2, or tumor stage T2-4, nodal stage N0-2
- •Has provided a core needle biopsy for tissue diagnosis of the current breast cancer less than 29 days prior to the date of informed consent
- •Has centrally confirmed diagnosis of BC that is triple-negative based on the American Society of Clinical Oncology/College of American Pathologists guidelines
- •Has Eastern Cooperative Oncology Group performance status of 0 or 1 performed within 28 days before treatment randomization
- •Has left ventricle ejection fraction of ≥50% as assessed by echocardiogram or multigated acquisition scan performed at screening
- •Has a history of exposure to anthracycline; participants can be eligible after completion of a Sponsor consultation form, if cumulative lifetime doses are as follows: Doxorubicin <100 mg/m2, Epirubicin <180 mg/m2, Mitoxantrone <40 mg/m2, Idarubicin <22.5 mg/m
- •Note: If another anthracycline or more than one anthracycline has been used, the cumulative dose must not exceed the equivalent of 100 mg/m2 of doxorubicin
排除标准
- •The main exclusion criteria include but are not limited to the following:
- •Has documented Grade ≥2 peripheral neuropathy
- •Has uncontrolled or significant cardiovascular disease
- •Has received prior therapy with an anti-programmed cell death protein 1 (anti-PD-1), anti-programmed cell death-ligand 1 (anti-PD-L1), or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (e.g., cytotoxic T-lymphocyte-associated protein-4 [CTLA-4], OX-40 [cluster of differentiation (CD) 134], or CD137)
- •Has received any prior treatment, including radiation, systemic therapy, and/or definitive surgery for currently diagnosed breast cancer
- •Has received prior systemic anticancer therapy
- •Has undergone excisional biopsy of the primary tumor and/or axillary lymph node dissection prior to study treatment
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention
- •Has a known additional malignancy that is progressing or has required active treatment within the past 5 years
- •Has active autoimmune disease that has required systemic treatment in the past 2 years with need for disease modifying agents such as corticosteroids or immunosuppressive drugs
- •Has history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
- •Has an active infection requiring systemic therapy
- •HIV-infected participants with a history of Kaposi's sarcoma and/or Multicentric Castleman's Disease
- •Has severe hypersensitivity (Grade ≥3) to pembrolizumab, any investigational agent or study intervention, any of its excipients, and/or to another biologic therapy
- •Has a history of allogeneic tissue/solid organ transplant
研究组 & 干预措施
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Pembrolizumab (Biological)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Paclitaxel (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Carboplatin (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Doxorubicin (hydrochloride) (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Epirubicin Hydrochloride (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Cyclophosphamide (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Capecitabine (Drug)
Pembrolizumab+ Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Olaparib (if approved/available locally) (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Pembrolizumab (Biological)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Paclitaxel (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Carboplatin (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Doxorubicin (hydrochloride) (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Boserolimab (Biological)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Epirubicin Hydrochloride (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Cyclophosphamide (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Capecitabine (Drug)
Pembrolizumab+Boserolimab+Paclitaxel+ Carboplatin
Participants will receive pembrolizumab PLUS boserolimab PLUS paclitaxel PLUS carboplatin followed by pembrolizumab PLUS doxorubicin hydrochloride or epirubicin hydrochloride and cyclophosphamide PLUS boserolimab as neoadjuvant therapy prior to surgery. In adjuvant therapy participants will receive pembrolizumab PLUS optional additional adjuvant treatment of physician's choice (TPC), capecitabine or olaparib.
干预措施: Olaparib (if approved/available locally) (Drug)
结局指标
主要结局
Number of participants with one or more adverse events (AEs)
时间窗: Up to approximately 34 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Number of participants who discontinue study intervention due to an AE
时间窗: Up to approximately 27 months
An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment.
Pathological complete response (pCR) rate at the time of definitive surgery
时间窗: Up to approximately 9 months
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.
次要结局
- pCR-no ductal carcinoma in situ (DCIS) rate at the time of definitive surgery(Up to approximately 9 months)
- Event-Free Survival (EFS)(Up to approximately 72 months)
- Overall Survival (OS)(Up to approximately 72 months)