Background: JCAR017 is a second-generation, CD19-directed, 4-1BB CAR T cell product comprising CD8 and CD4 CAR T cells in a 1:1 ratio. A multicenter phase 1 trial of JCAR017 in R/R B-cell NHL (NCT02631044) is underway. Methods: Patients with R/R DLBCL, PMBCL, FL grade 3B, or MCL and adequate organ function are eligible. There was no minimum ALC requirement for apheresis; no test expansion was required. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by JCAR017. Multiple dose levels (DLs)/administration schedules of JCAR017 are being evaluated. Study objectives include safety, PK, and antitumor response. Results: As of November 23, 2016, 28 patients have been treated and are evaluable for safety and efficacy. Nineteen were male, 9 female; 25 DLBCL, 2 MCL, and 1 FL grade 3B. Median age was 63 years (range 37-79), median number of prior therapies was 4 (range 1-8), 23 (82%) were refractory to their last chemotherapy, and 16 (57%) had prior transplant. No severe cytokine release syndrome (sCRS) was observed; 10 patients had grade 1-2 CRS (1 received tocilizumab). Five patients developed neurotoxicity, including 4 grade 3-4; all events resolved in the 4 patients who had adequate follow up. Median onset of CRS and neurotoxicity were 5 and 11 days, respectively. Four deaths after disease progression occurred, none related to JCAR017. In 20 patients treated at DL1 (5×10⁷ cells), the RR was 80% with 60% achieving CR. One patient with secondary CNS involvement achieved CR without neurotoxicity. JCAR017 was detected at 3 and 6 months in responding patients, including some who relapsed; higher mean peak levels were detected in patients with durable response at 3 months. Data on patients treated at DL2 (1×10⁸ cells), alternative dose schedules, tumor biopsy, and additional biomarkers will be presented. Conclusions: Treatment with JCAR017 results in high CR rate in patients with heavily pretreated R/R DLBCL. Relapses can occur despite persistence of JCAR017, suggesting tumor immune evasion mechanisms may contribute to relapse. Observed toxicities are manageable and occurred at rates lower than those reported for other CD19-directed CAR T cell products. Clinical trial information: NCT02631044