Comparison of Obecabtagene Autoleucel (obe-cel) Versus an External Control Arm (ECA) in Adult Patients (pts) with Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia (R/R B-ALL)
Year: 2025
Type: article
Abstract: Introduction The single-arm, Phase Ib/II FELIX study (NCT04404660) is evaluating the efficacy and safety of obe-cel, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult R/R B-ALL. Comparative analysis can be implemented to contextualize investigational trials when therapies are not directly compared in randomized studies. Objective To report efficacy and safety outcomes of obe-cel in FELIX pts vs pts treated with non-CAR T-cell standard of care (SOC) therapies in a matched ECA. Methods This prospectively designed, non-interventional study utilized pt data from FELIX (pts with ≥5% bone marrow blasts at screening; morphologic cohort; data cut-off: February 7, 2024) and pt-level data from historical clinical trials in the Medidata Enterprise Data Store database. Efficacy and safety outcomes were compared in pts treated with obe-cel (modified intent-to-treat [mITT]) and all enrolled pts (ITT) vs matched ECA pts treated with SOC (≥1 dose of blinatumomab , inotuzumab ozogamicin , or salvage chemotherapies). Matched cohorts were derived using a propensity score-based approach balancing baseline characteristics and prognostic factors . Primary endpoint was overall remission rate (ORR); secondary endpoint was overall survival (OS); event-free survival (EFS) and safety were exploratory endpoints. Results In the FELIX morphologic cohort, 94/112 enrolled pts received obe-cel infusion; 84 pts were matched to ECA pts treated with SOC for mITT analysis. Baseline characteristics between matched pts were generally balanced (Table 1). ORR was significantly higher with obe-cel vs SOC: 79.8% vs 54.8%, with a rate difference of 25.0% (95% confidence interval [CI]: 9.4−38.6; p=0.0009) and odds ratio of 3.3 (95% CI: 1.6−6.5). OS was significantly longer with obe-cel vs SOC when censoring allogeneic stem cell transplantation (SCT): 15.5 vs 10.2 months (mos), hazard ratio (HR) 0.52 (95% CI: 0.32−0.82; p=0.0046). Without SCT censoring, a trend for longer OS with obe-cel vs SOC was also observed: 14.2 vs 10.5 mos, HR 0.70 (95% CI: 0.47−1.05; p=0.0808). EFS was significantly longer with obe-cel vs SOC: 9.1 vs 2.8 mos, HR 0.43 (95% CI: 0.29−0.66; p<0.0001) and 9.0 vs 2.8 mos, HR 0.45 (95% CI: 0.32−0.66; p<0.0001), with and without SCT censoring, respectively. ITT analysis (n=107; Fig 1) showed similar results; however, OS was significantly longer for obe-cel vs SOC without SCT censoring: HR 0.70 (95% CI: 0.50−0.99; p=0.0430). In the mITT analysis, Grade ≥3 cytokine release syndrome and infection rates within 3 months of treatment initiation were comparable with obe-cel vs SOC: 3.6% vs 3.6% and 26.2% vs 28.6%, respectively. Conclusion Obe-cel demonstrated higher ORR and longer OS and EFS vs SOC in matched ECAs. Safety was comparable between treatment groups, demonstrating a positive benefit-risk profile of obe-cel for treatment of adult R/R B-ALL.
Institutions: Universitätsklinikum Würzburg, Moffitt Cancer Center, The University of Texas MD Anderson Cancer Center, Memorial Sloan Kettering Cancer Center, Methodist Healthcare, University of California, San Francisco, City Of Hope National Medical Center, University of California, Davis, University of Chicago, Dana-Farber Cancer Institute, Medidata (United States), University College London
Language: English
Topic: CAR-T cell therapy research
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,650
OpenAlex ID: W4407976845