On October 1, the U.S. Food and Drug Administration (FDA) approved brexucabtagene autoleucel (Tecartus), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (ALL).
Efficacy was evaluated in ZUMA-3 (ClinicalTrials.gov identifier NCT02614066), a single-arm multicenter trial that evaluated brexucabtagene autoleucel in adults with relapsed or refractory B-cell precursor ALL. Patients received a single infusion of the agent following completion of lymphodepleting chemotherapy.
The efficacy outcome measures used to support approval were complete response achieved within 3 months from infusion and duration of complete response. Of the 54 patients evaluable for efficacy, 28 (52%; 95% confidence interval [CI] = 38–66) achieved complete response within 3 months. With a median follow-up for responders of 7.1 months, the median duration of complete response was not reached; the duration of complete response was estimated to exceed 12 months for more than half the patients.
The prescribing information for brexucabtagene autoleucel has a boxed warning for cytokine-release syndrome and neurologic toxicities. Cytokine-release syndrome occurred in 92% (grade ≥ 3, 26%) of patients and neurologic toxicities occurred in 87% (grade ≥ 3, 35%). The most common nonlaboratory adverse reactions (incidence ≥ 20%) included fever, cytokine-release syndrome, hypotension, encephalopathy, tachycardia, nausea, chills, headache, fatigue, febrile neutropenia, diarrhea, musculoskeletal pain, hypoxia, rash, edema, tremor, infection with pathogen unspecified, constipation, decreased appetite, and vomiting.
The recommended brexucabtagene autoleucel dose is a single intravenous infusion of 1 × 106 CAR-positive viable T cells per kg body weight (maximum 1 × 108 CAR-positive viable T cells), preceded by fludarabine and cyclophosphamide for lymphodepleting chemotherapy.
This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment. This application was granted Priority Review, Breakthrough Therapy designation, and Orphan Drug designation.