Phase 3 results — published in NEJM, survival update at ESMO 2026 (LBA79) US FDA approval (2026-08-25) Japan: trial country; this indication not yet under review
Zanidatamab (brand name Ziihera), a new drug for HER2-positive gastric cancer, extended survival compared with the long-standing trastuzumab (Herceptin) regimen in the phase 3 HERIZON-GEA-01 trial of first-line treatment for advanced HER2-positive gastric cancer. Patients who received zanidatamab with the immunotherapy drug tislelizumab and chemotherapy lived a median of 27.0 months, more than 7 months longer than with trastuzumab plus chemotherapy (19.6 months), and their risk of death was 35% lower. The US FDA approved this treatment on August 25, 2026, and nearly three years of follow-up were presented at the European Society for Medical Oncology (ESMO) congress in October 2026.
Zanidatamab is an antibody that grips HER2 at two sites
In some people with gastric cancer, the cancer cells carry large amounts of a protein called HER2. This is HER2-positive gastric cancer, and adenocarcinoma where the stomach meets the esophagus (the gastroesophageal junction) or in the lower esophagus is treated the same way. Since around 2010, the first-line treatment for these patients has been chemotherapy plus trastuzumab, an antibody that targets HER2.
Zanidatamab is a bispecific antibody. Trastuzumab binds one part of HER2, while zanidatamab binds two different parts at the same time. This links HER2 molecules together, blocks growth signals more strongly and appears to help immune cells recognize the cancer. The drug was developed by Zymeworks in Canada and is marketed by Jazz Pharmaceuticals in the US. Tislelizumab (brand name Tevimbra), used alongside it, is an immunotherapy drug that blocks PD-1.
In the US, zanidatamab is already used for HER2-positive biliary tract cancer that has progressed after chemotherapy. For other biliary tract cancer news, see our article on ivonescimab.
Who is it for? Previously untreated advanced HER2-positive gastric cancer
HERIZON-GEA-01 enrolled 914 patients at 225 sites in 33 countries. Japanese hospitals took part (Japan trial registration jRCT2061230026), and the lead investigator is Dr. Kohei Shitara of the Gastrointestinal Oncology department at the National Cancer Center Hospital East in Kashiwa, Japan. About half of the participants were from Asia. Key eligibility criteria were:
- Gastric, gastroesophageal junction or esophageal adenocarcinoma that cannot be removed by surgery or has spread
- HER2 positivity confirmed on a tissue test
- No previous chemotherapy for advanced disease
Patients were split equally into three groups: (1) zanidatamab + tislelizumab + chemotherapy (302 patients), (2) zanidatamab + chemotherapy (304), and (3) trastuzumab + chemotherapy (308). Chemotherapy was capecitabine plus oxaliplatin (CAPOX) or fluorouracil plus cisplatin (FP).
Results: 3-year survival of 39.8%, about 1.7 times the trastuzumab group
The first results were published in the New England Journal of Medicine on May 27, 2026. At ESMO 2026, Dr. Shitara presented updated survival data collected up to July 15, 2026, with a median follow-up of 35.3 months (LBA79).
| Measure | Zanidatamab + tislelizumab + chemo | Zanidatamab + chemo | Trastuzumab + chemo |
|---|---|---|---|
| Median overall survival | 27.0 months | 22.9 months | 19.6 months |
| Hazard ratio for death (vs. trastuzumab) | 0.65 | 0.76 | Reference |
| 3-year survival (estimated) | 39.8% | 31.5% | 22.9% |
| Median progression-free survival | 12.7 months | 12.4 months | 8.3 months |
| Objective response rate (first analysis) | 70.7% | 69.6% | 65.7% |
| Complete response (first analysis) | 19.6% | 17.1% | 11.0% |
| Median duration of response (first analysis) | 20.7 months | 14.3 months | 8.3 months |
Sources: ESMO 2026 LBA79, NEJM 2026 (Shitara et al.). A hazard ratio below 1 favors the treatment. Progression-free survival is the time without cancer growth; a complete response means no visible cancer on scans.
With longer follow-up, the gap for the three-drug combination grew compared with the first analysis (26.4 vs. 19.2 months, hazard ratio 0.72). At the second analysis, the zanidatamab plus chemotherapy group also lived significantly longer than the trastuzumab group (hazard ratio 0.76). The investigators concluded that zanidatamab-based treatment can become a new first-line standard for HER2-positive gastric cancer. The National Cancer Center Japan described the result as showing that strengthening HER2-targeted therapy itself matters.
Side effects: diarrhea prevention starts from the first cycle
The most common side effect is diarrhea. Severe (grade 3 or higher) diarrhea occurred in 24.8%, 20.0% and 12.9% of the three groups. It mostly appeared early, and in the trial patients took an anti-diarrhea medicine (loperamide) preventively during the first cycle. Memorial Sloan Kettering Cancer Center (MSK) notes that it was usually managed with anti-diarrhea medication or chemotherapy dose adjustment, and fewer than 5% of patients stopped the drug because of it.
