FDA approves Tevimbra and Ziihera for HER2-positive gastroesophageal cancer

The FDA has approved a supplemental biologics license application for Tevimbra (tislelizumab) plus 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, BeOne Medicines announced this week. The approval is based on the results from the phase 3 HERIZON-GEA-01 trial.

Gastroesophageal adenocarcinoma (GEA) remains a significantly unmet need in the U.S., where more than 31,000 new stomach cancer cases are diagnosed each year, according to a news release by BeOne Medicines. About 20% of patients with GEA have HER2+ disease, a subtype that has historically been difficult to treat, and fewer than 40% of U.S. patients survive beyond two years, BeOne said.

HERIZON-GEA-01 is a global, randomized, open-label phase 3 trial conducted jointly with Jazz Pharmaceuticals. It compared Ziihera plus chemotherapy, with and without Tevimbra, against trastuzumab plus chemotherapy, the standard of care, as first-line treatment for adults with HER2+ GEA. The trial randomized 914 patients at about 300 sites in more than 30 countries.

Tevimbra plus Ziihera and chemotherapy showed a statistically significant improvement in overall survival, with a median of 26.4 months compared with 19.2 months for trastuzumab plus chemotherapy, and a median progression-free survival of 12.4 months compared with 8.1 months. Median duration of response was 20.7 months with the triplet regimen compared with 8.3 months for the control arm. The regimen showed consistent efficacy in patients with HER2 immunohistochemistry (IHC) scores of both 3+ and 2+.

“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,” Jaffer A. Ajani, M.D., professor of gastrointestinal medical oncology at The University of Texas MD Anderson Cancer Center, said in the news release. “With benefit observed across PD-L1 subgroups, this approval gives physicians greater freedom to select treatment regardless of PD-L1 status.”

Improvements in overall survival and progression-free survival were observed across PD-L1 subgroups. In patients with PD-L1-negative tumors, defined as tumor area positivity (TAP) below 1%, median overall survival was 29.7 months with Tevimbra and Ziihera combined and chemotherapy compared with 15.8 months for the control arm, and median progression-free survival was 18.5 months compared with 7.9 months. In patients with PD-L1-positive tumors, TAP of 1% or higher, median overall survival was 26.4 months compared with 21.2 months.

Safety findings for Tevimbra plus Ziihera and chemotherapy were generally consistent with the known safety profiles of the individual components, and no new safety signals were identified, according to BeOne. Diarrhea was the most common grade 3 or higher treatment-related adverse event, occurring in 24.5% of patients on the triplet regimen compared with 20.0% on Ziihera plus chemotherapy and 12.9% on the control arm. A mandatory anti-diarrheal prophylaxis protocol introduced during the first treatment cycle kept discontinuation due to drug-related diarrhea relatively low, at 4.1% for the triplet arm.

Mark Lanasa, M.D., Ph.D., chief medical officer of solid tumors at BeOne Medicines, called the approval an important milestone for the company. As the first approved foundational asset from BeOne's solid tumor portfolio, Tevimbra “has demonstrated the potential to address significant unmet needs across tumor types,” Lanasa said in the news release, adding that the approval reinforces BeOne's commitment to advancing new combination regimens with Tevimbra for patients facing difficult-to-treat cancers.

Aki Smith, founder and executive director of Hope for Stomach Cancer, said the approval gives patients and families reason for hope.

“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,” Smith said in the news release. “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.”