sBLA Filed With FDA for Brexucabtagene Autoleucel in Adult ALL

A supplemental biologics license application for brexucabtagene autoleucel for the treatment of adult patients with relapsed or refractory B-cell precursors acute lymphoblastic leukemia.

A supplemental biologics license application (sBLA) for brexucabtagene autoleucel (Tecartus) for the treatment of adult patients with relapsed or refractory B-cell precursors acute lymphoblastic leukemia (ALL), according to a press release by Kite, a subsidiary of Gilead.1

Brexucabtagene autoleucel is an autologous, anti-CD19 chimeric antigen receptor (CAR) T-cell therapy that includes T-cell enrichment. For B-cell malignancies with circulating lymphoblasts, this step is necessary. The application seeking FDA approval issuppored by results from the phase 1/2 ZUMA-3 (NCT02614066).1

ZUMA-3 enrolled a total of 125 participants. The study is ongoing and assess patients for the primary outcomes of the percentage of participants experiencing dose-limiting toxicities (DLTs) and over all complete remission (CR) rate. Secondary outcomes included duration of remission, minimum residual disease negative remission rate, allogenic stem cell transplant rate, overall survival, and relapse-free survival.

During the single arm study, patients receive a conditioning chemotherapy regimen of fludarabine and brexucabtagene autoleucel. This is then followed by a single infusion of CAR transduced autologous T cells administered intravenously at a target dose of 2 x 106 anti-CD19 CAR+ T cells/kg or 1 x 106 anti-CD19 CAR+ T cells/kg.

In order to participate, patients must be 18 years old or older, have relapsed or refractory B-precursor ALL. Additionally, patients must have morphological disease in the bone marrow. Patients with a diagnosis of Burkitt’s leukemia/lymphoma or a history of malignancy other than non-melanoma skin cancer or carcinoma in situ are not eligible to participate.

At the interim analysis, 45 patients had been dosed with the combination. Th median age was 46 years old and 66% have had 3 or more prior lines of treatment. There were no reported DLTs in the DLT-evaluated patients. The most common grade 3 or higher adverse event (AE) was hypotension (38%). The median event-free survival was 15 months. 2

“Tecartus 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,” said Frank Neumann, MD, PhD, global head of clinical development, Kite, in a press release. “We are working closely with the FDA to progress our application and to bring the benefits of CAR T to patients with this particularly intractable leukemia.”

Currently, brexucabtagene autoleucel is the only CAR T-cell therapy to receive an accelerated approval from the FDA or the treatment of relapsed or refractory mantle cell lymphoma, which was granted in July 2020. In 2017, the agent was granted breakthrough therapy designation. If it is approved brexucabtagene autoleucel will be the only CAR T-cell therapy for adult relapsed/refractory ALL. In addition to adult ALL, the agent is being investigated in pediatric ALL and chronic lymphocytic leukemia.1

REFERENCE:
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. April 1, 2021. Accessed April 2, 2021. https://bit.ly/3rTGiHn
2. Shah, B., Bishop, M., Oluwole, O.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). Jour. of Clin. Onc. 37, no. 15_suppl (May 20, 2019) 7006-7006. DOI: 10.1200/JCO.2019.37.15_suppl.7006