A phase 2 trial reports high response rates and durable outcomes in treatment-naive patients, presented at the American Society of Clinical Oncology [ASCO] 2025 annual meeting.
A multinational phase 2 trial has demonstrated promising efficacy and manageable safety of the bispecific HER2-targeted antibody zanidatamab in combination with standard chemotherapy for the first-line treatment of HER2-positive advanced gastro-oesophageal adenocarcinoma.
The study, published following completion of enrolment (ClinicalTrials.gov: NCT03929666), enrolled 46 treatment-naive patients across Canada, South Korea, and the USA with HER2-positive (IHC 3+ or 2+ with FISH+) metastatic or advanced gastro-oesophageal adenocarcinoma. Patients received zanidatamab intravenously alongside standard regimens including CAPOX, FP, or mFOLFOX6.
IS TISSUE THE ISSUE?
At a median follow-up of nearly four years (47.9 months), the confirmed objective response rate (ORR) was 76.2% (95% CI 60.5–87.9), with a median duration of response of 18.7 months. The median progression-free survival (PFS) reached 12.5 months (95% CI 8.2–21.8), while median overall survival (OS) extended to 36.5 months (95% CI 23.6–not estimable). Disease control rate stood at 88.1%, and clinical benefit rate was 78.6%.
Importantly, no dose-limiting toxicities (DLTs) were observed in patients treated with zanidatamab plus CAPOX, establishing the regimen’s tolerability. However, DLTs were reported in the FP and mFOLFOX6–1 arms, with grade 3 diarrhoea and acute kidney injury among the notable events.
Overall, 65% of patients experienced grade 3 or 4 treatment-related adverse events, with diarrhoea (39%) and hypokalaemia (22%) being the most common. Introduction of mandatory antidiarrhoeal prophylaxis reduced the incidence of severe diarrhoea from 39% to 24%. No treatment-related deaths were reported.
“If these results are confirmed in a large-scale, randomised, phase 3 trial, zanidatamab could represent a substantial advancement in the treatment of HER2-positive advanced gastro-oesophageal adenocarcinoma,” the authors concluded. “
Zanidatamab, a novel bispecific antibody targeting two distinct HER2 epitopes, may represent a next-generation alternative to trastuzumab in this setting. Further phase 3 studies are anticipated.
Paper: Elimova, E., et al. Zanidatamab plus chemotherapy as first-line treatment for patients with HER2-positive advanced gastro-oesophageal adenocarcinoma: primary results of a multicentre, singlearm, phase 2 study. The Lancet. Access online here.