Core Insights - Zymeworks Inc. announced positive efficacy and safety results from the Phase 3 HERIZON-GEA-01 trial for Ziihera® (zanidatamab-hrii) in combination with chemotherapy for HER2-positive gastroesophageal adenocarcinoma [1][3] Efficacy Summary - Ziihera plus chemotherapy, with or without the PD-1 inhibitor tislelizumab, showed a statistically significant and clinically meaningful prolongation of progression-free survival (PFS) with a 35% reduction in the risk of disease progression or death compared to trastuzumab plus chemotherapy, resulting in a median PFS of over one year, which is more than a four-month improvement [5][6] - The overall survival (OS) benefit for Ziihera plus tislelizumab and chemotherapy was significant, with a median OS of 26.4 months, representing a greater than seven-month improvement compared to trastuzumab plus chemotherapy [5][6] - The study demonstrated consistent PFS and OS benefits across major prespecified subgroups, including geographic region and PD-L1 status [5][6] Safety Profile - The safety profile of Ziihera in combination with chemotherapy was consistent with known effects of HER2-directed therapy, with no new safety signals identified [7] - Grade ≥3 treatment-related adverse events (TRAEs) were reported at 71.8% for Ziihera plus tislelizumab and chemotherapy, 59.0% for Ziihera plus chemotherapy, and 59.6% for trastuzumab plus chemotherapy [7] - The most common Grade ≥3 TRAE was diarrhea, with rates of 24.5% for Ziihera plus tislelizumab and chemotherapy [7] Financial Implications - Zymeworks is eligible to receive up to $440 million in milestone payments related to regulatory approvals of Ziihera in gastroesophageal adenocarcinoma across various regions, including $250 million from the United States [4][8] - The company anticipates increased royalty revenue from Ziihera sales as regulatory approvals are obtained in global markets [8] Trial Overview - The HERIZON-GEA-01 trial is a global, randomized, open-label Phase 3 study evaluating Ziihera plus chemotherapy, with or without tislelizumab, against trastuzumab plus chemotherapy for adult patients with advanced HER2-positive gastroesophageal adenocarcinoma [9] - The trial involved 914 patients from approximately 300 sites in over 30 countries [9] Industry Context - Gastroesophageal adenocarcinoma (GEA) is the fifth most common cancer globally, with a poor prognosis and a five-year survival rate of less than 30% for gastric cancer [10]