The purpose of this study is to find out whether adding pembrolizumab, with or without olaparib, to standard radiation therapy is a safe and effective treatment for metastatic breast cancer, , and to see whether the study treatment is better than, the same as, or worse than the usual approach (radiation therapy alone).
Female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of triple negative breast cancer or ER+/Her2 will be enrolled in this study.
Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 30 days prior to the date of allocation/randomization
Histologically or cytologically-confirmed TNBC (defined as ER <5%, PR <5%, HER- 2-neu 0-1+ by IHC or FISH-negative or per MD discretion).
Histologically of cytologically-confirmed ER+ breast cancer, defined as ER 1-100% and HER-2/neu 0-1+ by IHC or FISH-negative
Receipt of > 3 lines of systemic therapy in mTNBC patients
A WOCBP who has a positive urine pregnancy test within 72 hours or a serum pregnancy test within 14 days prior to treatment (see Appendix C). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
A minimum 2-week washout required for all anti-cancer agents, including cytotoxic chemotherapeutic agents, immunotherapy, biologic therapy, and targeted therapies. A 3-4 week washout is preferred when reasonable.
Note: in the event that 72 hours have elapsed between the screening pregnancy test and the first dose of study treatment, another pregnancy test (urine or serum) must be performed and must be negative in order for subject to start receiving study medication.
Parallel
Pembrolizumab
DrugPembrolizumab 200 mg will be administered as a 30 minute IV infusion every 3 weeks for 3 doses
Olaparib
DrugOlaparib will be administered twice daily continuously without breaks on a 21-day (3 week) cycle length, for a total of 2 cycles. Olaparib tablets will be administered bid (2 x 150 mg tablets twice daily; total 600 mg daily) on continuous days without interruption for 2 cycles. Each 3 week period constitutes one cycle.
Radiation
RadiationThe dose of radiation will be 8-9 Gy x 3 fractions. Radiation therapy will begin on C1D2-7. For tumors that are too large for this schedule, an accomodation of 30 Gy in 6 Gy per fraction is allowed, a schedule commonly used at MSK.
Overall Response Rate
To assess overall response rate (ORR) to pembrolizumab + , SBRT + /-olaparib, in non-targeted unirradiated lesions at 8 weeks using RECIST v1.1 in patients with mTNBC who have progressed on ICI or are PD-L1 negative and mER+BC.
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