FDA Approves BeiGene’s Tevimbra for Unresectable or Metastatic HER2-Negative Gastric or Gastroesophageal Junction Adenocarcinoma

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The FDA has approved BeiGene’s Tevimbra (tislelizumab-jsgr) in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of unresectable or metastatic HER2-negative gastric or gastroesophageal junction (G/GEJ) adenocarcinoma in adults with PD-L1 expression. The approval, which was the second for Tevimbra in 2024, is supported by results from the RATIONALE-305 Phase III trial, which demonstrated a significant overall survival (OS) benefit.¹

“[The] FDA approval of Tevimbra for the treatment of gastric or gastroesophageal junction cancers in PD-L1 positive adult patients marks a significant step forward in our mission to deliver transformative therapies to patients with cancer,” said Mark Lanasa, MD., PhD, chief medical officer, solid tumors, BeiGene, in a press release. “This is the second US approval for Tevimbra this year, underscoring its potential to address critical needs in oncology. We remain deeply grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible—and we look forward to building on this momentum in 2025.”

The randomized, double-blind, placebo-controlled, global RATIONALE 305 trial compared the efficacy and safety of Tevimbra combined with platinum and fluoropyrimidine chemotherapy vs. placebo combined with platinum and fluoropyrimidine chemotherapy. As part of the trial, 997 patients from 13 countries were randomly assigned in a 1:1 ratio to receive either Tevimbra or placebo in combination with chemotherapy. The primary endpoint of the trial was OS, with prespecified hierarchy testing for the PD-L1 high population followed by the intent-to-treat (ITT) population. Secondary endpoints included progression-free survival, overall response rate, duration of response, and safety. Topline results from the trial were first presented at the 2023 ASCO Gastrointestinal Cancers Symposium.²

“At the recent ASCO GI meeting, we presented results from an interim analysis demonstrating a statistically significant and clinically meaningful improvement in overall survival in the high PD-L1 expression group in RATIONALE 305 and we are pleased that the final analysis demonstrated a significant survival benefit and consistent safety profile in the entire study population,” said Lanasa, in the 2023 press release. “Gastric cancer is the fifth most common cancer globally, and the prognosis for patients with advanced or metastatic conditions remains inadequate; these data support tislelizumab combined with chemotherapy as a potential first-line treatment option for patients with locally advanced, unresectable or metastatic gastric or gastroesophageal junction cancer.”

Data pooled from 1,972 patients in RATIONALE-305, BGB-A317-303, and five open-label, single-arm studies found that the most common adverse events associated with the treatment included neutropenia; thrombocytopenia; anemia; fatigue; hypokalemia; hyponatremia; pneumonia; decreased appetite; rash; lymphopenia; alanine aminotransferase increased; aspartate aminotransferase increased; diarrhea; pneumonitis; and hepatitis.

According to BeiGene, gastric cancer is the fifth most common cancer worldwide and the fifth highest leading cause of cancer deaths, with approximately one million new cases diagnosed in 2022. Additionally, 660,000 people died in 2022 as a result of gastric cancer globally. In the United States, there were approximately 27,000 patients diagnosed with gastric cancer and 11,000 deaths from the disease last year. Currently, the five-year survival rate for gastric cancer in the United States is 36%.¹

According to the American Cancer Society, gastric cancer accounts for 1.5% of all cancers in the United States. It is most common in people over 65 years of age, with a median diagnosis age of 68 years.³

Tevimbra is currently approved for treating metastatic esophageal squamous cell carcinoma (ESCC) and has a Biologics License Application under review for first-line ESCC treatment.¹

References

1. TEVIMBRA Approved in U.S. for First-line Treatment of Gastric and Gastroesophageal Junction Cancers in Combination with Chemotherapy. BeiGene. December 27, 2024. Accessed January 2, 2025. https://ir.beigene.com/news/tevimbra-approved-in-u-s-for-first-line-treatment-of-gastric-and-gastroesophageal-junction-cancers-in-combination/cedb475b-fcfe-47a4-8afe-8a501d9cf849/

2. BeiGene Announces Positive Phase 3 Tislelizumab Trial in Advanced Gastric or Gastroesophageal Junction Adenocarcinoma. BeiGene. April 20, 2023. Accessed January 2, 2025. https://ir.beigene.com/news/beigene-announces-positive-phase-3-tislelizumab-trial-in-advanced-gastric-or-gastroesophageal-junction-adenocarcinoma/dc7ae8df-dbbb-4de2-834f-0f74feaaa519/

3. Key Statistics About Stomach Cancer. American Cancer Society. Accessed January 2, 2025. https://www.cancer.org/cancer/types/stomach-cancer/about/key-statistics.html