Dr Wainberg on the FDA Approval of Zanidatamab for HER2+ Gastric Cancer

“This [approval] presents some options, and options are good; [they] will probably need to be tailored according to individual patients.”

Zev A. Wainberg, MD, a professor of medicine at UCLA and co-director of the UCLA GI Oncology Program, discussed the mechanism of the HER2-directed bispecific antibody zanidatamab-hrii (Ziihera) and what its recent FDA approval means for patients with newly diagnosed metastatic HER2-positive gastric cancer.

Zanidatamab is a bispecific antibody, a term that means different things across different drugs, Wainberg noted. In this case, the antibody binds 2 separate epitopes of the HER2 domain: the site typically bound by trastuzumab (Herceptin) and a second extracellular domain typically bound by pertuzumab (Perjeta), he explained. By engaging both with a single molecule, zanidatamab is designed to more effectively inhibit HER2 signaling and shut down that signal transduction pathway, according to Wainberg.

On August 25, 2026, the FDA approved zanidatamab plus fluoropyrimidine- and platinum-containing chemotherapy, with or without tislelizumab-jsgr (Tevimbra), for patients with frontline HER2-positive unresectable locally advanced or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma, based on findings from the phase 3 HERIZON-GEA-01 trial (NCT05152147). In the trial, the zanidatamab/tislelizumab/chemotherapy triplet (n = 302) improved median progression-free survival to 12.4 months (95% CI, 9.8-18.5) vs 8.1 months (95% CI, 7.0-8.9) with trastuzumab plus chemotherapy (n = 308; HR, 0.63; 95% CI, 0.51-0.78; P < .0001) and improved the median overall survival to 26.4 months (95% CI, 21.5-30.3) vs 19.2 months (95% CI, 16.8-21.8), respectively (HR, 0.72; 95% CI, 0.57-0.90; P = .0043).

For Wainberg, the approval presents the field with additional treatment options, which he said is generally a positive development. Those options will likely need to be tailored to individual patients, he stated.Wainberg also pointed to ongoing phase 3 trials in this space that could further change the landscape over the next few years. Efforts to develop and properly study drugs that meet the end points of these trials deserve consideration, he concluded.