FDA Approves Tislelizumab Plus Chemotherapy for PD-L1+ Metastatic Esophageal Cancer

The US FDA has approved Tislelizumab (Tevimbra) plus platinum-based chemotherapy as a first-line treatment for adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1). The Phase 3 RATIONALE-306 trial shows that Tislelizumab plus chemotherapy significantly extended overall survival compared with chemotherapy alone.

In the PD-L1–positive (≥1) population, median OS was 16.8 months for patients treated with Tislelizumab plus chemotherapy versus 9.6 months with placebo plus chemotherapy. This represents a 34% reduction in the risk of death and an unprecedented improvement in first-line ESCC therapy.

“The approval of Tevimbra in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease,” said Dr. Nataliya Uboha, Associate Professor, University of Wisconsin, Carbone Cancer Center. “There is a critical need for effective treatments of ESCC, and Tevimbra has been shown to improve outcomes in this patient population.”

RATIONALE-306 Trial Highlights

The approval is based on results from the global, randomized, placebo-controlled, double-blind Phase 3 trial RATIONALE-306. In this study, 649 adult patients with unresectable, locally advanced, recurrent, or metastatic ESCC were randomized to receive either TEVIMBRA plus chemotherapy or placebo plus chemotherapy. The study’s primary endpoint, overall survival (OS), was met.

Key Efficacy Findings:

• Exploratory analyses indicated the OS benefit was most pronounced in the PD-L1 ≥1 subgroup (n=481).
• Median OS in this PD-L1–positive population was 16.8 months with TEVIMBRA plus chemotherapy, compared to 9.6 months with placebo plus chemotherapy (hazard ratio [HR] 0.66, 95% CI: 0.53–0.82).
• These data translate to a 34% reduction in the risk of death and represent a notable survival benefit in first-line ESCC therapy.

Safety Profile

The safety of Tevimbra in combination with chemotherapy was evaluated in the same global clinical trial, RATIONALE-306. The most frequent serious adverse reactions (≥2%) were pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common (≥20%) adverse reactions were anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.

“FDA approval of Tevimbra for the first-line treatment of advanced esophageal squamous cell carcinoma marks a significant step forward in tackling the unmet needs in this challenging disease area. We are grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible,” said Dr. Mark Lanasa, Chief Medical Officer, Solid Tumors at BeiGene.

Clinical Implications

This newly approved regimen may shift the standard of care for advanced ESCC, particularly in patients with PD-L1 ≥1. With a notable extension in overall survival—16.8 months versus 9.6 months—the TEVIMBRA plus chemotherapy combination offers a new avenue to significantly improve patient outcomes.

Tevimbra is also approved in the U.S. as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor and in combination with chemotherapy for the first-line treatment of adults with gastric and gastroesophageal junction (G/GEJ) cancers.