FDA Approves Obecabtagene Autoleucel for R/R B-Cell Precursor Acute Lymphoblastic Leukemia

FDA

The FDA has approved obecabtagene autoleucel (obe-cel; Aucatzyl) for the treatment of adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).

The regulatory decision was based on data from the phase 1/2 FELIX trial (NCT04404660). Findings showed that among evaluable patients (n = 65), the complete remission (CR) rate within 3 months of treatment was 42% (95% CI, 29%-54%). The median duration of CR for those who responded within 3 months was 14.1 months (95% CI, 6.1–not reached).

“Adult ALL is an extremely aggressive cancer, and there is a high unmet medical need that exists in the treatment of patients with this disease once they relapse, where historically they suffer from poor outcomes,” Elias Jabbour, MD, United States lead investigator of the FELIX study and professor of leukemia and ALL Section Chief at The University of Texas MD Anderson Cancer Center in Houston, stated in a news release.² “This milestone approval, based on the demonstrated clinical benefit of [obe-cel], brings new hope for adult patients with relapsed/refractory [B-cell] ALL.”

FELIX enrolled patients at least 18 years of age with relapsed/refractory B-cell ALL who had bone marrow blasts level of at least 5%.³

Following enrollment, patients were permitted to receive bridging therapy. On day –6, patients underwent lymphodepletion with 30 mg/m² of fludarabine for 4 days plus 500 mg/m² of cyclophosphamide for 2 days.

Obe-cel was given as a split-dose infusion on day 1 and day 10. For patients with a bone marrow blasts level of 20% or less, the day 1 infusion was 100 x 10⁶ CAR T cells; if patients did not experience grade 3 or higher cytokine release syndrome (CRS) or any-grade immune effector cell–associated neurotoxicity syndrome (ICANS), they received 310 x 10⁶ CAR T cells on day 10. For those with a bone marrow blasts level of more than 20%, the day 1 infusion was 10 x 10⁶ CAR T cells; the day 10 dose was 400 x 10⁶ CAR T cells if patients did not experience grade 3 or higher CRS or any-grade ICANS. Notably, 94% of infused patients received both doses during FELIX.

The study's primary end point was CR/CR with incomplete count recovery (CRi) rate. Secondary end points included duration of response (DOR), event-free survival, overall survival, minimal residual disease–negativity rate, and safety.

Topline data presented at the 2023 ASCO Annual Meeting showed evaluable patients (n = 94) achieved an overall response rate of 76% (95% CI, CI, 66%-84%; P < .0001). The CR and CRi rates were 54.3% and 21.3%, respectively. The median DOR was 14.1 months (95% CI, 5.9–not evaluable).

Safety data showed that the rate of any-grade CRS was 75%, and the grade 3 CRS rate was 3%.¹ Any-grade neurologic toxicities occurred in 64% of patients, including ICANS at a rate of 24%. The grade 3 rates of neurologic toxicities and ICANS were 12% and 7%, respectively.

The most common non-laboratory adverse effects reported in at least 20% of patients included CRS, infections-pathogen unspecified, musculoskeletal pain, viral infections, fever, nausea, bacterial infectious disorders, diarrhea, febrile neutropenia, ICANS, hypotension, pain, fatigue, headache, encephalopathy, and hemorrhage.

The prescribing information has a boxed warning for CRS, ICANS, and T-cell malignancies.

Obe-cel is recommended at a dose of 410 X 10⁶ CD19 CAR-positive T cells given as a split-dose infusion on days 1 and 10 (±2 days), based on bone marrow blast assessment. Lymphodepleting chemotherapy with fludarabine and cyclophosphamide is administered prior to the infusion of obe-cel.

References

1. FDA approves obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. FDA. November 8, 2024. Accessed November 8, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute
2. Autolus Therapeutics announces FDA approval of Aucatzyl (obecabtagene autoleucel – obe-cel) for adults with relapsed/refractory B-cell acute lymphoblastic leukemia (r/r B-ALL). News release. Autolus Therapeutics. November 8, 2024. Accessed November 8, 2024. https://autolus.gcs-web.com/news-releases/news-release-details/autolus-therapeutics-announces-fda-approval-aucatzylr
3. 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(suppl 16):7000. doi:10.1200/JCO.2023.41.16_suppl.7000