FDA Approves Zanidatamab and Tislelizumab for HER2-Positive GI Cancers

A simultaneous dual-drug, dual-diagnostic approval from FDA on August 25, 2026, lands squarely on the desks of QA directors and labeling teams: zanidatamab-hrii (Ziihera, Jazz Pharmaceuticals) and tislelizumab-jsgr (Tevimbra, BeOne Medicines USA) are now approved in combination with fluoropyrimidine- and platinum-containing chemotherapy as first-line treatment for adults with HER2-positive unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma. The approval introduces layered complexity that extends well beyond the clinical indication.

For manufacturing and regulatory operations teams, the biosimilar-style four-letter suffixes, hrii and jsgr, carry immediate labeling and pharmacovigilance implications. Both suffixes must appear consistently across batch records, labeling artwork, and adverse event reporting systems. Contract manufacturers and brand sites alike will need to audit SOPs that govern INN suffix handling to ensure alignment with 21 CFR Part 211 labeling requirements before product reaches distribution.

The companion diagnostic dimension adds a second compliance layer. FDA simultaneously approved two Ventana Medical Systems/Roche Diagnostics devices, the PATHWAY anti-HER-2/neu (4B5) Rabbit Monoclonal Primary Antibody and the VENTANA HER2 Dual ISH DNA Probe Cocktail, for identifying HER2-positive patients eligible for Ziihera. Zanidatamab-hrii's label covers IHC 3+ or IHC 2+/ISH+ patients; tislelizumab-jsgr's label is restricted to IHC 3+ only. QA teams coordinating with clinical sites must ensure diagnostic device references in prescribing information and promotional labeling reflect these distinct thresholds precisely, as conflation of the two scoring criteria would constitute a labeling deviation.

Efficacy data from the HERIZON-GEA-01 trial (NCT05152147) underpins both approvals. In the three-arm, randomized, open-label global study, the zanidatamab-hrii plus tislelizumab-jsgr arm (Arm C) demonstrated median OS of 26.4 months versus 19.2 months for the trastuzumab comparator arm (HR 0.72; p=0.0043), with median PFS of 12.4 versus 8.1 months (HR 0.63; p<0.0001). Zanidatamab-hrii monotherapy (Arm B) achieved a statistically significant PFS benefit in IHC 3+ patients, with median PFS of 14.2 versus 7.6 months (HR 0.55), though OS interim results were not statistically significant at the time of PFS analysis.

Dosing for zanidatamab-hrii is weight-based: patients under 70 kg receive 1,800 mg every three weeks or 1,200 mg every two weeks; patients at or above 70 kg receive 2,400 mg every three weeks or 1,600 mg every two weeks. Prescribing information for zanidatamab-hrii carries a boxed warning for diarrhea and embryo-fetal toxicity; tislelizumab-jsgr's label includes warnings for immune-mediated adverse reactions and infusion-related reactions, both of which have direct implications for pharmacovigilance reporting workflows.

Full prescribing information for both products will be posted to Drugs@FDA, and QA and regulatory affairs teams should treat that posting as the trigger for label reconciliation across all affected systems.

Source: FDA Drugs@FDA / What's New: Drugs RSS Feed, August 25, 2026.