High durable CR rates and preliminary safety profile for JCAR017 in R/R aggressive b-NHL (TRANSCEND NHL 001 Study): A defined composition CD19-directed CAR T-cell product with potential for outpatient administration.

120 Background: JCAR017 is a defined composition, CD19-directed 4-1BB CAR T cell product administered at a precise dose of CD8 and CD4 CAR T cells in a seamless design Phase 1 pivotal trial of relapsed/refractory (R/R) B-cell NHL (TRANSCEND NHL 001; NCT02631044). Methods: Patients (pts) with R/R DLBCL NOS, PMBCL, FL grade 3B, or MCL and adequate organ function are eligible. The FULL dataset includes all pts in the DLBCL cohort (i.e. excludes MCL). The CORE dataset includes pts meeting inclusion for a planned pivotal DLBCL cohort (DLBCL NOS de novo or transformed from follicular lymphoma, ECOG 0-1, no prior allo-SCT). Results: As of July 7, 2017, 69 pts were treated in the DLBCL cohort and evaluable for safety. In the FULL dataset, 21 pts (30%) had cytokine release syndrome (CRS), with 1 serious CRS event (1%; Gr 4). Neurotoxicity (NT) at any grade developed in 14 (20%), including 10 (14%) with Gr 3-4 events. There were no Gr 5 CRS or NT events. Median time to onset of first CRS and NT was 5 days and 10 days, respectively, 13 (19%) received anti-cytokine therapy and only one required vasopressor support. In the CORE dataset (n = 49), similar rates of CRS and NT were shown. The majority of pts, 64% (44/69), had no CRS or NT, and median onset of CRS and NT were 5 and 11 days, respectively, suggesting outpatient delivery of JCAR017 may be feasible. In the DLBCL cohort, 68 pts were evaluable for efficacy; best overall response, 3-month, and 6-month response rates in the FULL dataset were 75% (51/68), 49% (27/55), and 40% (14/35), respectively; and, in the CORE dataset, were 84% (41/49), 65% (26/40), and 57% (13/23). The best overall, 3-month, and 6-month CR rates were 61% (30/49), 53% (21/40), and 52% (12/23), respectively, in the CORE dataset. Among 16 double/triple hit pts, best ORR was 81%, and 3-month CR rate was 60%. A trend toward improved response rate at 3 months was observed in pts treated at DL2 compared to DL1. Conclusions: At the symposium, we will report updated efficacy and the preliminary safety profile for JCAR017, which supports potential outpatient administration in R/R Aggressive B-NHL patients. Clinical trial information: NCT02631044.