-- First Treatment in Nearly 30 Years to Show Statistically Significant OS, With a Median Follow-Up of 47.2 Months, for Initial Treatment of R/R LBCL Versus Historical SOC in the Curative Setting --

-- Yescarta Results in a 27.4% Reduction in Risk of Death, Corresponding to a 38% Relative Improvement in OS, Despite 57% of Patients Subsequently Receiving Cell Therapy Off Protocol --

-- Data Highlighted as Late-Breaking News at ASCO 2023 and Simultaneously Published in the New England Journal of Medicine --

SANTA MONICA, Calif.--(BUSINESS WIRE)-- Kite, a Gilead Company (Nasdaq: GILD), today announces detailed results from the overall survival (OS) analysis of the landmark Phase 3 ZUMA-7 study of Yescarta® (axicabtagene ciloleucel [axi-cel]) CAR T-cell therapy compared with historical standard of care (SOC) as initial treatment in the curative setting for patients with relapsed or refractory large B-cell lymphoma (R/R LBCL). Yescarta is the first treatment in nearly 30 years to demonstrate a significant improvement in survival in this patient population. The late-breaking data are being presented orally at the 2023 American Society of Clinical Oncology Annual Meeting (Abstract #LBA107) and published simultaneously in the New England Journal of Medicine.

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With a median follow-up of 4 years (47.2 months), a one-time treatment with Yescarta demonstrated significantly longer overall survival (hazard ratio [HR] 0.726; 95% CI: 0.540-0.977, stratified one-sided log rank p-value = 0.0168) compared to SOC with a 27.4% reduction in the risk of death, which corresponds to a 38% relative improvement in overall survival, for patients with R/R LBCL within 12 months completion of first-line therapy.

SOC therapy for this patient population has historically been a multi-step process expected to end with stem-cell transplant. The process starts with chemoimmunotherapy, and if a patient responds and can tolerate further treatment, they move on to high-dose chemotherapy (HDT), followed by stem cell transplant (ASCT). It is notable that despite this process being the historical SOC, less than 40% of patients were able to make it through to complete their stem cell transplant compared with 94% of patients in the ZUMA-7 study who received Yescarta CAR T-cell therapy.

“As the first treatment in nearly three decades to significantly improve survival for patients with relapsed/refractory large B-cell lymphoma, axi-cel can potentially change the standard of care for these patients who previously had very limited options for successful curative therapy,” said Jason Westin, MD, MS, FACP, ZUMA-7 Principal Investigator, Director, Lymphoma Clinical Research, and Associate Professor, Department of Lymphoma/Myeloma at The University of Texas MD Anderson Cancer Center. “The totality of the ZUMA-7 data provides a compelling case for axi-cel to be used as soon as patients with large B-cell lymphoma do not respond to or relapse from first-line treatment.”

The primary OS analysis, conducted per protocol five years after the first subject was randomized, demonstrated superior OS with Yescarta over the SOC arm, despite more than half (57%) of patients in the SOC arm subsequently receiving cellular immunotherapy off protocol; of these, 77% of patients received Yescarta. Median OS was longer with Yescarta versus SOC (not reached versus 31.1 months, respectively) and 48-month OS estimates were higher with Yescarta (54.6% versus 46.0%, respectively). Yescarta’s OS benefit versus SOC was also similar across key patient subgroups, including patients with high-risk features, such as those with primary refractory disease, high-grade B-cell lymphoma (including double-hit lymphomas) and aged 65 and above. Progression-free survival (PFS) by investigator review confirmed the benefit of Yescarta over SOC (HR 0.506; 95% CI: 0.383-0.669), with 48-month PFS estimates of 41.8% with Yescarta versus 24.4% with SOC.

Yescarta’s safety profile remains consistent with prior studies, and no new treatment-related deaths occurred since the primary EFS analysis. The primary EFS analysis showed that Grade 3 or higher adverse events (AEs) occurred in 91% of patients treated with axi-cel compared with 83% of those treated with SOC. The most common grade 3 or higher AEs were neutropenia (69% vs 41%, respectively), anemia (30% vs 39%), and leukopenia (29% vs 22%).

“Overall survival is the gold standard in cancer treatment and confirms Yescarta’s place as a treatment of curative intent for patients with relapsed/refractory large B-cell lymphoma,” said Frank Neumann, MD, PhD, SVP, Kite’s Global Head of Clinical Development. “Kite shares this momentous achievement with all of the patients and researchers who participated in the ZUMA-7 study since the first patient was randomized five years ago.”

About ZUMA-7 Study

Based on the results of primary efficacy endpoint of event-free survival (EFS) in the pivotal ZUMA-7 trial, the U.S. Food & Drug Administration approved Yescarta as initial treatment of R/R LBCL in April 2022. The EU granted approval in October 2022, followed by approvals in several other countries such as: Australia, Canada, Great Britain, Israel, Japan and Switzerland.

ZUMA-7 is a randomized, open-label, global, multicenter, Phase 3 study evaluating the safety and efficacy of Yescarta versus SOC for second-line therapy in adult patients with relapsed or refractory LBCL within 12 months of first-line therapy. The SOC for initial treatment of R/R LBCL has been a multi-step process involving platinum-based salvage combination chemotherapy regimen, and for responders, high-dose therapy (HDT) and autologous stem cell transplant (ASCT). In the study, 359 patients in 77 centers around the world were randomized (1:1) to receive a single infusion of Yescarta or SOC second-line treatment. The primary endpoint was EFS as determined by blinded central review and defined as the time from randomization to the earliest date of disease progression per Lugano Classification, commencement of new lymphoma therapy, or death from any cause. Key secondary endpoints include objective response rate (ORR) per blinded central review and overall survival (OS). Additional secondary endpoints included patient reported outcomes (PROs) and safety. Per hierarchical testing of primary and key secondary endpoints and group sequential testing of OS, an interim analysis of OS occurred at the time of the primary EFS.

Yescarta demonstrated a 2.5-fold increase in patients who were alive at two years and did not experience cancer progression or require additional cancer treatment (40.5% vs. 16.3%) and a four-fold greater median EFS (8.3 mo. vs. 2.0 mo.) compared to SOC (hazard ratio 0.398; 95% CI: 0.308-0.514, P