Safety and efficacy of obecabtagene autoleucel (obe-cel, AUTO1), a fast-off rate CD19 CAR, in relapsed/refractory adult B-cell acute lymphoblastic leukemia (r/r B-ALL): Top line results of the pivotal FELIX study.

Abstract

7000 Background: Obe-cel is an autologous CD19CAR with a fast off-rate CD19 binding domain designed to reduce CAR-T immunotoxicity and improve persistence. Its clinical activity has been tested in r/r paediatric and adult B-ALL trials (CARPALL, Ghorashian S et al., Nat Med 2019; ALLCAR19, Roddie C et al., JCO 2021) and more recently in adults with r/r B-cell malignancies (NCT02935257). Here, we present data from adult r/r B-ALL patients treated with obe-cel in the pivotal FELIX study (NCT04404660). Methods: FELIX is an open-label, multi-centre, global, single-arm Phase Ib/II study enrolling r/r B-ALL patients with morphological disease (≥5% BM blasts), measurable residual disease (MRD) (≥0.1% to < 5% BM blasts), or isolated extramedullary disease (Cohorts A, B and C). CAR-T products were generated using an automated closed process from fresh leukapheresate. Patients underwent bridging therapy as necessary and lymphodepletion with fludarabine (4x30mg/m2) and cyclophosphamide (2x500mg/m2). Patients received a target dose of 410E+6 CAR T cells as a split dose on Day 1 and Day 10. The dosing schedule is based on the % BM blasts performed locally prior to the pre-conditioning. Primary endpoint was overall remission rate (ORR) defined as proportion of patients achieving CR/CRi by central assessment. Results: As of 9th September 2022, a pre-specified interim analysis was conducted based on the first 50 patients infused in Cohort A who have been followed for 3 months or discontinued before month 3. The median age was 50 years (range 20-81), 22% had Ph+ B-ALL. The median number of prior lines of treatment was 2 (range 1-5), 42% underwent prior transplant. At screening, patients had a median of 55% BM blasts (range 6-96%) and 26% had EMD. The geometric mean of peak CAR expansion was 126147.6 copies/ug genomic DNA. Persistence was ongoing in majority of responders at last follow-up. Based on central assessment, the CR/CRi was 70% [95% CI: 55%, 82%] (p-value < 0.0001). As of 9th September 2022, a total of 92 patients received obe-cel and were evaluable for safety. 63% developed any grade CRS (3% Grade ≥3) at a median of 9 days post-infusion and a median duration of 5 days. Any grade ICANS was observed in 23% (8% Grade ≥3) at a median of 15 days post-infusion and of median duration 8 days. Other common Grade≥3 adverse events regardless of causality were febrile neutropenia (25%) and anaemia (20%). Conclusions: The pre-specified interim analysis of the FELIX study demonstrated that obe-cel for adult r/r B-ALL is safe with low rates of Grade >3 CRS and/or ICANS, even in patients with high burden disease. Obe-cel is effective with high CR/CRi rates and ongoing CAR T persistence in the majority of responders. The trial has completed dosing of all patients in Cohort A. Additional data and longer follow up will be reported at the conference. Clinical trial information: NCT04404660 .