FDA approves zanidatamab-hrii and tislelizumab-jsgr for HER2-positive gastric, gastroesophageal junction, or esophageal adenocarcinoma

Regulatory approval: On Aug 25, 2026, the FDA approved zanidatamab-hrii (Ziihera) with fluoropyrimidine/platinum chemotherapy and tislelizumab-jsgr (Tevimbra) as first-line treatment for adults with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (FDA-approved test required). Zanidatamab-hrii with chemotherapy was also approved for HER2-positive IHC 3+ disease. Approvals were supported by HERIZON-GEA-01 efficacy and safety results.

FDA approval (Aug 25, 2026)

The FDA approved zanidatamab-hrii (Ziihera) in:

  • Combination with fluoropyrimidine- and platinum-containing chemotherapy and tislelizumab-jsgr (Tevimbra) for first-line treatment of adults with HER2-positive (IHC 3+ or IHC 2+/ISH+) unresectable locally advanced or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma, as detected by an FDA-approved test.
  • Combination with fluoropyrimidine- and platinum-containing chemotherapy for first-line treatment of adults with HER2-positive (IHC 3+) unresectable locally advanced or metastatic gastric/GEJ/esophageal adenocarcinoma, as detected by an FDA-approved test.

The FDA also approved companion diagnostics: PATHWAY anti-HER-2/neu (4B5) and VENTANA HER2 Dual ISH DNA Probe Cocktail to identify HER2-positive (IHC3+ or IHC2+/ISH+) gastric/GEJ/esophageal adenocarcinoma for Ziihera, consistent with labeling.

Key evidence: HERIZON-GEA-01 (NCT05152147)

Randomized (1:1:1), open-label trial comparing:

  • Arm A: trastuzumab + CAPOX or FP
  • Arm B: zanidatamab-hrii + CAPOX or FP
  • Arm C: zanidatamab-hrii + tislelizumab-jsgr + CAPOX or FP

Dual major endpoints were PFS (BICR, RECIST v1.1) and OS. Arm C vs Arm A showed significant benefit in HER2 IHC3+ or IHC2+/ISH+ tumors: median OS 26.4 vs 19.2 months (HR 0.72; p=0.0043) and median PFS 12.4 vs 8.1 months (HR 0.63; p<0.0001). Arm B improved PFS vs Arm A; OS interim results were not statistically significant at the time of PFS analysis.

Safety highlights (labeling)

Zanidatamab-hrii includes a boxed warning for diarrhea and embryo-fetal toxicity; warnings include left ventricular dysfunction and infusion-related reactions. Tislelizumab-jsgr warnings include immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic HSCT, and embryo-fetal toxicity.

Review used Project Orbis and RTOR; reviews remain ongoing at partner agencies.

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