Testing the Addition of an Individualized Vaccine to Nab-Paclitaxel, Durvalumab and Tremelimumab and Chemotherapy in Patients With Metastatic Triple Negative Breast Cancer

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PRIMARY OBJECTIVE: I. Evaluate the clinical response to nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine (Arm 1) versus (vs.) nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab (Arm 2) in patients with metastatic triple negative breast cancer (TNBC). SECONDARY OBJECTIVE:...

PRIMARY OBJECTIVE: I. Evaluate the clinical response to nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine (Arm 1) versus (vs.) nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab (Arm 2) in patients with metastatic triple negative breast cancer (TNBC). SECONDARY OBJECTIVE: I. Evaluate the safety of nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine vs. nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab in patients with metastatic TNBC. EXPLORATORY OBJECTIVES: I. Assess the immune response induced by nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab + neoantigen vaccine vs. nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab in patients with metastatic TNBC. II. Biomarkers of response to therapy will be assessed based on the research biopsies performed at baseline, following the chemotherapy run-in (Part A) and following nab-paclitaxel + durvalumab (MEDI4736) + tremelimumab +/- neoantigen vaccine (Part B). OUTLINE: PART A: Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes and carboplatin IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for 6 cycles in the absence of disease progression or unacceptable toxicity. Beginning cycle 4, patients with progression of disease within the first 18 weeks may switch and receive nab-paclitaxel IV over 30 minutes on days 1, 8, and 15 for 2 cycles at the discretion of the treating physician. PART B: Patients are randomized to 1 of 2 arms. ARM I: Patients receive personalized synthetic long peptide vaccine and poly-ICLC subcutaneously (SC) on days 1, 4, 8, 15, 22, 50, and 78 in the absence of disease progression or unacceptable toxicity. Patients also receive tremelimumab IV over 60 minutes on day 1 of cycles 1-4, durvalumab IV over 60 minutes on day 1 and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM II: Patients receive tremelimumab IV over 60 minutes on day 1 of cycles 1-4, durvalumab IV over 60 minutes on day 1 and nab-paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months for 1 year, then annually thereafter.

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