Background: Nivolumab (nivo) is a PD-1 immune checkpoint inhibitor that augments T-cell activation and host anti-tumor responses. PD-1 blockade has shown promise in B- and T-cell non-Hodgkin lymphoma (NHL),¹ but many patients (pts) with NHL do not respond or progress after response. Combination therapy using anti-tumor agents with complementary mechanisms of action and low immunosuppressive impact may result in more frequent and durable responses. Brentuximab vedotin (BV) is an anti-CD30 antibody?drug conjugate that induces cell cycle arrest and apoptosis, with activity in a range of NHL tumors.^2,3 Tumor cells undergoing BV-induced apoptosis have shown subsequent immune-mediated anti-tumor cytotoxicity.⁴ Therefore, nivo and BV may synergize if combined for relapsed/refractory (RR) NHL. Methods: CheckMate 436 (NCT02581631) is a phase 1?2, open-label, international, single-arm study evaluating nivo + BV for CD30-expressing RR NHL (study start: Dec 2015) in pts with RR diffuse large B-cell lymphoma, peripheral T-cell lymphoma (excluding anaplastic large cell lymphoma), and cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome); cohorts with primary mediastinal B-cell lymphoma (PMBL) and mediastinal gray zone lymphoma were made eligible in Sept 2016. Pts with PMBL must be aged ≥15 y (≥18 y for other histologies). All pts must have CD30-expressing disease, defined by CD30 on ≥1% of tumor cells or tumor-infiltrating lymphocytes by immunohistochemistry. In the phase 1 component, 6 pts will receive nivo and BV until disease progression or unacceptable toxicity. In the phase 2 component, ~130 more pts across the 5 histologies will be enrolled and treated at the recommended dose. Primary endpoints: safety, tolerability, and investigator-assessed objective response rate; secondary endpoints: duration of response and complete response (CR), CR rate, and progression-free and overall survival. Accrual is ongoing. References: 1. Lesokhin A et al. JCO 2016;34:2698?704 2. Jacobsen E et al. Blood 2015;125:1394?402 3. Horwitz S et al. Blood 2014;123:3095?100 4. Gardai S et al. Cancer Res 2015;75(15 Suppl):2469 [abstract]. Clinical trial information: NCT02581631