Results from a new phase III study showed that in patients with HER2-positive metastatic gastroesophageal adenocarcinoma, the combination of the dual HER2-targeted bispecific antibody zanidatamab and chemotherapy, with or without the PD-1 inhibitor tislelizumab, extended progression-free survival. The research will be presented by Elimova et al at the 2026 ASCO Gastrointestinal Cancers Symposium, January 8–10 in San Francisco (Abstract LBA285).
HERIZON-GEA-01
HERIZON-GEA-01 included 914 patients with metastatic or locally advanced unresectable gastroesophageal adenocarcinoma who had not yet received treatment for their cancer.
The participants were randomly assigned to one of three treatment groups: zanidatamab and chemotherapy with tislelizumab, zanidatamab and chemotherapy; or trastuzumab and chemotherapy, the standard of care at the time the study was designed
Key Findings
After a median follow-up of 26 months, the median progression-free survival was 12.4 months in patients who received zanidatamab and chemotherapy with or without tislelizumab vs 8.1 months in patients who received trastuzumab.
Overall, zanidatamab reduced the risk of cancer progression or death by about 35%.
After 18 months of treatment, the cancer had not grown or spread in about 44% of patients who received zanidatamab, tislelizumab, and chemotherapy; it had not grown or spread in 38% of patients who received zanidatamab and chemotherapy; and it had not grown or spread in about 21% of those in the trastuzumab group.
The median overall survival was 26.4 months in patients who received the combination of zanidatamab, tislelizumab, and chemotherapy. The overall survival data was not statistically significant at the time of this analysis for the patients who received zanidatamab with chemotherapy, but researchers observed a trend in overall survival benefit for this group, too.
About 72% of patients in the zanidatamab, tislelizumab, and chemotherapy group experienced a grade 3 or higher adverse event compared to about 59% in the other two groups.
About 12% of patients in the zanidatamab, tislelizumab, and chemotherapy group and 8.5% of patients in the zanidatamab with chemotherapy group stopped treatment compared to 2.3% of patients in the trastuzumab group.
The most common serious side effects in the zanidatamab groups were diarrhea, hypokalemia, and anemia. In the trastuzumab group, diarrhea, anemia, decreased white blood cell counts, and decreased platelet counts were most common. Since diarrhea is a known side effect of zanidatamab, patients in these groups received a drug to help lessen or prevent it.
“Despite the adoption of newer therapies in recent years, outcomes for patients with metastatic gastroesophageal adenocarcinoma have remained modest. This is the first phase III trial to demonstrate a benefit for a novel HER2-targeted therapy compared to trastuzumab as part of a combination regimen in HER2-positive first-line treatment for these patients,” said lead study author Elena Elimova, MD, of Princess Margaret Cancer Centre in Toronto.
Next Steps
The researchers have an additional planned overall survival interim analysis in mid-2026 for zanidatamab plus chemotherapy. Zanidatamab is also being investigated across many different types of treatments in multiple HER2-expressing solid tumors.
ASCO Perspective
“Despite recent advances, many patients with metastatic gastroesophageal adenocarcinoma still experience disease progression within a year of treatment. These are practice-changing results that offer a new treatment option for patients with HER2-positive upper GI cancers,” said Rachna Shroff, MD, MS, FASCO, an ASCO Expert in gastrointestinal cancers and Associate Director of Clinical Investigations and co-leader of the Gastrointestinal Clinical Research Team at the University of Arizona Cancer Center.
Disclosure: This study was sponsored by Jazz Pharmaceuticals conducted jointly with BeOne Medicines. For full disclosures of the study authors, visit coi.asco.org.
