-BeOne Medicines Ltd. (Nasdaq: ONC; HKEX: 06160; SSE: 688235), a global oncology company, today announced that the U.S. Food and Drug Administration (FDA) has approved the supplemental Biologics License Application (sBLA) for TEVIMBRA^® (tislelizumab) in combination with ZIIHERA^® (zanidatamab) and chemotherapy for the first-line treatment of adult patients with unresectable locally advanced or metastatic HER2-positive (HER2+) gastric, gastroesophageal junction, or esophageal adenocarcinoma (GEA). The approval is supported by results from the Phase 3 HERIZON-GEA-01 trial, which were published in The New England Journal of Medicine earlier this year.

GEA, which includes adenocarcinomas of the stomach, gastroesophageal junction and esophagus, remains an area of substantial unmet need in the United States, with more than 31,000 new stomach cancer cases diagnosed each year.¹ Approximately 20% of patients with GEA have HER2+ disease, a subtype that has historically been difficult to treat.^2,3,4

Despite recent advances, long-term outcomes for patients with advanced or metastatic HER2+ GEA remain challenging and the need for more effective first-line options is urgent. In the U.S., fewer than 40% of patients survive beyond two years. These outcomes highlight the need for additional treatment options that may help extend survival for patients facing this disease.

Jaffer A. Ajani, M.D., Professor of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, said:

“For patients with advanced HER2-positive gastroesophageal adenocarcinoma, first-line treatment represents a critical opportunity to make the greatest possible impact and change the course of disease at the start of care, making it especially important to provide the most effective treatment options and combinations upfront to give patients the best possible chance for improved outcomes. The median overall survival of more than two years observed with this regimen demonstrates meaningful progress in a setting where outcomes have historically been challenging to improve. With benefit observed across PD-L1 subgroups, this approval gives physicians greater freedom to select treatment regardless of PD-L1 status.”

Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeOne Medicines, said:

“Today’s approval is an important milestone for BeOne as we continue to expand the impact of TEVIMBRA for patients living with cancer. As the first approved foundational asset to emerge from our solid tumor portfolio, TEVIMBRA has demonstrated the potential to address significant unmet needs across tumor types, and today’s approval further reinforces our commitment to advancing innovative, practice changing combination regimens with TEVIMBRA for patients facing difficult-to-treat cancers. We are proud to bring this new first-line treatment option to physicians and patients with HER2-positive gastroesophageal adenocarcinoma in the United States.”

Aki Smith, Founder & Executive Director, Hope for Stomach Cancer, said:

“For people living with HER2-positive gastroesophageal cancer and their families, the possibility of more time can mean everything - more moments with loved ones, more milestones, and more confidence that progress is being made in a disease where additional options are urgently needed. As a caregiver to my father, who faced HER2-positive gastroesophageal cancer, I know personally the fear and urgency families feel when treatment begins and how much it means to have more options available from the very start. We welcome the availability of this new regimen and remain committed to helping patients and caregivers understand their treatment options and access the support they need throughout their journey.”

Approval supported by Phase 3 HERIZON-GEA-01 results

The approval is based on data from HERIZON-GEA-01, the global Phase 3 clinical trial evaluating ZIIHERA plus chemotherapy, with and without TEVIMBRA, compared with trastuzumab plus chemotherapy as first-line treatment for advanced or metastatic HER2+ GEA.

Key findings from the trial include:

• Overall survival (OS): TEVIMBRA plus ZIIHERA and chemotherapy demonstrated a statistically significant improvement in OS, with median OS of 26.4 months compared with 19.2 months in the control arm.
• Progression-free survival (PFS): TEVIMBRA plus ZIIHERA and chemotherapy demonstrated a statistically significant and clinically meaningful improvement in PFS, with a median PFS of 12.4 months compared with 8.1 months in the control arm.
• Consistent benefit regardless of PD-L1 status: improvements in OS and PFS were observed across patient subgroups, including patients with PD-L1-negative tumors (TAP <1%), where median OS was 29.7 months with TEVIMBRA plus ZIIHERA and chemotherapy compared with 15.8 months in the control arm.
• Consistent efficacy across HER2 expression levels: TEVIMBRA + ZIIHERA and chemotherapy showed benefit in both HER2 IHC (immunohistochemistry) 3+ and HER2 IHC 2+ populations.
• Safety: treatment with TEVIMBRA plus ZIIHERA and chemotherapy was generally consistent with the known safety profiles of the components of the regimen, and no new safety signals were identified.