A randomized phase II study of nab paclitaxel plus durvalumab plus neoantigen vaccine versus nab paclitaxel plus durvalumab in metastatic triple negative breast cancer (mTNBC).

TPS1114 Background: mTNBC is associated with poor outcomes and lacks targeted therapies. Immune modulation with PD-1/L1 inhibitors are emerging as effective anticancer therapies. In mTNBC, atezolizumab (anti-PD-L1) plus nab-paclitaxel demonstrated an improvement in PFS compared to nab-paclitaxel alone. Cancer vaccines targeting neoantigens may enhance the activity of immune checkpoint inhibition (ICI). Neoantigens are targets for CD8 T-cells following ICI. T-cell responses to neoantigens are high in affinity and are not limited by central mechanisms of self-tolerance. Next-generation sequencing and epitope prediction algorithms are used to identify/prioritize neoantigens for vaccine design and development. Preclinical studies have shown that neoantigen vaccines are well tolerated and may be synergistic with anti-PD-1/L1 therapy. Methods: Eligible mTNBC patients are randomized to either Arm-1 ( nab-paclitaxel + durvalumab + neoantigen vaccine) or Arm-2 ( nab-paclitaxel + durvalumab). Initially, all participants are treated with a run-in of gemcitabine + carboplatin (18-weeks; Part A). During this time sequencing and neoantigen vaccine production is performed. Subsequently, patients are treated with nab-paclitaxel + durvalumab + neoantigen vaccine vs. nab-paclitaxel + durvalumab (Part B). The neoantigen vaccine is given subcutaneously. Participants in Arm-1 receive vaccinations on Days 1, 4, 8, 15, 22, 50 and 78. Durvalumab is administered at 1500 mg IV every 4 weeks. Nab-paclitaxel is administered at 100 mg/m2 IV on Days 1, 8, and 15 of each 28-day cycle. Key eligibility criteria include patients with newly diagnosed mTNBC; measurable disease; and tumor accessible for biopsy. The primary endpoint is PFS defined as time from the initiation of Part B to progression or death. Secondary endpoints include safety, objective response rate, clinical benefit rate and OS. The exploratory endpoints include evaluating the immune response induced by the neoantigen vaccine, investigating biomarkers of response including TILs, PD-L1, and immune signature by gene expression, and mutational landscape. This trial is currently recruiting patients (NCT03606967).