Phase II of Neoadjuvant Olaparib in Combination With Pembrolizumab in Patients With Triple Negative Breast Cancer (TNBC) or Hormone Receptor-positive HER2-negative Breast Cancer and Germline Mutations in DNA Damage Repair Genes
概览
- 阶段
- 2 期
- 干预措施
- Olaparib
- 疾病 / 适应症
- Breast Cancer
- 发起方
- Memorial Sloan Kettering Cancer Center
- 入组人数
- 23
- 试验地点
- 13
- 主要终点
- pathologically negative MRI-guided biopsy
- 状态
- 进行中（未招募）
- 最后更新
- 3个月前
概览
简要总结
This study will test any good and bad effects of combining the study drugs pembrolizumab and olaparib, given before the standard surgical procedure, to treat TNBC or HR+ HER2- breast cancers. The study drugs could shrink cancer, but they could also cause side effects. The study researchers want to find out whether the study drugs will shrink the cancer by a certain percentage compared with its current size, which may improve the outcome of surgery.
研究者
入排标准
入选标准
- •Signed Informed Consent Form
- •Ability to comply with protocol, in the investigator's judgment
- •Newly diagnosed histologically confirmed Stage T1c-3N0-3:
- •TNBC (ER/PgR negativity will be defined using IHC per ASCO/CAP criteria/HER2-negativity will be defined using ISH or IHC assays per ASCO/CAP criteria) OR
- •Hormone receptor-positive, HER2-negative breast cancer defined as per ASCO/CAP criteria
- •Measurable disease per RECIST v1.1
- •Minimum tumor size of 1.5 cm
- •All patients must have a germline mutation in BRCA1, BRCA2, PALB2, RAD51C, or RAD51D.
- •ECOG Performance Status of 0 or 1
- •Patient agreement to undergo appropriate surgical management including, if indicated, axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment. Note: consideration of neoadjuvant treatment will be determined by disease management team based on the subtypes and minimum size the tumor has to be.
排除标准
- •Prior history of invasive breast cancer
- •Stage IV (metastatic) breast cancer
- •Prior systemic therapy for treatment and prevention of breast cancer
- •Contraindication to MRI scan and/or allergy to intravenous contrast-gadolinium
- •Has 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 co-inhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137).
- •Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks. Note: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Participants with ≤Grade 2 neuropathy may be eligible. Note: If participant received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting study treatment.
- •Has received prior radiotherapy within 2 weeks of start of study treatment. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis.
- •Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
- •Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
- •Has a known additional malignancy that is progressing or has required active treatment within the past X 3 years prior to screening. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or cervical carcinoma in situ are not excluded. Patients with prior ductal/lobular carcinoma in situ are not excluded if they were treated exclusively with mastectomy \> 3 years prior to diagnosis of current breast cancer.
研究组 & 干预措施
Olaparib in Combination with Pembrolizumab
Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks in conjunction with olaparib (for the first 12 weeks) and cytotoxic chemotherapy (after olaparib has been completed) if administered prior to surgery and if the patient is not deemed to have tumor growth.
干预措施: Olaparib
Olaparib in Combination with Pembrolizumab
Pembrolizumab 400 mg will be administered as a 30 minute IV infusion every 6 weeks in conjunction with olaparib (for the first 12 weeks) and cytotoxic chemotherapy (after olaparib has been completed) if administered prior to surgery and if the patient is not deemed to have tumor growth.
干预措施: Pembrolizumab
结局指标
主要结局
pathologically negative MRI-guided biopsy
时间窗: 12 weeks
Biopsy-confirmed radiographic complete response will be determined at the 12-week timepoint. pCR/RCB0 will be determined at the time of surgery.