Dr Elimova on Key Data for Zanidatamab-Based Combos in HER2+ Gastroesophageal Adenocarcinoma

“These [efficacy data] are not something we have seen in previous gastroesophageal adenocarcinoma studies.”

Elena Elimova, MD, an associate professor in the Department of Medicine at the University of Toronto, as well as a staff medical oncologist at Princess Margaret Hospital, unpacked the most notable findings from the phase 3 HERIZON-GEA-01 trial (NCT05152147), which were presented at the 2026 Gastrointestinal (GI) Cancers Symposium. The trial evaluated zanidatamab-hrii (Ziihera) in combination with chemotherapy with or without tisleizumab (Tevimbra) vs trastuzumab (Herceptin) plus chemotherapy in patients with unresectable, locally advanced, recurrent or metastatic HER2-positive gastroesophageal adenocarcinoma (n = 914).

Elimova began by outlining an overview of the design of the trial, noting that patients in the trial were randomly assigned in a 1:1:1 fashion for each arm. Furthermore, Elimova clarified by noting how patients in either zanidatamab arm received antidiarrheal prophylaxis, based on a data from a phase 2 study (NCT03929666) that also examined zanidatamab plus chemotherapy in HER2-positive gastroesophageal adenocarcinoma. Elimova mentioned that patients were stratified by region, HER2 status, and ECOG performance status, but not by PD-L1 status. The trial had dual primary end points of progression-free survival (PFS) per blinded independent central review and overall survival (OS).

Moving into a discussion on primary end point data, Elimova emphasized that a statisitucally significant improvement in PFS was observed in both zanidatamab arms of the trial. Findings from the trial indicated that patients who received zanidatamab plus tislelizumab and chemotherapy (n = 302) achieved a median PFS of 12.4 months (95% CI, 9.8-18.5) compared with 8.1 months (95% CI, 7.0-8.9) for patients in the trastuzumab plus chemotherapy arm (n = 308; HR, 0.63; 95% CI, 0.51-0.78; P < .0001). Zanidatamab plus tislelizumab and chemotherapy yielded PFS rates of 59.7% (95% CI, 53.6%-65.4%), 43.9% (95% CI, 37.4%-50.1%), and 38.2% (95% CI, 31.4%-45.0%) at 9, 18, and 24 months, respectively, compared with respective rates of 3.7% (95% CI, 37.5%-49.7%), 20.9% (95% CI, 15.3%-27.2%), and 15.6% (95% CI, 10.1%-22.1%) at the same time points in the trastuzumab arm.

Additionally, the median PFS was 12.4 months (95% 9.8-14.5) In the zanidatamab plus chemotherapy arm (n = 304; HR vs trastuzumab arm, 0.65; 95% CI, 0.52-0.81; P < .0001).

Elimova underscored how surpassing 12 months for PFS is a first-time feat in metastatic gastroesophageal adenocarcinoma.

Regarding OS results, zanidatamab-based regimens improved median OS in patients by over 7 months compared with trastuzumab, Elimova noted. The median OS for the zanidatamab plus chemotherapy and tislelizumab arm was 26.4 months (95% CI, 21.5-30.3) vs 19.2 months (95% CI, 16.8-21.8) for the trastuzumab arm (HR, 0.72; 95% CI, 0.57-0.90; P = .0043). Furthermore, the median OS was 24.4 months (95% CI, 20.4-30.0) in the zanidatamab plus chemotherapy arm (HR vs trastuzumab arm, 0.80; 95% CI, 0.64-1.01).

Elimova wrapped up the discussion by mentioning that these findings were generated from the first interim analysis of the study out of three planned, and additional follow-up will provide additional context to these findings.