High Dose Radiation Therapy With Pembrolizumab and Chemotherapy for the Treatment of Patients With PD-L1 Positive Metastatic Triple Negative Breast Cancer

PRIMARY OBJECTIVE: I. To evaluate the 12 month progression-free survival (PFS) in PD-L1 positive, triple negative breast cancer patients treated with high dose radiotherapy before and concurrently with the first cycle of pembrolizumab plus chemotherapy. SECONDARY OBJECTIVES: I. To evaluate the objective response rate (ORR) in non-irradiated lesions nine weeks after the first dose of pembrolizumab in PD-L1 positive, triple negative breast cancer patients treated with high dose radiotherapy before and concurrently with the first cycle pembrolizumab plus chemotherapy (ORR per Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1). II. To determine if targeted, high dose radiotherapy to up to 3 metastatic sites in combination with pembrolizumab plus chemotherapy in patients with metastatic triple negative breast cancer (\> 2 sites) adversely increases the frequency and severity of toxicities associated with radiotherapy or pembrolizumab plus chemotherapy when administered separately. III. To determine progression-free survival (PFS) in breast cancer patients treated with high dose radiotherapy, pembrolizumab, and chemotherapy. EXPLORATORY OBJECTIVES: I. To collect, store, and analyze circulating tumor deoxyribonucleic acid (ctDNA) in metastatic breast cancer patients treated with radiotherapy, pembrolizumab, and chemotherapy to determine the relationship between ctDNA and PFS and ORR. II. To collect, store and analyze tumor tissue from a non-irradiated metastatic breast cancer site before and after radiotherapy to explore the immune tumor microenvironment and the immunoscore, and the relationship between the immunoscore and ORR and PFS in metastatic breast cancer patients treated with pembrolizumab and chemotherapy. OUTLINE: Patients undergo radiation therapy once every other day for 3 doses. Beginning within 48 hours of their first dose of radiation therapy, patients receive standard of care pembrolizumab intravenously (IV) on day 1 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also receive 1 of 3 standard of care chemotherapy options: nab-paclitaxel IV on days 1, 8, and 15 of each cycle, or paclitaxel IV on days 1, 8, and 15 of each cycle, or carboplatin IV and gemcitabine IV on days 1 and 8 of each cycle. Cycles of nab-paclitaxel and paclitaxel repeat every 28 days and cycles of carboplatin and gemcitabine repeat every 21 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo a biopsy at baseline and 2 weeks after radiation therapy and also undergo computed tomography (CT) scans, bone scans and blood sample collections throughout the trial. After completion of study treatment, patients are followed up every 12 weeks.