ZUMA-2 Trial Design: Evolution of Cohorts and Brexu-Cel Dosing

In an interview with Targeted Oncology, Michael Wang, MD, The University of Texas MD Anderson Cancer Center, explains the design of the pivotal phase 2 ZUMA-2 trial (NCT02601313; NCT04880434) and how its 3 cohorts shaped the clinical and regulatory trajectory of brexucabtagene autoleucel (brexu-cel; Tecartus) in relapsed/refractory mantle cell lymphoma (R/R MCL).

Watch the first part of Dr Wang’s interview.

Cohort 1 established the foundation, enrolling 60 treated patients and demonstrating an overall response rate of 87% with a complete remission rate of 62%. Importantly, this population—largely resistant to Bruton tyrosine kinase (BTK) inhibitors and facing a life expectancy of less than 1 year—achieved a median overall survival of approximately 4 years with brexu-cel. These results supported the initial accelerated FDA approval in 2020, contingent on further data.

Cohort 2 was introduced to explore whether a lower dose could reduce toxicity. Fourteen patients received approximately 0.5 million cells compared with the 2 million used in cohort 1. However, no meaningful differences in safety or efficacy were observed, and further enrollment at the lower dose was discontinued.

To meet regulatory requirements for full approval, cohort 3 expanded the evidence base with 86 patients and a key design change: unlike cohorts 1 and 2, prior BTK inhibitor exposure was not required. The iterative cohort design of ZUMA-2 played a critical role in refining dosing, broadening eligibility, and ultimately supporting full FDA approval of brexu-cel in early April 2026.

Read the full interview here.