FDA Approves Obecabtagene Autoleucel in B-Cell ALL

Results from the FELIX trial support the approval of obecabtagene autoleucel in B-cell ALL.

The FDA has approved obecabtagene autoleucel (obe-cel; Aucatzyl) for patients with relapsed/refractory B-cell precursor acute lymphoblastic leukemia (ALL), according to a press release from the FDA.¹

The approval is based on results from the phase 1/2 FELIX trial (NCT04404660) assessing patients with CD19-positive B-cell ALL.² Topline data included a complete response (CR) in 42% (95% CI, 29%-54%) of patients within 3 months. The median duration of CR within 3 months was 14.1 months (95% CI, 6.1-not reached).

"I'm very thrilled that the FDA approved [obe-cel] for ALL therapy. In ALL, once you relapse, the outcome is not so great; I think [obecabtagene autoleucel] fills a major need," trial investigator Elias Jabbour, MD, a professor of medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center, stated in an interview with CancerNetwork^® on the approval.

"There's an unmet need in what to do for [patients who are] relapsed/refractory. Do we give them a salvage therapy regimen or [prepare them] for transplantation? I think [obe-cel] has shown to be extremely effective....It's too early to say, but what has been seen so far is promising in that [obe-cel may] replace transplants in a way that will induce durable remissions. But time will tell if what I'm saying will hold true," Jabbour added.

Patients on the trial must have relapsed after remission of 12 months or less, relapsed/refractory ALL after 2 or more lines of systemic therapy, or relapsed/refractory disease 3 or more months after allogeneic stem cell transplant.

A boxed warning for cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and T-cell malignancies for obe-cel were highlighted in the press release. A total of 75% of patients experienced CRS, with 3% having grade 3. Neurologic toxicities occurred in 64% of patients, with 12% having grade 3 or higher and 24% having ICANS with 7% being grade 3 or higher.

Currently, the recommended dose of obe-cel is 410x10⁶ CD19 CAR-positive viable T cells that will be administered as a split dose infusion on days 1 and 10 plus or minus 2 days. Additionally, a bone marrow blast assessment preceded by fludarabine and cyclophosphamide lymphodepleting chemotherapy will occur.

References

1. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. News release. FDA. November 8, 2024. Accessed November 8, 2024. https://shorturl.at/PIUIf
2. Roddie C, Sandhu KS, Tholouli E, et al. 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. J Clin Oncol. 2023;41(16). doi:10.1200/JCO.2023.41.16_suppl.7000