BeiGene announced today that the U.S. Food and Drug Administration (FDA) has approved Tevimbra (tislelizumab-jsgr), in combination with platinum-containing chemotherapy, for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).
This approval represents a significant advancement for patients with this aggressive form of cancer, which has historically had limited treatment options and poor survival outcomes.
Groundbreaking Clinical Results
The FDA approval is based on results from the global Phase 3 RATIONALE-306 trial (NCT03783442), which evaluated the efficacy and safety of Tevimbra in combination with platinum-containing chemotherapy as a first-line treatment in 649 adult patients with unresectable, locally advanced recurrent or metastatic ESCC.
The study met its primary endpoint, demonstrating a statistically significant improvement in overall survival (OS) for patients receiving Tevimbra plus chemotherapy compared to placebo plus chemotherapy. Exploratory analyses indicated that the improvement was primarily driven by results in patients whose tumors expressed PD-L1.
In the PD-L1 positive (≥1) population (n=481), the median overall survival was 16.8 months for patients treated with Tevimbra plus chemotherapy compared to 9.6 months for those receiving placebo plus chemotherapy (HR: 0.66, [95% CI: 0.53, 0.82]). This represents a 34% reduction in the risk of death – an unprecedented improvement in overall survival for first-line ESCC patients.
"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 at the University of Wisconsin's 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."
Safety Profile
The safety of Tevimbra in combination with chemotherapy was evaluated in the same RATIONALE-306 trial. The most frequent serious adverse reactions (≥2%) were pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common (≥20%) adverse reactions included anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.
Addressing a Significant Unmet Need
Esophageal cancer is the sixth most common cause of cancer-related deaths globally, with ESCC accounting for nearly 90% of esophageal cancers worldwide. An estimated 957,000 new esophageal cancer cases are projected by 2040, representing an increase of nearly 60% from 2020.
Esophageal cancer is a rapidly fatal disease, with more than two-thirds of patients having advanced or metastatic disease at the time of diagnosis. The five-year survival rate for those with distant metastases is less than 6%, underscoring the urgent need for more effective treatment options.
"Today's approval, our third from the FDA in less than a year, reflects our dedication to advancing innovative therapies and addressing critical needs in cancer care," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "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."
About Tevimbra
Tevimbra is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping the body's immune cells detect and fight tumors.
The drug is the foundational asset of BeiGene's solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global Tevimbra clinical development program includes almost 14,000 patients enrolled to date in 34 countries and regions across 66 trials, including 20 registration-enabling studies.
Tevimbra is now approved in more than 42 countries, and more than 1.3 million patients have been treated globally. In the United States, Tevimbra is also approved as monotherapy for the treatment of adult patients with unresectable or metastatic ESCC 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.
Corporate Evolution
BeiGene recently announced its intent to change its name to BeOne Medicines Ltd., reaffirming its commitment to developing innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.
The company's expanding portfolio and global reach highlight its growing influence in the oncology space, with Tevimbra serving as a cornerstone of its development strategy.
Looking Forward
With this latest approval, Tevimbra continues to demonstrate its potential as an important treatment option across multiple gastrointestinal cancers. The significant survival benefit observed in the RATIONALE-306 trial provides new hope for patients with advanced ESCC, a population with historically limited treatment options.
As BeiGene continues to expand its global presence and advance its pipeline, the company remains focused on addressing critical unmet needs in oncology and improving outcomes for cancer patients worldwide.
