Application for Brexucabtagene Autoleucel in B-cell ALL Submitted to FDA for Consideration


CD19-directed CAR T-cell therapy brexucabtagene autoleucel will be considered by FDA for indication in adults with B-cell precursor acute lymphoblastic leukemia.

A supplemental biologics license application has been submitted to the FDA for the chimeric antigen receptor (CAR) T-cell therapy brexucabtagene autoleucel (Tecartus) as therapy for adult patients with B-cell precursor acute lymphoblastic leukemia (ALL), according to the agent’s developer Kite, a Gilead Company.

The proposed indication is supported by data from the single-arm, phase 1/2 ZUMA-3 trial (NCT02614066) which is examining the CD19-directed therapy for safety and efficacy in patients with relapsed/refractory B-cell precursor ALL.

Previously, brexucabtagene autoleucel received FDA accelerated approval in July 2020 as therapy for patients with relapsed or refractory mantle cell lymphoma. This represented the first time a CAR T-cell therapy was indicated to treat patients with this tumor type.

“[Brexucabtagene autoleucel] has already begun to transform the outlook for many patients with relapsed or refractory mantle cell lymphoma, and we’re encouraged by the data we’ve seen in adult patients with relapsed or refractory ALL, as survival rates among these patients remain poor with the most commonly used therapeutic agents,” Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development, said in a press release. “We are working closely with the FDA to progress our application and to bring the benefits of CAR T[-cell therapy] to patients with this particularly intractable leukemia.”

ZUMA-3 has completed enrollment of a patient cohort that included patients with morphological disease in the bone marrow with 5% or more blasts, are 18 years of age or older, and have an ECOG performance status or 0 or 1. Patients with Philadelphia chromosome–positive ALL must be intolerant or have relapsed/refractory disease with 2 or more prior tyrosine kinase inhibitors and patients with prior blinatumomab (Blincyto) must have CD19 tumor expression in their bone marrow or peripheral blood. Therapy consists of a conditioning chemotherapy regimen of fludarabine and cyclophosphamide.

Results at the end of the phase 1 portion of the study were reported at the American Society of Clinical Oncology 2019 Annual Meeting. In patients with 2 months or more of follow-up (n = 41), 68% had a complete response or a complete response with incomplete hematologic (CR/CRi) recovery and 73% had undetectable minimal residual disease. For patients receiving the pivotal phase dose of 1 × 106 CAR+ T-cells/kg (n = 19), the CR/Cri rate was 84%.

Notable adverse events of therapy included grade 3 or greater cytokine release syndrome (CRS) in 29% and neurologic events in 38%. Two previously reported grade 5 events of cerebral infarction and multiorgan failure resulting from CRS were reported. Other common AEs of grade 3 or more were hypotension (38%), pyrexia (38%) and thrombocytopenia (31%). For its current approved indication, brexucabtagene autoleucel carries a black box warning for CRS and neurologic toxicities.

This application was previously granted breakthrough therapy designation by the FDA back in 2017. If approved, brexucabtagene autoleucel would be the first CAR T-cell therapy available to treat adult patients with relapsed/refractory ALL.


1. Kite submits supplemental biologics license application to U.S. Food and Drug Administration for Tecartus in adult patients with relapsed or refractory acute lymphoblastic leukemia. News release. Kite, a Gilead Company. April 1, 2021. Accessed April 5, 2021.

2. End of phase I results of ZUMA-3, a phase 1/2 study of KTE-X19, anti-CD19 chimeric antigen receptor (CAR) T cell therapy, in adult patients (pts) with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL). J Clin Oncol. 2019;37(suppl 15):7006. doi:10.1200/JCO.2019.37.15_suppl.7006

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