This is a Phase II, single-arm, open label study to evaluate Olaparib plus Pembrolizumab following platinum-based chemotherapy plus Pembrolizumab as neoadjuvant therapy for germline BRCA (gBRCA) 1/2 mutated triple negative breast cancer (TNBC).
Pembrolizumab in combination with weekly paclitaxel and carboplatin (treatment 1) is followed by Pembrolizumab in combination with Olaparib (treatment 2) in neoadjuvant setting and Pembrolizumab in combination with Olaparib in adjuvant setting will be studied
Male/female subjects who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of invasive breast cancer
Have histologically confirmed TNBC, as defined by the most recent ASCO/CAP guidelines.
Confirmed germline BRCA 1/2 mutated.
T1c, N1-N2
Subjects who has a positive urine pregnancy test within 72 hours prior to registration
Has diagnosed as inflammatory breast cancer.
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 .
Has received a live vaccine or live-attenuated vaccine within 30 days prior to the first dose of study drug.
Single group
Pembrolizumab
Drug200 mg fixed dose, IV, every 3 weeks (Q3W), on Days 1 of Cycles 1-4
Paclitaxel
Drug80 mg/m2, IV, weekly, on Days 1, 8, 15 of Cycles 1-4
Carboplatin
DrugArea under the curve (AUC 1.5), intravenously (IV), weekly, on Days 1, 8, 15 of Cycles 1-4
Olaparib
Drug300 mg BID (twice daily) orally
Definitive Surgery
Procedure/SurgeryEach subject will undergo definitive surgery 3-6 weeks after conclusion of the last cycle of the neoadjuvant treatment.
Pathological Complete Response (pCR) Rate (ypT0/TisypN0)
Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.
Residual Cancer Burden 0/1
Residual Cancer Burden (RCB) 0/1 rate is defined as the proportion of subjects on evaluation from routine pathologic sections of the primary breast tumor and the regional lymph nodes after the completion of neoadjuvant therapy assessed by the local pathologist at the time of definitive surgery. Six variables are included in a calculation formula. The calculated RCB index value can also be categorized as one of four RCB classes (0 - 3). The calculation formula and detailed description can be found at a dedicated Web site: http://www.mdanderson.org/breastcancer\_RCB.
Pathological Complete Response (pCR) Rate (ypT0/is)
Pathological complete response rate (ypT0/is) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen regardless of regional lymph nodes status following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
Pathological complete response rate (ypT0/TisypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy by AJCC staging criteria (7th edition) assessed by the local pathologist at the time of definitive surgery.
Three-Year Overall Survival (3-year OS)
The Proportion of Three Year-Overall Survival (3y-OS) is defined as the proportion of survival subjects without death due to any cause at 3 years from registration. Subjects without documented death at the time of the analysis will be censored at the date of the last follow-up.
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Okayama University
Lead sponsor
Merck Sharp & Dohme LLC
Collaborator
