HER2-Positive Gastric Cancer Clinical Trials (May 2026)

Last updated: May 7, 2026

Why HER2 Status Defines a Different Trial Pathway

Roughly 15–22% of gastric and GEJ adenocarcinomas overexpress HER2 (ERBB2), and that one biomarker opens an entirely separate treatment pathway with its own approved drugs and its own clinical trial pipeline. If you're HER2-positive, the trials worth looking at are different from the ones for HER2-negative or CLDN18.2-positive disease.

HER2 testing required: IHC 3+, or IHC 2+ with positive ISH/FISH for gene amplification. Almost all HER2-targeted trials require this confirmation. If your tumor is IHC 1+ or IHC 0, you're "HER2-low" or "HER2-zero" and a separate set of trials applies (especially for trastuzumab deruxtecan in HER2-low expansion cohorts).

Current Trial Landscape (May 2026)

Active research areas:

T-DXd (trastuzumab deruxtecan) moving into first-line combinations — not just second-line monotherapy anymore
Next-generation HER2 ADCs (disitamab vedotin, BL-M07D1, SHR-A1811, IAH0968) testing whether different payloads or linkers improve on T-DXd
Anti-HER2 monoclonal antibody combinations (HLX22 + trastuzumab, others) layering biparatopic or different-epitope HER2 antibodies on top of trastuzumab
Adding immunotherapy (nivolumab, tislelizumab, pembrolizumab) to HER2-targeted backbones at every line of therapy
Earlier perioperative use of HER2 ADCs (locally advanced, before surgery) instead of waiting for metastatic disease

Standard of care (2026): First-line metastatic HER2+ — trastuzumab + fluoropyrimidine/platinum chemo + pembrolizumab (the KEYNOTE-811 regimen, median OS ~20 months). Second-line and beyond — trastuzumab deruxtecan (T-DXd, DESTINY-Gastric series). HER2-low: T-DXd has activity in expansion cohorts. Locally advanced/perioperative: adding HER2-targeted therapy to FLOT or SOX is being tested in multiple Phase 3 trials.

Recruiting Trials by Treatment Setting

First-Line Metastatic HER2+

Building on the KEYNOTE-811 standard — testing whether HER2 ADCs or new HER2 antibodies improve on trastuzumab + chemo + pembrolizumab:

HER2 ADCs in first line:
- NCT06731478 — Trastuzumab deruxtecan + chemo + pembrolizumab + trastuzumab in 1L HER2+ metastatic (Phase 3)
- NCT06764875 — Rilvegostomig + fluoropyrimidine + trastuzumab deruxtecan (Phase 3)
- NCT07118527 — SHR-A1811 (HER2 ADC) + chemo + adebrelimab vs trastuzumab + chemo + pembrolizumab in untreated HER2+ gastric/GEJ (Phase 3, head-to-head against KEYNOTE-811 regimen)
New HER2 antibodies + trastuzumab:
- NCT06532006 — HLX22 + trastuzumab + chemo in HER2+ gastric (Phase 3)
- NCT07315750 — Disitamab vedotin + trastuzumab + tislelizumab vs chemo + trastuzumab ± pembrolizumab in 1L HER2-high (typically IHC 3+) advanced gastric/GEJ (Phase 3)
- NCT06504732 — IAH0968 + CAPEOX in HER2-positive gastric cancer (Phase 3)

Second-Line and Beyond — HER2 ADCs

After progression on first-line trastuzumab-based therapy — next-gen ADCs are the most active area:

NCT07152405 — BL-M07D1 (HER2 ADC) vs investigator's choice of chemo in HER2-positive gastric/GEJ after failure of first-line anti-HER2 therapy + chemo (Phase 3)

Locally Advanced / Perioperative (HER2+)

Most perioperative gastric trials don't pre-select for HER2 status, but several now stratify by HER2 or have HER2-specific arms. For broader gastric perioperative trials with HER2-stratified arms, see the gastric cancer trials page — look for "HER2-positive cohort" language in eligibility.

Showing selected notable HER2-specific trials. View all recruiting HER2+ gastric cancer trials on ClinicalTrials.gov (~150 total).

Frequently Asked Questions

What does HER2-positive mean in gastric cancer?

HER2-positive gastric cancer means the tumor overexpresses HER2 (ERBB2) protein, defined as IHC 3+ or IHC 2+ with a positive ISH/FISH test confirming gene amplification. Roughly 15–22% of gastric cancers are HER2-positive, and HER2 status is required for trastuzumab-based and HER2 ADC trials.

What is the standard first-line treatment for HER2+ metastatic gastric cancer in 2026?

Trastuzumab + fluoropyrimidine/platinum chemotherapy + pembrolizumab (the KEYNOTE-811 regimen). This combination has shifted median overall survival from ~13 months on chemo + trastuzumab alone to roughly 20 months.

What clinical trials are available for HER2+ gastric cancer?

Approximately 150 recruiting interventional trials for HER2-positive gastric cancer are available in 2026, including trastuzumab deruxtecan (T-DXd) earlier-line combinations, disitamab vedotin, next-generation HER2 ADCs (BL-M07D1, SHR-A1811, IAH0968, HLX22), and HER2 + immunotherapy combinations.

Can my tumor be tested again if HER2 was negative the first time?

Yes, and it's worth doing. HER2 status can be heterogeneous (different parts of the tumor can score differently), and re-testing on a new biopsy — especially after progression on first-line therapy — sometimes reveals HER2 positivity that was missed initially. Some trials specifically allow repeat testing for eligibility.

What about HER2-low gastric cancer?

HER2-low (IHC 1+ or IHC 2+/ISH-) is increasingly being studied as a separate group, especially for trastuzumab deruxtecan. Several trials have HER2-low expansion cohorts. If your IHC is 1+ or 2+/ISH-negative, ask your oncologist specifically about HER2-low trials — eligibility differs from HER2-positive.

Find HER2+ Gastric Cancer Trials Matched to Your Situation

Use ClinTrialFinder's AI-powered matching to find trials based on your HER2 status, prior treatments, and other biomarkers.

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