HER2-positive gastric cancer is entering a new phase of competition. In the United States, the FDA’s August 2026 approval of two zanidatamab-based first-line regimens changed the treatment landscape. In Japan, trastuzumab deruxtecan (Enhertu) is now available in the second-line setting, following a label expansion earlier this year. These developments are shifting the strategic question for drug developers: how can a new therapy improve on, complement, or outlast an increasingly crowded set of HER2-directed options?
The answer will depend on more than the drug target. Trial results, treatment line, HER2 testing criteria, combination partners, and local regulatory status will all shape a therapy’s prospects. For companies developing antibody-drug conjugates (ADCs), bispecific antibodies or immune-based combinations, the competitive benchmark has moved.
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What is changing in HER2-positive gastric cancer?
HER2, also called ERBB2, is a protein that can drive tumor growth when it is overexpressed or amplified. In advanced gastric and gastroesophageal junction (GEJ) adenocarcinoma, HER2 status helps guide treatment selection. The FDA approval covers tumors classified as IHC 3+ or IHC 2+/ISH-positive for the zanidatamab, tislelizumab and chemotherapy combination. The zanidatamab and chemotherapy regimen without tislelizumab is approved for IHC 3+ disease.
That distinction matters commercially. A therapy’s eligible population depends on how its label defines HER2 positivity, how reliably patients are tested, and whether results are available in time to guide first-line treatment. In September 2026, the FDA also approved two Roche companion diagnostic tests to help identify patients for the new zanidatamab-based indication. Testing is therefore part of the treatment’s launch story, not a background laboratory detail.
The competitive field also extends beyond first-line treatment. Enhertu has established a role after prior trastuzumab-based therapy, while clinical trials are testing whether it and other HER2-directed medicines can be used earlier or combined with chemotherapy and immunotherapy. Each new regimen will need to show where it fits: before progression, after progression, or for patients whose tumors meet a more specific biomarker definition.
The U.S. and Japan: two different strategic settings
The U.S. has a newly approved first-line zanidatamab option, creating a fresh commercial and clinical benchmark for advanced HER2-positive disease. The FDA evaluated the regimens in HERIZON-GEA-01, a global Phase 3 study. In the trial, the zanidatamab, tislelizumab, and chemotherapy arm had median overall survival of 26.4 months, compared with 19.2 months in the trastuzumab and chemotherapy control arm. Median progression-free survival was 12.4 months versus 8.1 months. These are trial results in the studied population, not a guarantee of the same outcome for every patient.
Japan has a substantial gastric cancer burden, but the country’s total stomach cancer statistics should not be confused with HER2-positive case numbers. Japan’s National Cancer Center reports 104,864 new stomach cancer diagnoses in 2023 and 37,867 stomach cancer deaths in 2024. Those figures cover stomach cancer overall, not the HER2-positive subgroup.
Japan’s treatment sequence has also recently changed. In March 2026, Daiichi Sankyo announced that Enhertu became available in Japan for second-line treatment of eligible HER2-positive advanced or recurrent gastric cancer after review of DESTINY-Gastric04 data. That makes the Japanese second-line environment different from a simple copy of the U.S. pathway. Any company assessing the two markets should evaluate Japanese regulatory status, local treatment practice and trial availability separately. An FDA approval does not establish Japanese approval or availability.
Recent developments to watch
August 25, 2026 - FDA approves two first-line zanidatamab regimens.
The U.S. approval allows zanidatamab with chemotherapy and tislelizumab for eligible HER2-positive gastric, GEJ or esophageal adenocarcinoma. It also allows zanidatamab with chemotherapy for the IHC 3+ group. The different testing criteria make companion diagnostics and patient identification important parts of the commercial opportunity.
August 31, 2026 - BeOne reports a positive second interim analysis.
BeOne Medicines announced positive topline results from the second interim analysis of HERIZON-GEA-01, evaluating zanidatamab with chemotherapy, with or without tislelizumab, as first-line treatment. The update reinforces the importance of survival evidence in the competition around this regimen.
September 23, 2026 - Roche companion diagnostics receive FDA approval.
The PATHWAY HER2 (4B5) test and VENTANA HER2 Dual ISH test were approved to help identify eligible patients. This development highlights a practical issue for commercial adoption: treatment access depends on appropriate testing as well as the drug label.
September 28, 2026 - ALX Oncology publishes ASPEN-06 Phase 2 data.
The company reported an objective response rate of 40.3% with evorpacept added to trastuzumab, ramucirumab and paclitaxel, compared with 26.6% for the control regimen. In a subgroup with retained HER2-positive disease and high CD47 expression, the reported response rates were 63.6% and 23.1%. This is an investigational Phase 2 signal. Further development and confirmation would be needed before it could change treatment practice.
July 27, 2026 - AstraZeneca reports adjacent gastric cancer competition.
AstraZeneca announced a Phase 3 survival result for sonesitatug vedotin in CLDN18.2-positive advanced gastric/GEJ cancer. This is not a HER2-positive program, but it is relevant context: other biomarker-defined therapies are also competing for treatment decisions and investment in gastric cancer.
