FDA Approves Ziihera Regimens for Gastric Cancer

FDA approved two Ziihera-containing regimens on 25 August 2026 for adults with untreated, HER2-positive advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma — moving Jazz Pharmaceuticals' bispecific antibody from a later-line accelerated approval in a different cancer into full, first-line use in one of the more common HER2-positive solid tumors.

From later-line to first-line

Ziihera's first approval, in November 2024, was narrow by design: an accelerated approval for adults who had already been treated for HER2-positive biliary tract cancer, granted on a 52% objective response rate and contingent on a confirmatory trial. The GEA approval is a different kind of submission entirely. It is a full approval, not accelerated; it covers first-line, treatment-naive patients; and it addresses a far larger population — gastric, gastroesophageal junction, and esophageal adenocarcinomas are collectively one of the most common HER2-positive solid tumor settings in oncology. Jazz filed the supplemental BLA covering both regimens, and FDA granted it Priority Review before accepting it for filing in April 2026.

What HERIZON-GEA-01 showed

The trial randomized patients with HER2-positive, unresectable locally advanced or metastatic GEA to one of three arms: trastuzumab plus chemotherapy, the prior standard of care; zanidatamab plus chemotherapy; or zanidatamab plus chemotherapy plus tislelizumab, BeOne Medicines' PD-1 inhibitor. Jazz and its investigators describe HERIZON-GEA-01 as the first Phase 3 study in metastatic GEA to show both a median progression-free survival beyond one year and a median overall survival beyond two — the triplet arm's 26.4-month median OS against the trastuzumab arm's 19.2 months translated to a 28% reduction in the risk of death (HR 0.72; 95% CI, 0.57–0.90; P=.0043). The two-drug zanidatamab-chemotherapy arm also outperformed trastuzumab-chemotherapy on progression-free survival, though the survival benefit was strongest with the triplet. Results were published in the New England Journal of Medicine, alongside the trial's presentation as a late-breaking abstract.

Two regimens, two biomarker cutoffs

• Ziihera + Tevimbra + chemotherapy: approved for HER2+ IHC 3+ or IHC 2+/ISH+ disease — the broader biomarker population, including tumors with lower-intensity HER2 expression confirmed by in situ hybridization.
• Ziihera + chemotherapy alone: approved for HER2+ IHC 3+ disease only — a narrower population, giving prescribers a chemo-immunotherapy-free option where a PD-1 inhibitor may be contraindicated or unwanted.
• Both regimens exclude prior systemic treatment for advanced disease; the approval is specifically for the first-line, treatment-naive setting.

What it means for prescribers

Trastuzumab plus chemotherapy has been the default first-line HER2-positive GEA regimen for more than a decade, since the ToGA trial established it in 2010. A regimen that improves median overall survival by more than seven months against that standard, with a companion option that drops the checkpoint inhibitor entirely, gives oncologists two new first-line paths rather than one. HER2 testing at diagnosis — already standard practice for gastric and gastroesophageal cancers — now has more consequence: the IHC 3+ versus IHC 2+/ISH+ distinction determines which of the two newly approved regimens a patient qualifies for.