Zymeworks’ Ziihera shows efficacy in Phase 3 adenocarcinoma trial

Zymeworks (ZYME) announced positive topline results from the Phase 3 HERIZON-GEA-01 trial evaluating Ziihera – zanidatamab-hrii – in combination with chemotherapy, with or without the PD-1 inhibitor Tevimbra – tislelizumab -, as a first-line treatment for HER2-positive locally advanced or metastatic gastroesophageal adenocarcinoma, including cancers of the stomach, gastroesophageal junction, and esophagus. Results were announced by Zymeworks’ development and commercialization partners, Jazz Pharmaceuticals (JAZZ) and BeOne Medicines (ONC). Both Ziihera plus chemotherapy and Ziihera plus Tevimbra and chemotherapy demonstrated highly statistically significant and clinically meaningful improvements in progression-free survival vs. the control arm, trastuzumab plus chemotherapy. Ziihera plus Tevimbra and chemotherapy also demonstrated clinically meaningful and statistically significant improvements in overall survival, and Ziihera plus chemotherapy demonstrated a clinically meaningful effect with a strong trend toward statistical significance for OS compared to the control arm at the time of this first analysis. The trial is ongoing with an additional planned OS interim analysis for Ziihera plus chemotherapy currently expected in mid-2026. A PFS and OS benefit was observed in the Ziihera plus Tevimbra and chemotherapy arm versus the control arm in both PD-L1 positive and PD-L1 negative subgroups. Both Ziihera plus Tevimbra and chemotherapy, and Ziihera plus chemotherapy demonstrated improvements in the key secondary endpoints of objective response rate and duration of response vs. the control arm and these endpoints were supportive of the primary efficacy endpoints. The safety profile of Ziihera was generally consistent with the known safety profile of each agent with no new safety signals observed. Jazz plans to submit these data for presentation at a major medical meeting in Q1 2026 and for publication in a peer-reviewed journal, and will rapidly submit for adoption in the National Comprehensive Cancer Network Guidelines. Jazz expects to submit a supplemental Biologics License Application in the first half of 2026 to support Ziihera as a first-line treatment for patients with HER2+ locally advanced or metastatic GEA for use as part of a standard chemotherapy regimen with or without Tevimbra. Zanidatamab is currently approved in the U.S., Europe and China for use in second-line biliary tract cancer and is marketed under the trade name, Ziihera, by Jazz and BeOne. Zymeworks is eligible for additional regulatory and commercial milestones, as well as tiered royalties on net sales of Ziihera from Jazz and BeOne.