In a global phase 3 study of patients with HER2-positive advanced or metastatic gastroesophageal junction adenocarcinoma, combination therapy with zanidatamab (sold as Ziihera in the U.S.) significantly improved progression-free survival (PFS) and overall survival (OS) compared with the standard of care, trastuzumab-based chemotherapy.
The combination of zanidatamab, Tevimbra (tislelizumab), and chemotherapy showed consistent survival benefits across PD-L1 expression levels, suggesting potential as a first-line standard therapy
BeOne Medicines announced the topline results of the zanidatamab-based phase 3 HERIZON-GEA-01 study on Monday, local time.
The study compared Ziihera plus chemotherapy, Ziihera plus Tevimbra plus chemotherapy, and trastuzumab plus chemotherapy in 914 patients with HER2-positive gastric cancer, gastroesophageal junction cancer, or esophageal adenocarcinoma. PFS and OS were the primary endpoints.
According to the company, patients lived longer without disease progression in both the Ziihera + Tevimbra + chemotherapy arm and the Ziihera + chemotherapy arm compared with the control group. Overall survival improved significantly in the triple-therapy arm, while the Ziihera + chemotherapy arm showed a trend toward clinically meaningful improvement. Response rates and response duration were also higher in both Ziihera arms than in the control arm.
“Advanced gastroesophageal junction cancer remains an area with poor treatment outcomes, and no new HER2-targeted options have emerged in the past 15 years,” said Professor Rha Sun-young of Yonsei Cancer Hospital, a study investigator.
These results represent a major step forward, with the potential to shift the first-line treatment paradigm, Professor Rha said. Consistent survival benefits in both PD-L1-positive and PD-L1-negative patients further strengthen its real-world applicability, she added.
BeOne Medicines said, “These findings mark meaningful progress in a field with substantial unmet needs. We will engage with regulators as quickly as possible in regions where we hold Ziihera rights and seek expanded indications for the Ziihera-Tevimbra combination.”
Safety results were consistent with Ziihera’s known safety profile, and no new safety concerns emerged in either Ziihera regimen. An additional interim OS analysis for the Ziihera + chemotherapy arm is planned for mid-2024.
HERIZON-GEA-01 is a global, randomized phase 3 trial conducted at more than 300 sites in over 30 countries. Detailed results are expected to be presented at major international oncology conferences early next year.