The US label also advises the following checks:
- Heart function: left ventricular function is checked (for example with an echocardiogram) before and during treatment. A decline was reported in 9% (with tislelizumab) and 5% (with chemotherapy).
- Infusion reactions: fever or chills can occur during the infusion, so preventive medicines are given before each dose. These were reported in 22–24%.
- Pregnancy: the drug can harm a fetus, so contraception is needed during treatment and for 4 months after the last dose.
When tislelizumab is added, immune-related side effects (such as thyroid, skin or lung inflammation) can occur, so regular blood tests are used to monitor them. For other treatments in the gastroesophageal area, see our article on proton therapy for esophageal cancer.
Where is it available? Approved in the US; Japan took part in the trial
- United States: On August 25, 2026, the FDA approved it as first-line treatment for advanced HER2-positive gastroesophageal adenocarcinoma. The tislelizumab combination can be used for HER2 IHC 3+ or IHC 2+ with a positive gene test (ISH), regardless of PD-L1 results. The chemotherapy-only combination is for IHC 3+ patients.
- Japan: Japanese hospitals took part in this phase 3 trial, and a Japanese investigator led the results. No Japanese application for this gastric cancer indication has been announced yet. In Japan, trastuzumab plus chemotherapy plus pembrolizumab is approved and in use for PD-L1-positive HER2-positive gastric cancer.
- Europe and elsewhere: Zanidatamab is approved for another indication in the European Union and other countries, and the company is pursuing further approvals for gastric cancer.
For other HER2-targeted drug news, see our article on tucatinib maintenance for HER2-positive breast cancer.
What to check and questions for your doctor
- Is my HER2 result IHC 3+ or 2+? If 2+, was an ISH test done?
- What was my PD-L1 result, and which first-line treatments are available to me now?
- Can I receive a zanidatamab combination in my country or in Japan? Is there a clinical trial I could join?
- Which medicine should I take for diarrhea, and when should I call the hospital?
- How often will my heart be checked during treatment?
Frequently asked questions
What is zanidatamab, the new drug for HER2-positive gastric cancer?
It is a bispecific antibody given by infusion that binds two different parts of the HER2 protein at once. Sold as Ziihera, it is designed to block HER2 signaling more strongly than trastuzumab in HER2-positive gastric cancer.
What did the HERIZON-GEA-01 trial show?
In this phase 3 trial of 914 patients, median survival with zanidatamab, tislelizumab and chemotherapy was 27.0 months versus 19.6 months with trastuzumab and chemotherapy, a 35% lower risk of death. Three-year survival was 39.8% versus 22.9%.
How are zanidatamab side effects managed?
Diarrhea, the most common side effect, usually appears early. It is managed by taking an anti-diarrhea medicine from the first cycle and adjusting doses when needed. Heart function tests and pre-infusion medicines are also part of treatment.
Can I receive zanidatamab in Japan?
Japanese hospitals took part in the phase 3 trial, and the lead investigator is a doctor at the National Cancer Center Japan. There is no Japanese approval for the gastric cancer indication yet; trastuzumab-based treatment is currently covered by insurance.
Related: Tarlatamab phase 3 in small cell lung cancer · Photodynamic therapy for esophageal cancer · All cancer-type articles
Sources
- NEJM — Shitara K, et al. Zanidatamab with or without tislelizumab plus chemotherapy in HER2-positive gastroesophageal adenocarcinoma (HERIZON-GEA-01, 2026)
nejm.org
Checked: 2026-11-03 - OncoDaily — HERIZON-GEA-01 at ESMO 2026: Updated Overall Survival (LBA79)
oncodaily.com
Checked: 2026-11-03 - Jazz Pharmaceuticals — U.S. FDA Approves Ziihera (zanidatamab-hrii) with and without Tislelizumab plus Chemotherapy in First-Line HER2+ Advanced GEA (2026-08-25)
investor.jazzpharma.com
Checked: 2026-11-03 - National Cancer Center Japan — Zanidatamab combinations prolong survival in first-line HER2-positive gastric cancer (2026-05-28, Japanese)
ncc.go.jp
Checked: 2026-11-03 - Memorial Sloan Kettering — FDA Approves Zanidatamab for HER2-Positive Cancers of the Stomach and Esophagus (2026-09-04)
mskcc.org
Checked: 2026-11-03 - OncLive — Zanidatamab Plus Chemo ± Tislelizumab Improves Survival in HER2+ Gastroesophageal Adenocarcinoma
onclive.com
Checked: 2026-11-03 - Targeted Oncology — Zanidatamab plus chemotherapy shows OS benefit at second interim analysis (2026-09-01)
targetedonc.com
Checked: 2026-11-03 - ClinicalTrials.gov — NCT05152147: HERIZON-GEA-01
clinicaltrials.gov/study/NCT05152147
Checked: 2026-11-03 - jRCT — jRCT2061230026: HERIZON-GEA-01 (Japan)
jrct.mhlw.go.jp
Checked: 2026-11-03
Written by the FTH editorial team. Sources checked 2026-11-03 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
