Background: Mantle cell lymphoma (MCL) is an aggressive B cell malignancy, and accounts for ≈6% of non-Hodgkin lymphomas. Despite high initial response rates, MCL is generally considered incurable, as almost all patients (pts) eventually progress (Cheah et al. J Clin Oncol. 2016). Bruton tyrosine kinase (BTK) inhibition can lead to high rates of prolonged responses in relapsed/refractory (R/R) MCL, as noted with ibrutinib (Wang et al. NEJM. 2013) and acalabrutinib (Wang et al. Lancet. 2017). However, many pts develop ibrutinib-resistance and outcomes to salvage regimens (including investigational agents) are poor with a response rate of 32% and median overall survival of 8.4 months (Cheah et al. Ann Oncol. 2015). This phase 2, multicenter, open-label study examines efficacy and safety of KTE-C19, an autologous anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in pts with R/R MCL who have progressed on prior chemotherapy, an anti-CD20 antibody, and a BTK inhibitor. Methods: ZUMA-2 (NCT02601313) is enrolling pts with R/R MCL sequentially into 2 separate dose level cohorts (~40 pts each). After leukapheresis and manufacturing, pts will receive conditioning chemotherapy with fludarabine 30 mg/m²/d and cyclophosphamide 500 mg/m²/d × 3 d and then receive a single infusion of KTE-C19 cells at a dose of 0.5 × 10⁶ CAR T cells/kg. The primary endpoint is objective response rate by Independent Review Committee assessment; secondary and exploratory endpoints include duration of response, progression-free survival, overall survival, incidence of adverse events and levels of CAR T cells and cytokines in blood. Eligible adult pts with pathologically confirmed R/R MCL and an ECOG of 0-1 must have received ≤ 5 prior therapies that must have included an anthracycline or bendamustine-containing chemotherapy, anti-CD20 monoclonal antibody therapy, and ibrutinib or acalabrutinib. Pts who received allogenic stem cell transplant or prior CD19-directed therapy or those with clinically significant infection or a history of central nervous system lymphoma or central nervous system disorders are not eligible. Accrual is ongoing. Clinical trial information: NCT02601313