Updated safety and long term clinical outcomes in TRANSCEND NHL 001, pivotal trial of lisocabtagene maraleucel (JCAR017) in R/R aggressive NHL.

JS Abramson, LI Gordon, ML Palomba, MA Lunning… - 2018 - ascopubs.org
JS Abramson, LI Gordon, ML Palomba, MA Lunning, JE Arnason, A Forero-Torres, M Wang
2018ascopubs.org
7505 Background: Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB
CAR T cell product administered in defined composition at a precise dose of CD8 and CD4
CAR T cells. A multicenter seamless design pivotal phase 1 trial of liso-cel in R/R B-NHL
(NCT02631044) has enrolled; long-term follow up of the nonpivotal cohort will be presented
here. Methods: Pts with R/R DLBCL, PMBCL, FL3B, or MCL and adequate organ function
are eligible. Treatment includes lymphodepletion with fludarabine and cyclophosphamide …
7505
Background: Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in defined composition at a precise dose of CD8 and CD4 CAR T cells. A multicenter seamless design pivotal phase 1 trial of liso-cel in R/R B-NHL (NCT02631044) has enrolled; long-term follow up of the nonpivotal cohort will be presented here. Methods: Pts with R/R DLBCL, PMBCL, FL3B, or MCL and adequate organ function are eligible. Treatment includes lymphodepletion with fludarabine and cyclophosphamide, followed by liso-cel. Multiple dose levels (DLs) and administration schedules were evaluated; DL2 (108 CAR T cells) was chosen for the pivotal cohort. The nonpivotal FULL dataset includes all pts in the DLBCL cohort (DLBCL NOS, PMBCL, FL3B) treated with liso-cel at all DLs; CORE dataset includes only pts meeting inclusion criteria for the pivotal cohort, including DLBCL NOS (de novo or transformed from FL) and high grade lymphoma. Study objectives include safety, PK, and antitumor response. Results: As of Oct 9, 2017, 91 pts were treated and evaluable for safety, 88 for efficacy. Pt characteristics were previously reported (Abramson ASH 2017). CRS was seen in 35% of pts; a single pt (1%) developed grade 3-4 CRS. Neurotoxicity (NT) developed in 19% of pts including 12% grade 3-4; all but one event resolved at time of data snapshot. Median onset of CRS and NT was 5 and 10 days respectively. Nineteen pts (21%) received tocilizumab and/or dexamethasone. Long term safety, including B cell aplasia, infections, and cytopenias, will be reported. Best ORR in FULL and CORE was 74% (65/88) and 80% (52/65), respectively; best CR was 52% (46/88) in FULL and 55% (36/65) in CORE. A higher rate of durable response at DL2 was observed in the CORE population, with 6-month ORR and CR of 50% and 50% (7/14) vs 40% (8/20) and 30% (6/20) at DL1. Long term efficacy, including 6-/12-month follow up from ~95/~55 pts, will be reported. Conclusions: Liso-cel shows durable responses in pts with heavily pretreated R/R DLBCL and trends toward more durable responses at DL2. Observed acute toxicities have been manageable at all DLs tested and long-term safety from the nonpivotal cohort will be reported. Clinical trial information: NCT02631044.
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