A new treatment zanidatamab (Ziihera), given with chemotherapy and tislelizumab (Tevimbra), showed meaningful improvements in survival for people with HER2-positive metastatic gastroesophageal adenocarcinoma (GEA)—a type of stomach or esophageal cancer that has spread—compared with the current standard therapy using trastuzumab (Herceptin).
Promising results from the HERIZON-GEA-01 trial
According to results from the phase 3 HERIZON-GEA-01 clinical trial, presented at the 2026 Gastrointestinal Cancers Symposium, patients who received zanidatamab with chemotherapy (with or without tislelizumab) lived longer without their cancer worsening and also lived longer overall than those treated with trastuzumab.
- Progression-free survival (PFS): Median of 12.4 months with zanidatamab-based treatment vs 8.1 months with trastuzumab.
- Overall survival (OS): Median of 26.4 months vs 19.2 months, respectively.
These results mark the first time a phase 3 study in this disease has shown a median survival beyond 1 year without disease progression and 2 years overall.
How the study was designed
The HERIZON-GEA-01 trial enrolled 914 patients with previously untreated HER2-positive advanced or metastatic stomach or gastroesophageal junction cancer. Participants were randomly assigned to one of three treatment groups:
- Trastuzumab + chemotherapy (standard treatment)
- Zanidatamab + tislelizumab + chemotherapy
- Zanidatamab + chemotherapy
Treatment continued until the cancer worsened, side effects became too difficult, or the patient chose to stop therapy.
A closer look at side effects
The combination of zanidatamab, chemotherapy, and tislelizumab showed an expected and manageable safety profile. Common side effects included diarrhea, nausea, vomiting, and low blood counts, most of which improved with supportive care.
Serious treatment-related side effects occurred in some patients, but no new or unexpected safety concerns were reported.
What’s next for zanidatamab
The HERIZON-GEA-01 trial is continuing to monitor long-term survival. Additional studies are also testing zanidatamab in other types of HER2-positive cancers, including biliary tract and breast cancers.
If final results confirm the benefits seen so far, zanidatamab—alone or with tislelizumab—could soon become a new first-line standard of care for patients with HER2-positive advanced gastroesophageal cancer.
Zanidatamab (Ziihera) currently has a single formal FDA indication in the United States:
- Zanidatamab is approved with accelerated approval for adults with previously treated, unresectable or metastatic HER2‑positive (IHC 3+) biliary tract cancer (including cholangiocarcinoma and gallbladder cancer), confirmed by an FDA‑approved test.
- This approval is based on objective response rate and duration of response from the HERIZON‑BTC‑01 trial; continued approval may be contingent on confirmatory benefit in an ongoing phase 3 study (HERIZON‑BTC‑302).
Reference
Elimova E, Rha SY, Shitara K, et al. Zanidatamab + chemotherapy (CT) ± tislelizumab for first-line (1L) HER2-positive (HER2+) locally advanced, unresectable, or metastatic gastroesophageal adenocarcinoma (mGEA): primary analysis from HERIZON-GEA-01. J Clin Oncol. 2026, 44(suppl 4):LBA285.
