BeOne Medicines has announced that the US Food and Drug Administration (FDA) has approved a supplemental Biologics License Application (sBLA) for Tevimbra (tislelizumab) in combination with Ziihera (zanidatamab) and chemotherapy as a first-line treatment for adults with unresectable, locally advanced or metastatic HER2-positive (HER2+) gastric, gastroesophageal junction or esophageal adenocarcinoma (GEA).

The approval is based on results from the global Phase 3 HERIZON-GEA-01 trial, which evaluated the combination of Tevimbra, Ziihera and chemotherapy against established treatment options. Results from the study were published earlier this year in The New England Journal of Medicine.

GEA, which includes cancers of the stomach, gastroesophageal junction and esophagus, remains a significant unmet medical need in the US. More than 31,000 new stomach cancer cases are diagnosed annually, with approximately 20 percent of GEA patients having HER2-positive disease. Despite advances in treatment, outcomes for patients with advanced or metastatic HER2-positive GEA remain challenging, with fewer than 40 percent surviving beyond two years.

The HERIZON-GEA-01 results demonstrated a statistically significant improvement in overall survival (OS) with the Tevimbra-based combination. Median OS reached 26.4 months, compared with 19.2 months for the control regimen. The combination also improved Progression-Free Survival (PFS), with median PFS of 12.4 months versus 8.1 months.

The treatment benefit was observed across several patient subgroups, including those with different PD-L1 expression levels and HER2 expression levels. In patients with PD-L1-negative tumours, defined as a tumour area positivity (TAP) score below 1 percent, median OS was 29.7 months with Tevimbra, Ziihera and chemotherapy compared with 15.8 months in the control arm.

The safety profile of the combination was generally consistent with the established safety profiles of its individual components, with no new safety signals identified.

HERIZON-GEA-01 is a randomized, open-label Phase 3 study conducted jointly with Jazz Pharmaceuticals. The trial enrolled 914 patients across approximately 300 sites in more than 30 countries. Participants were randomized to receive Ziihera with chemotherapy and Tevimbra, Ziihera with chemotherapy, or trastuzumab with chemotherapy.

The trial's dual primary endpoints are progression-free survival assessed by blinded independent central review and overall survival.

Ziihera (zanidatamab) is a bispecific HER2-directed antibody designed to bind two distinct extracellular sites on the HER2 receptor. This dual binding can promote receptor internalization and trigger immune-mediated mechanisms, including complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity and antibody-dependent cellular phagocytosis.

Tevimbra (tislelizumab) is a humanized IgG4 anti-PD-1 monoclonal antibody designed to bind PD-1 with high affinity and specificity while minimizing interaction with Fc-gamma receptors on macrophages. It is the foundational asset of BeOne's solid-tumour portfolio.

The company said its global Tevimbra development programme has enrolled nearly 15,000 patients across more than 30 countries and regions, spanning 71 clinical trials, including 21 registration-enabling studies. Tevimbra is currently approved in more than 50 countries, with more than two million patients treated globally.

The latest FDA approval expands the clinical role of Tevimbra in combination-based cancer treatment and adds a new first-line option for patients with HER2-positive gastroesophageal adenocarcinoma in the United States.