Zuma-6: Phase 1-2 multicenter study evaluating safety and efficacy of axicabtagene ciloleucel (axi-cel; KTE-C19) in combination with atezolizumab in patients with refractory diffuse large b-cell lymphoma (DLBCL).

Abstract

TPS7572 Background: Approximately 1/3 of patients with DLBCL, the most common type of B-cell lymphoma, will become refractory to standard combination chemotherapy and have uniformly poor clinical outcomes (Crump, ASCO 2016). Axi-cel (autologous anti-CD19 chimeric antigen receptor [CAR] T cell therapy) has shown promising response rates in patients with refractory DLBCL compared with standard approaches, although some patients do not respond or progress after an initial response (Locke, Mol Ther 2016). Expression of PD-L1 on DLBCL cells and activation-dependent expression of PD-1 on CAR T cells after infusion led to the hypothesis that PD-1 pathway blockade may augment the activity of axi-cel and result in improved clinical outcomes. This study will evaluate safety and efficacy of axi-cel when given with atezolizumab (anti–PD-L1 antibody), delivered sequentially, in patients with refractory DLBCL. Methods: Phase 1 will enroll ~3-9 patients to estimate the incidence of dose-limiting toxicities. Phase 2 will enroll ~22 patients to evaluate safety and efficacy, with a primary endpoint of complete response (CR) rate (Cheson 2007). Secondary endpoints include key efficacy outcomes such as objective response rate (CR+partial response [PR]), duration of response, progression-free and overall survival, and safety and biomarker outcomes. Eligible adult patients will have received prior adequate therapy (including anti-CD20 monoclonal antibody and an anthracycline-based regimen) and have an ECOG PS of 0-1 and adequate bone marrow and organ function. Patients with a history of Richter transformation, transformed follicular lymphoma, CNS disease, or active infection are not eligible. Patients will receive fludarabine 30 mg/m2/d and cyclophosphamide 500 mg/m2/d × 3 d, followed by a single infusion of axi-cel (target dose, 2 × 106anti-CD19 CAR T cells/kg) followed by atezolizumab 1200 mg given every 21 d for 4 doses (phase 1, first dose to occur 21, 14, and 1 d after axi-cel infusion in cohorts 1, 2, and 3, respectively). The study opened to accrual in September 2016. Clinical trial information: NCT02926833.