Kite Announces Yescarta® CAR T-cell Therapy Improved Event-Free Survival by 60% Over Chemotherapy Plus Stem Cell Transplant in Second-Line Relapsed or Refractory Large B-cell Lymphoma
Kite, a Gilead Company (Nasdaq: GILD), today announced top-line results from the primary analysis of ZUMA-7, a randomized Phase 3 global, multicenter study showing superiority of Yescarta® (axicabtagene ciloleucel) compared to standard of care (SOC) in second-line relapsed or refractory large B-cell lymphoma (LBCL). With a median follow-up of two years, the study met the primary endpoint of event-free survival (EFS; hazard ratio 0.398, p <0.0001). The study also met the key secondary endpoint of objective response rate (ORR). The interim analysis of overall survival (OS) showed a trend favoring Yescarta; however, the data are immature at this time, and further analyses are planned for the future.
Overall survival measures deaths over time from any cause. Event-free survival is defined as time from randomization to disease progression, commencement of new lymphoma therapy, or death from any cause. ZUMA-7 was conducted under a Special Protocol Agreement (SPA) with the U.S. Food and Drug Administration (FDA) whereby the trial design, clinical endpoints and statistical analysis were agreed in advance with the Agency.
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.
“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,” said Frederick L. Locke, MD, ZUMA-7 Lead Principal Investigator and Co-Leader of the Immuno-Oncology Program at Moffitt Cancer Center, Tampa, Florida. “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 to chemotherapy and consolidative autologous transplant, the longstanding second-line standard of care.”
ZUMA-7 evaluated an one-time infusion of the CAR T-cell therapy Yescarta compared to SOC in adult patients with relapsed or refractory LBCL. Standard of care for relapsed or refractory LBCL is a two-step process: immunochemotherapy is reintroduced, and if the patient responds and can tolerate further treatment, they move on to high-dose chemotherapy plus stem cell transplant.
“Yescarta has been instrumental in transforming outcomes for patients with third-line LBCL. Our goal has always been to bring the benefit of CAR T-cell therapy to more patients, earlier in their treatment, where the potential for benefit may be even greater,” said Christi Shaw, Chief Executive Officer of Kite. “As the leader in cell therapy, Kite is honored to deliver this landmark study and would like to thank the patients, families, physicians and care teams around the world that made this possible.”
ZUMA-7 was initiated in 2017 and enrolled 359 patients in 77 centers around the world. Results released today 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.
“Over 40 years ago, we learned the important role T-cells play in fighting cancer, and 20 years ago autologous stem cell transplant became an option to treat lymphoma. Today’s results show us the potential power of cell therapy for patients with lymphoma when used earlier, and instead of standard treatment options,” said Frank Neumann, MD, PhD, Kite’s Global Head of Clinical Development.
Detailed results from ZUMA-7 will be submitted for presentation at a future medical congress, and Kite plans to initiate discussions with the U.S. Food and Drug Administration, European Medicines Agency and other global health authorities regarding submission of a supplemental Biologics License Application later this year to expand the currently approved indications for Yescarta. See About Yescarta section for current Yescarta approved indications. Yescarta has not been approved by any regulatory agency for the treatment of patients in the second-line setting similar to those in ZUMA-7.
About 40% of patients with LBCL will need second-line treatment, as their cancer will either relapse (return) or become refractory (not respond) to treatment.