The FDA has granted approval to obecabtagene autoleucel (obe-cel; Aucatzyl) for the treatment of adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL). This approval marks a significant advancement in the treatment landscape for this aggressive cancer, offering a new hope for patients who have failed to respond to conventional therapies.
The approval is based on the results of the phase 1b/2 FELIX trial (NCT04404660), which evaluated the efficacy and safety of obe-cel in patients with relapsed/refractory B-ALL. The data, presented at the 2023 American Society of Hematology (ASH) Annual Meeting and Exposition, demonstrated 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).
Key Findings from the FELIX Trial
In addition to the high response rate, 96% of patients with evaluable MRD status achieved MRD negativity based on central flow cytometry analysis. As of March 2023, the median duration of response had not yet been reached, indicating a potentially durable benefit for patients treated with obe-cel.
The safety profile of obe-cel was also notable. Grade 3 or higher CRS affected only 2.4% of patients, and 7.1% experienced grade 3 or higher immune effector cell-associated neurotoxicity syndrome (ICANS). These rates are considered manageable, especially in the context of CAR T-cell therapy, which is often associated with significant toxicities.
Trial Design and Patient Population
The phase 1b/2 FELIX study enrolled patients with relapsed/refractory B-ALL aged 18 years and older with an ECOG performance status of 0 or 1. Patients underwent lymphodepletion with fludarabine (4 x 30 mg/m2) and cyclophosphamide (2 x 500 mg/m2), followed by obe-cel administration at a target dose of 410 x 106 CAR T cells as a split dose on days 1 and 10. The primary endpoint of the study was overall remission rate as assessed by independent review. Secondary endpoints included duration of remission, MRD-negative remission rate, safety, and CAR T expansion and persistence.
Implications for B-ALL Treatment
This approval of obe-cel represents a significant step forward in the treatment of relapsed/refractory B-ALL. The high response rates, coupled with a manageable safety profile, make it an attractive option for patients who have limited treatment alternatives. The achievement of MRD negativity in a high proportion of responders further suggests the potential for long-term disease control. "The agent showed a 77% response rate, with 96% of patients achieving measurable residual disease (MRD) negativity," according to the study data.
Obe-cel offers a much-needed new therapeutic option for adult patients facing the challenges of relapsed/refractory B-ALL. Its approval is based on compelling clinical trial data demonstrating both efficacy and safety, providing hope for improved outcomes in this difficult-to-treat patient population.
