Background: Nivolumab (nivo) is a fully-human immunoglobulin G4 monoclonal antibody immune checkpoint inhibitor that targets programmed death receptor-1 (PD-1) to restore active T-cell immune responses against the tumor. While PD-1 blockade has shown encouraging activity in aggressive B-cell and T-cell NHL,¹ the majority of patients (pts) either do not respond or progress after an initial response. Combination therapy with therapeutic agents such as antibody-drug conjugates may increase the frequency and durability of responses, through both direct cell killing and immunogenic consequences of cell death. Brentuximab vedotin (BV) is a CD30-directed antibody-drug conjugate that has shown anti-tumor activity in a wide range of lymphoid malignancies. BV works primarily by inducing cell cycle arrest and apoptotic death in CD30-expressing cells. As BV may also mediate immunogenic cell death, it could synergize with PD-1 blockade.² We hypothesize that nivo and BV may induce frequent and durable responses in pts with CD30+ relapsed, refractory T-cell NHL and diffuse large B-cell lymphoma (DLBCL). Methods: This phase 1/2 open-label, international, multicenter study (NCT02581631), investigates the safety and efficacy of nivo combined with BV in pts with relapsed/refractory NHL. Pts (aged ≥ 18 yrs) with relapsed/refractory DLBCL, peripheral T-cell lymphoma (excluding anaplastic large cell lymphoma), or cutaneous T-cell lymphoma (mycosis fungoides/Sézary syndrome) are eligible. All pts must have expression of CD30 on ≥ 1% of tumor cells (by IHC analysis). In the ph1 portion, pts will receive nivo + BV with dose de-escalation for excessive toxicity. In the ph2 portion, an extra 90 pts will be enrolled across the 3 histologic subgroups. Primary endpoints: safety, tolerability, and objective response rate. Secondary endpoints: duration of response, complete response rate, duration of complete response, progression-free survival, overall survival, and biomarker analyses. Accrual is ongoing. References: 1. Armand P et al. Haematologica 2015;100(Suppl 1):S808 [abstract] 2. Gardai SJ et al. Cancer Res 2015;75(15 Suppl):2469 [abstract] Clinical trial information: NCT02581631