6517 Background: Pts with R/R B-ALL and EMD have limited treatment options and are a population with an unmet need. Obe-cel is an autologous chimeric antigen receptor (CAR) T-cell therapy with a fast off-rate CAT19 binding domain and a 4-1BB-ζ co-stimulatory domain designed to improve persistence and reduce severe immunotoxicity. Here, we report a post-hoc analysis of the Phase Ib/II FELIX study (NCT04404660), evaluating efficacy and safety of obe-cel in pts with R/R B-ALL, by EMD status at lymphodepletion (LD). Methods: Following LD, adults with R/R B-ALL received obe-cel using a tumor burden-guided dosing strategy to minimize toxicity. Overall remission rate (ORR; complete remission [CR]/CR with incomplete hematologic recovery [CRi]), event-free survival (EFS), overall survival (OS), and safety are reported for pts with or without (w/o) EMD. Results: Of 127 obe-cel infused pts, 27 (21%) had EMD at LD and 100 (79%) did not. At screening, the median age (range) was 36.0 years (20–73) in pts with EMD, and 50.5 years (20–81) in pts w/o EMD. Of the pts with EMD, 13 (48%) were male and 11 (41%) were Hispanic or Latino; of those w/o EMD, 53 (53%) were male and 27 (27%) were Hispanic or Latino. The median number of prior lines of therapy (range) was 3.0 (1–6) and 2.0 (1–6) for pts with and w/o EMD at LD, respectively; prior SCT was received by 12 (44%) and 44 (44%) pts, respectively. At LD, the median bone marrow (BM) blast percentage (range) was 54% (0–100) in pts with EMD and 39% (0–100) in pts w/o EMD; Philadelphia chromosome-positive disease was observed in 6 (22%) and 30 (30%) pts, respectively. At 32.8 months’ (mos) median follow-up (range 20–53), the ORR (95% confidence interval [CI]) was 59% (39–78) in pts with EMD and 83% (74–90) in pts w/o EMD. Median DoR (95% CI) among responders was 42.5 mos (3.4–not evaluable [NE]) and NE, in those with (n=16) and w/o (n=83) EMD at LD, respectively. Overall, median EFS (95% CI) was 4.5 mos (0.0–NE) and 14.3 mos (9.0–NE) in pts with and w/o EMD at LD, respectively; however, median EFS appeared to be comparable in responders with (44.6 mos [6.0–NE]) and w/o EMD (NE). Overall, median OS (95% CI) was 15.3 mos (7.9–NE) and 21.0 mos (13.2–NE) in pts with and w/o EMD at LD, respectively. The incidence of Grade ≥3 cytokine release syndrome in pts with and those w/o EMD was 3.7% and 2.0%; the incidence of Grade ≥3 immune effector cell-associated neurotoxicity syndrome was 19% and 4.0%, respectively. Cerebrospinal fluid pharmacokinetic analyses are underway; data will be presented. Conclusions: Obe-cel treatment demonstrated favorable efficacy and safety outcomes in pts with and w/o EMD in the FELIX trial. Among responders, DoR in pts with EMD was comparable with that observed in pts w/o EMD. Overall, these findings support a positive benefit–risk profile for obe-cel, irrespective of EMD status at LD. Clinical trial information: NCT04404660 .
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