FDA Approves Tislelizumab-jsgr as First-Line Therapy for HER2– Gastric Cancers

The FDA approved tislelizumab-jsgr (Tevimbra) in combination with platinum and fluoropyrimidine-based chemotherapy as a first-line treatment for unresectable or metastatic HER2-negative (HER–) gastric or gastroesophageal junction adenocarcinoma (G/GEJ) in adults whose tumors express PD-L1.1

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The approval follows its initial approval in March 2024, when tislelizumab was approved as a monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) after prior systemic chemotherapy that did not include a PD-L1 inhibitor.2 The manufacturer Beigene has also submitted a biologics license application for the use of tislelizumab as a first-line treatment of adult patients with locally advanced unresectable or metastatic ESCC.

“This is the second U.S. 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.”

FDA based its decision on the results of the global, randomized, double-blind, placebo-controlled phase 3 RATIONALE-305 (NCT03777657) study, evaluating the efficacy and safety of TEVIMBRA (tislelizumab) in combination with chemotherapy as a first-line treatment for adults with advanced, unresectable, or metastatic G/GEJ cancers.1

The trial enrolled 997 patients who were randomized to receive either tislelizumab with investigator-selected chemotherapy or placebo with chemotherapy. The study met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in overall survival (OS).

Patients treated with tislelizumab and chemotherapy achieved a median OS of 15.0 months compared to 12.9 months for the placebo group, representing a 20% reduction in the risk of death (HR, 0.80; 95% CI, 0.70-0.92; P = .0011). Safety data pooled from 1,972 patients across multiple studies revealed that common grade 3 or 4 adverse reactions when tislelizumab was combined with chemotherapy included neutropenia, thrombocytopenia, anemia, fatigue, rash, pneumonia, pneumonitis, hypokalemia, hyponatremia, decreased appetite, hepatitis, and elevated liver enzymes. The findings highlighted tislelizumab’s potential as a valuable first-line treatment option, providing significant survival benefits for patients with advanced G/GEJ cancers while maintaining a manageable safety profile.

Additionally, the National Comprehensive Cancer Network updated its guidelines for hepatocellular carcinoma (HCC) to add tislelizumab as a category 1 other recommended regimen.3

Gastric cancer is the fifth most common cancer globally and ranks fifth in cancer-related deaths, with nearly 1 million new cases and 660,000 deaths reported in 2022.1 In the US, approximately 27,000 new cases and 11,000 deaths were estimated in 2024, with a 5-year survival rate of 36%. GEJ cancer, which occurs where the esophagus meets the stomach beneath the diaphragm, represents a distinct and challenging subset of these cancers.

According to a study published in Annals of Surgery, patients with GEJ cancer have worse disease-specific survival and a higher recurrence rate than those with gastric cancer, with hematogenous recurrence being more common in GEJ cancer (60.1% vs 31.4%) and peritoneal recurrence more frequent in gastric cancer (52.9% vs. 12.5%).4 Together, esophageal and gastric cancers account for 1.6 million new cases and 1.3 million deaths annually. GEJ cancer incidence has risen significantly, with a 2.5-fold increase in 2 decades, and non-cardia gastric adenocarcinoma is increasing in younger individuals. Surgery remains central to treatment, but perioperative therapies play a key role in advanced cases.

References

1. Tevimbra approved in U.S. for first-line treatment of gastric and gastroesophageal junction cancers in combination with chemotherapy. Press release. Beigene; December 27, 2024. Accessed January 2, 2025. https://www.businesswire.com/news/home/20241227403101/en/TEVIMBRA-Approved-in-U.S.-for-First-line-Treatment-of-Gastric-and-Gastroesophageal-Junction-Cancers-in-Combination-with-Chemotherapy

2. Rosa K. FDA approves tislelizumab for advanced or metastatic ESCC after chemotherapy. AJMC.com. March 15, 2024. Accessed January 2, 2025. https://www.ajmc.com/view/fda-approves-tislelizumab-for-advanced-or-metastatic-escc-after-chemotherapy

3. Hollasch M. Tislelizumab pushes HCC field forward with 2024 NCCN Guideline category 1 recommendation. AJMC.com. December 1, 2024. Accessed January 2, 2025. https://www.ajmc.com/view/tislelizumab-pushes-hcc-field-forward-with-2024-nccn-guideline-category-1-recommendation

4. Nakauchi M, Vos EL, Carr RA, et al. Distinct differences in gastroesophageal junction and gastric adenocarcinoma in 2194 patients. Ann Surg. 2021;277(4):629–636. doi: 10.1097/SLA.0000000000005320