Veliparib and Atezolizumab Either Alone or in Combination in Treating Patients With Stage III-IV Triple Negative Breast Cancer

Brief description of study

This randomized phase II trial studies how well veliparib and atezolizumab work either alone or in combination in treating patients with stage III-IV triple negative breast cancer. Veliparib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Monoclonal antibodies, such as atezolizumab, may interfere with the ability of tumor cells to grow and spread. It is not known whether giving veliparib and atezolizumab either alone or in combination would work better in patients with triple negative breast cancer.

Clinical Study Identifier: NCT02849496

Detailed Study Description

PRIMARY OBJECTIVES: I. To compare the progression free survival (PFS) among three study arms, i.e., veliparib (ABT-888) monotherapy (arm 1), atezolizumab monotherapy (arm 2), and ABT-888 + atezolizumab in combination (arm 3) based on normal Response Evaluation Criteria in Solid Tumors (RECIST) criteria in patients with advanced triple negative breast cancer (TNBC) harboring homologous deoxyribonucleic acid (DNA) repair (HDR) through BRCA 1/2 mutation. SECONDARY OBJECTIVES: I. To compare the progression free survival (PFS) among the three study arms based on immune response criteria. II. To compare the time to treatment failure (TTF) among the three study arms based on immune response criteria and normal RECIST. III. To compare the overall response rate (ORR) among the three study arms based on immune response criteria and normal RECIST. IV. To compare the duration of response (DoR) among the three study arms based on immune response criteria and normal RECIST. V. Determine the changes in extent of mutational burden in BRCA 1/2 mutated tumors at baseline and at progression. VI. Evaluate and characterize changes in the extent of PD-L1 expression and tumor immune infiltrates. VII. Retrospectively evaluate tumors with limited immune infiltrate (e.g. "non-inflamed") to determine if PARPi increased immune infiltration. VIII. Determine the immune-related best overall response (irBOR) of ABT-888 in combination with atezolizumab in advanced TNBC harboring HDR through BRCA 1/2 mutation. TERTIARY OBJECTIVES: I. Evaluate changes in candidate neoantigen profiles and immune/inflammation signatures using DNA and ribonucleic acid (RNA)-sequencing in serial tumor biopsies. II. Evaluate and characterize immune parameters in peripheral blood/ peripheral blood mononuclear cell (PBMCs). III. Test the hypothesis that DNA repair status affects the tumor-immune interaction. IV. Characterize mechanism of action of the PARP inhibitor ABT-888. OUTLINE: Patients are randomized to 1 of 3 arms. ARM I: Patients receive veliparib orally (PO) twice daily (BID) on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to Arm III. ARM II: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients with disease progression may cross-over to Arm III. ARM III: Patients receive veliparib PO BID on days 1-21 and atezolizumab IV over 30-60 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for at least 4 weeks.

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