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TPS3102 Background: Multiple myeloma (MM) is largely incurable despite available therapies, including immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), and monoclonal antibodies (mAbs). As most MM patients (pts) eventually have relapsed/refractory (RR) disease, there is an unmet need. Myeloma cells upregulate PD-L1 [Liu et al, 2007]. Nivolumab (nivo), an immuno-oncology mAb, binds PD-1 on T cells and natural killer cells and inhibits signaling by PD-L1–expressing tumor cells, thus augmenting antitumor immunity. Nivo monotherapy has shown acceptable safety and modest clinical activity in RRMM [Lesokhin et al 2016]. Daratumumab (dara) is a cytolytic mAb that targets CD38+ myeloma cells, inducing antibody‐dependent cellular cytotoxicity, complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and apoptosis, and may have an immunomodulatory role via depletion of CD38+ immune-suppressor cells [Dimopoulos et al 2016]. Dara is approved as monotherapy (US: after ≥3 prior lines of therapy; EU: after a prior PI and IMiD and progression on last therapy), and with lenalidomide/dexamethasone (dex) or bortezomib/dex (US: after ≥1 prior line of therapy for both combinations). Combining PD-1 and CD38 mAbs, immunotherapies with different mechanisms of action, may overcome resistance and improve outcomes. This phase 1 safety study (NCT01592370) includes multiple cohorts of nivo as monotherapy or in combination regimens across RR hematologic malignancies; 2 MM cohorts will evaluate nivo plus dara, with or without pomalidomide and dex. Methods: Eligible pts are aged ≥18 y, with RRMM after ≥2 prior therapies. Pts are RR to their last regimen, RR to prior IMiD and PI therapy, and agreed to bone marrow aspiration. Primary outcome of safety/tolerability will be measured by incidence of drug-related adverse events (AEs), serious AEs, and laboratory test abnormalities. Secondary endpoints include minimal residual disease, overall response rates and duration of response, and progression-free survival. Study funding: BMS. Writing support: C Tomas, Caudex, funded by BMS. Clinical trial information: NCT01592370.