FDA Approves Obecabtagene Autoleucel for Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia

The FDA has granted regulatory approval to obecabtagene autoleucel (Aucatzyl; Autolus Inc), a CD19-directed genetically modified autologous T cell immunotherapy, to treat adults with relapsed or refractory (R/R) B-cell precursor acute lymphoblastic leukemia (ALL), according to a news release from the agency.¹

Obecabtagene autoleucel was evaluated in the FELIX trial (NCT04404660), an open-label, multicenter, single-arm study that enrolled adult patients with R/R CD19-positive B-cell ALL. Patients enrolled were required to have relapsed following a remission lasting 12 months or less, R/R ALL following 2 or more lines of systemic therapy, or disease that was R/R 3 or more months following allogenic stem cell transplantation.^1,2

Primarily, the investigators sought to evaluate the drug’s safety and efficacy by determining the rate and duration of complete remission (CR) achieved within 3 months following infusion, in addition to rate and duration of overall CR. Patients went through 5 stages in the trial: screening, leukapheresis, pre-conditioning, treatment, and follow-up.²

In total, 65 patients were evaluable for efficacy. Of these, 27 (42%; 95% CI, 29%-54%) achieved CR within 3 months, according to the study data. Furthermore, the median duration of CR achieved within 3 months was 14.1 months (95% CI, 6.1-not reached).¹

Safety data were also deemed positive for the drug. A pre-specified interim analysis of the trial, presented at the 2023 American Society of Clinical Oncology Annual Meeting, was conducted based on a total of 92 participants. Of these patients, 63% developed any-grade cytokine release syndrome (CRS), at a median of 9 days post-infusion and a median duration of 5 days. Additionally, any grade immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 23% of patients.³

More detailed safety data were released by the FDA, with the agency noting that the prescribing information for obecabtagene autoleucel contains a boxed warning for CRS, ICANS, and T-cell malignancies. In the full study population, CRS occurred in 75% of participants, with neurological toxicities occurring in. 64%, including ICANS in 24%.¹

Common non-laboratory adverse reactions—with an incidence of ≥ 20%--included CRS, pathogen-unspecified musculoskeletal pain, viral infections, nausea, fever, diarrhea, febrile neutropenia, ICANS, and headache, among others. In the interim analysis, febrile neutropenia was also observed, at a rate of 25%, in addition to anemia (20%).^1,3

In their announcement, the FDA wrote that the recommended dose of obecabtagene autoleucel is 410 X 106 CD19 chimeric antigen receptor (CAR)-positive viable T cells to be administered as split dose infusion on Day 1 and Day 10. The dose should be based on bone marrow blast assessment and follow fludarabine and cyclophosphamide lymphodepleting chemotherapy.¹

REFERENCES

1. FDA. FDA obecabtagene autoleucel for adults with relapsed or refractory B-cell precursor acute lymphoblastic leukemia. News Release. Released November 8, 2024. Accessed November 11, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-obecabtagene-autoleucel-adults-relapsed-or-refractory-b-cell-precursor-acute#:~:text=On%20November%208%2C%202024%2C%20the,acute%20lymphoblastic%20leukemia%20(ALL).

2. National Library of Medicine. A study of CD19 targeted CAR T cell therapy in adult patients with relapsed or refractory B cell acute lymphoblastic leukemia (ALL). ClinicalTrials.gov. Last updated September 3, 2024. Accessed November 11, 2024. https://clinicaltrials.gov/study/NCT04404660

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 Oncology. 2023;41(16). doi:10.1200/JCO.2023.41.16_suppl.7000