Top 10 companies shaping the competitive landscape
The following watchlist reflects strategic relevance across approved treatment, active trials, diagnostics and emerging programs. It is not a ranking by market share.
| Company | Program or role | Why it matters |
Jazz Pharmaceuticals and Zymeworks | Zanidatamab (Ziihera) | Zanidatamab’s first-line U.S. approval gives the companies a new position in advanced HER2-positive disease. |
| BeOne Medicines | Tislelizumab (Tevimbra) | Its immunotherapy is part of the FDA-approved zanidatamab combination; BeOne also reported the HERIZON-GEA-01 interim update. |
Daiichi Sankyo and AstraZeneca | Trastuzumab deruxtecan (Enhertu) | The ADC has a second-line role and is being evaluated in first-line combinations, including the Phase 3 DESTINY-Gastric05 study. |
| Merck & Co. | Pembrolizumab | It is relevant to first-line combination strategies and the KEYNOTE-811 treatment framework. |
| Roche | HER2 diagnostics | Its FDA-approved companion diagnostic tests connect biomarker testing to the new U.S. treatment indication. |
| Henlius | HLX22 | The anti-HER2 antibody is in a Phase 3 first-line study with trastuzumab and chemotherapy. |
RemeGen and Pfizer | Disitamab vedotin (RC48) | This ADC has gastric cancer development in China and an international licensing arrangement with Pfizer. |
| ALX Oncology | Evorpacept | ASPEN-06 offers a Phase 2 combination signal and a potential biomarker angle around CD47 expression. |
| Jiangsu Hengrui | SHR-A1811 | This HER2-directed ADC is an earlier-stage gastric/GEJ program to monitor as clinical evidence develops. |
| Bio-Thera Solutions | BL-M07D1 | A Phase 3 trial is evaluating the ADC after failure of first-line anti-HER2 therapy. |
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Pipeline analysis: where the next decisions will be made
1. First-line treatment is now the key battleground
Zanidatamab-based regimens have established a new U.S. first-line option. That raises the evidence bar for future entrants. A new regimen will need to demonstrate a meaningful advantage, identify a patient group with a distinct need, or offer a practical difference in safety, administration or treatment sequencing.
2. ADC developers are testing earlier use
T-DXd is moving beyond its established post-trastuzumab setting through first-line clinical development. The central question is whether an ADC-based combination can improve outcomes enough to justify its place earlier in treatment. The answer will depend on Phase 3 results, tolerability, and how the regimen compares with current first-line combinations.
3. Next-generation antibodies and ADCs bring different evidence needs
HLX22 adds a different anti-HER2 antibody to trastuzumab and chemotherapy, while BL-M07D1 is being evaluated after first-line treatment failure. Disitamab vedotin and SHR-A1811 represent ADC approaches, but their current trial stages, geographies, and development plans differ. For decision-makers, the useful comparison is not simply “which asset targets HER2?” It is what evidence each program is generating, for which patients, and in which treatment line.
4. Biomarker strategy could influence the next wave
ASPEN-06 puts a spotlight on the possibility that CD47 expression may help identify patients more likely to benefit from an evorpacept combination. That finding is still investigational, but it points to a broader development challenge: HER2 status alone may not be enough to define the best treatment for every patient. Further studies will need to test whether additional biomarkers can reliably guide treatment choices.
5. Japan requires a country-specific development and access view
Japan’s recent Enhertu label expansion shows why companies should map local treatment sequence and approval status rather than assume the U.S. pathway applies. Japan also has a high total burden of stomach cancer, making the local clinical setting important, while HER2-positive subgroup estimates and eligible patient numbers should be sourced separately.
What executives should monitor next?
The next meaningful signals will include Phase 3 readouts for first-line ADC combinations, progress in late-stage programs such as HLX22 and BL-M07D1, and whether evorpacept advances into a gastric cancer registration study. In parallel, companies should track diagnostic requirements and country-specific regulatory developments.
The strategic shift is clear: HER2-positive gastric cancer is becoming a contest over treatment sequence, combination design and patient selection. For companies active in the U.S. and Japan, the most useful question is not just which drug has the strongest early signal. It is which program can produce the right evidence, for the right patients, in the right market.
Frequently Asked Questions
What is HER2-positive gastric cancer?
It is gastric or GEJ adenocarcinoma in which testing shows HER2 overexpression or amplification. For the U.S. zanidatamab-based first-line regimens, the FDA label specifies IHC 3+ or IHC 2+/ISH-positive disease for the regimen that includes tislelizumab, and IHC 3+ for zanidatamab with chemotherapy.
Which companies are developing or commercializing HER2-positive gastric cancer treatments?
Companies to watch include Jazz Pharmaceuticals, Zymeworks, BeOne Medicines, Daiichi Sankyo, AstraZeneca, Henlius, RemeGen, Pfizer, ALX Oncology, Jiangsu Hengrui and Bio-Thera. Roche is also relevant through companion diagnostics.
What are the leading HER2-positive gastric cancer pipeline approaches?
The landscape includes bispecific antibodies, HER2-directed ADCs, additional anti-HER2 antibodies and combinations involving immunotherapy or other targeted mechanisms. Their trial phases and treatment settings vary, so pipeline comparisons should specify the patient group and line of therapy.
What is the main difference between the U.S. and Japan landscapes?
The U.S. has an FDA-approved first-line zanidatamab option as of August 2026. Japan’s treatment pathway should be assessed separately; Enhertu became available for second-line treatment there in March 2026. Local approval, testing and treatment practices should be verified independently.