Radiation Therapy and M7824 in Treating Patients With Metastatic Hormone Receptor Positive, HER2 Negative Breast Cancer

PRIMARY OBJECTIVES: I. To determine the recommended phase II dose (RP2D) of M7824 and radiation therapy in patients with metastatic hormone receptor positive (HR+)/HER2 negative (-) breast cancer. II. To evaluate the safety and tolerability of M7824 and radiation therapy in patients with metastatic HR+/HER2- breast cancer. SECONDARY OBJECTIVES: I. To assess immunologic/molecular responses, specifically percentage (%) change in tumor-infiltrating lymphocytes (TIL) pre and post therapy to M7824 and radiation therapy in patients with HR+/HER2- metastatic breast cancer. II. To explore progression free survival (PFS) and overall survival (OS) to power future definitive trial. III. To evaluate the in-field and abscopal effect of treatment with anti-PD-L1/TGF-beta trap (M7824) and radiation therapy. EXPLORATORY OBJECTIVES: I. To characterize the effect of anti-PD-L1/TGF-beta trap (M7824) and radiation therapy on immune biomarkers including PD-L1 expression and fibrosis changes in tumor microenvironment in tumor tissue obtained from subjects pre- and post-treatment. II. To characterize circulating immune cell populations and cytokine profiles in tumor and circulation following treatment with M7824. III. To conduct ribonucleic acid sequencing (RNAseq), RNA Scope, whole exome sequencing (WES) targeted sequencing and tissue IO gene expression. OUTLINE: Patients receive M7824 intravenously (IV) over 1 hour every 14 days. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Beginning within 3 days after second dose of M7824, patients undergo radiation therapy once a day (QD) for 5-10 days depending on the site of disease in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up for 90 days.