Yescarta Meets Endpoints in Second-line DLBCL; Supplemental BLA Planned

Kite plans to submit a supplemental BLA based on these findings.

Kite, a Gilead Company, has announced positive top-line results from the phase 3 ZUMA-7 trial of CAR T-cell therapy Yescarta (axicabtagene ciloleucel) in second-line relapsed or refractory large B-cell lymphoma. The trial met the primary endpoint of event-free survival, with a 60% reduction in the risk of disease progression, introduction of new lymphoma therapy or death over current standard of care, which is chemotherapy plus stem cell transplant.

“The top-line results of the randomized ZUMA-7 trial paint the picture of a potential paradigm shift in the treatment of large B-cell lymphoma,” Frederick L. Locke, MD, lead principal investigator and co-leader of the Immuno-Oncology Program at Moffitt Cancer Center in Tampa, said in a statement. “The outcomes for patients relapsing after frontline chemotherapy in this study are dramatically improved with rapid referral (to a CAR T center) and a single infusion of axicabtagene ciloleucel as compared with chemotherapy and consolidative autologous transplant, the longstanding second-line standard of care.”

About 40% of patients with LBCL will need second-line treatment because their cancer will either relapse or become refractory to treatment.

Safety results from the study were consistent with or lower than the known safety profile of Yescarta for the treatment of LBCL in the third-line setting. Six percent of patients experienced cytokine release syndrome (CRS) Grade 3 or higher, with a median onset of three days, and 21% experienced neurological events Grade 3 or higher. No new safety concerns were identified in this second-line setting.

ZUMA-7 was initiated in 2017 and enrolled 359 patients in 77 centers around the world. The results represent the longest follow-up time of any study in this setting with two years median follow-up. Patients enrolled in the study ranged in age from 22 to 81, with 30% of the patients 65 or older.

Kite plans to initiate discussions with the FDA, the European Medicines Agency, and health authorities regarding submission of a supplemental Biologics License Application later this year.

Yescarta is a CD19-directed genetically modified autologous T cell immunotherapy already available to treat adult patients with relapsed or refractory large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma and adult patients with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy.