Brexucabtagene Autoleucel Demonstrates Overall Survival Benefit in Relapsed, Refractory B-Cell Acute Lymphoblastic Leukemia

New 3-year follow-up data from the pivotal ZUMA-3 trial in relapsed/refractory B-cell acute lymphoblastic leukemia (R/R B-ALL) shows an overall survival (OS) benefit from treatment with brexucabtagene autoleucel (Tecartus; Kite Pharma).

Brexucabtagene autoleucel is a CD19-directed genetically modified autologous T cell immunotherapy. It is indicated for adult patients with relapsed or refractory mantle cell lymphoma and adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia.

According to the new analysis, researchers found a median OS of 26 months and responses remained durable in adults with R/R B-ALL with a consistent safety profile observed since the 2-year analysis. The findings were presented during a poster session at the 5th European CAR T-Cell Meeting.

“For adult patients living with ALL, there is a need for therapeutic options that provide long-term responses,” said Bijal Shah, MD, an investigator on ZUMA-3 and medical oncologist at the Moffitt Cancer Center, in a press release. “The continued durable response and significant improvement in survival indicated by these new data can potentially establish a new standard of care for adult patients living with this aggressive form of leukemia.”

In the phase 2 treated patient cohort (N=55), the median follow-up was 38.8 months. At 36 months, the OS rate was 47.1%, with a median OS of 26 months among all treated phase 2 patients and 38.9 months in patients with complete remission (CR) or CR with incomplete hematologic recovery. Overall CR rate, CR, and subsequent allogeneic stem cell transplant rates remained unchanged since the prior data cut at 71%, 56%, and 20%, respectively.

Median relapse-free survival (RFS) censored and not censored at subsequent allogeneic stem cell transplant were both 11.6 and 11.7 months, respectively. For patients treated at the pivotal dose in both phase 1 and 2 (N=78), the median follow-up at data cutoff was 41.6 months.

Median duration of response censored and not censored at subsequent allogeneic stem cell transplant was 18.6 and 20 months, respectively. Median RFS in both groups was 11.7 months.

At data cutoff, 36% of patients were still alive with a median OS of 25.6 months in all treated patients. The proportion of pooled phase 1 and 2 patients with grade 3 or higher adverse events (AEs) that were deemed treatment-related was unchanged since the prior data cutoff, and no grade 5 AEs occurred since the prior data cutoff.

ZUMA-3 is an ongoing international multicenter, single arm, open label, registrational phase 1/2 study of brexucabtagene autoleucel in adult patients with ALL whose disease is refractory to or has relapsed following standard systemic therapy or hematopoietic stem cell transplantation. The primary endpoint is the rate of overall CR or CR with incomplete hematological recovery by central assessment. Duration of remission and RFS, OS, minimal residual disease negativity rate, and allogeneic stem cell transplantation rate were assessed as secondary endpoints.

Longer follow-up of the pivotal analysis and outcomes of a larger pooled analysis of phase 1 and 2 patients who received the pivotal dose of brexucabtagene autoleucel were reported. Most patients in the analysis were heavily pre-treated, with a median of 2 prior therapies, and 47% had received 3 or more prior therapies.

“We are encouraged by the sustained benefit that a single one-time treatment of Tecartus continues to provide for patients living with this difficult-to-treat blood cancer,” said Frank Neumann, MD, PhD, senior vice president and Kite’s global head of clinical development, in the press release. “Our hope is that these results, along with our commitment to long-term research of Tecartus, will continue to provide clarity to physicians on optimal treatment methods for these patients living with this rare disease who have suffered historically poor outcomes.”

REFERENCE

Kite’s Tecartus CAR T-cell Therapy Demonstrates Overall Survival Benefit in Three-Year Follow-up of Pivotal ZUMA-3 Trial in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia. News release. Gilead; February 9, 2023. Accessed February 24, 2023. https://www.gilead.com/news-and-press/press-room/press-releases/2023/2/kites-tecartus-car-t-cell-therapy-demonstrates-overall-survival-benefit-in-three-year-follow-up-of-pivotal-zuma-3-trial-in-relapsedrefractory-b-cel