FDA Greenlights Obe-cel in Relapsed/Refractory B-ALL

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• The FDA has approved obecabtagene autoleucel (obe-cel; Aucatzyl) as a treatment for adult patients with relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL).
• The agent showed a 77% response rate, with 96% of patients achieving measurable residual disease (MRD) negativity.
• The treatment also demonstrated a manageable safety profile, with only 2.4% of patients experiencing grade 3 or higher cytokine release syndrome (CRS).

The FDA approved the chimeric antigen receptor (CAR) T-cell therapy obe-cel for the treatment of adult patients with relapsed/refractory B-ALL.¹

Findings from the phase 1b/2 FELIX trial (NCT04404660) of obe-cel for the treatment of those with relapsed/refractory ALL support this approval. Data presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition showed that treatment with obe-cel elicited a complete response (CR) or CR with incomplete hematologic recovery (CRi) rate of 77% (n = 95/124) and a CR rate of 57% (n = 71/124).²

Additionally, 96% of patients with evaluable MRD status had MRD negativity based on central flow cytometry analysis. As of March 2023, the median duration of response had not yet been reached.

Grade 3 or higher CRS affected 2.4% of patients, and 7.1% had grade 3 or higher immune effector cell associated neurotoxicity syndrome (ICANS). Investigators reported that CAR T expansion was consistent across the phase 1b/2 cohorts and that CAR T was persistent in most responders at the time of follow up.

About the FELIX Study

The phase 1b/2 study enrolled patients relapsed/refractory B-ALL. Patients underwent lymphodepletion with fludarabine at 4 x 30 mg/m² and cyclophosphamide at 2 x 500 mg/m². Additionally, investigators administered obe-cel at a target dose of 410 x 10⁶CAR T cells as a split dose on days 1 and 10 as determined via prelymphodepletion bone marrow blast burden.

Enrollment was open to patients aged 18 years and older with relapsed/refractory B-cell ALL and an ECOG performance status of 0 or 1. Patients were required to have adequate renal, hepatic, pulmonary, and cardiac function and documented CD19 positivity within 1 month prior to screening. Patients with Philadelphia chromosome-positive ALL were eligible to enroll if they had intolerance to tyrosine kinase inhibitor (TKI) therapy, progressed on 2 lines of TKIs, or progressed on 1 line of therapy including a second-generation TKI.

The primary end point of the study was overall remission rate as assessed by independent review. Secondary end points included duration of remission, MRD-negative remission rate, safety, and CAR T expansion and persistence.

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://tinyurl.com/4wrjdjr8

2. Roddie C, Sandhu KS, Tholouli E, et al. Obecabtageneautoleucel (obe-cel, AUTO1) for relapsed/refractory adult B-cell acute lymphoblastic leukemia (R/R B-ALL): pooled analysis of the ongoing FELIX phase Ib/II study. Blood. 2023;142(suppl 1):222. doi:10.1182/blood-2023-179454