NEJM Paper Shows Zanidatamab Triplet Extends Survival Over Trastuzumab in First‑Line HER2+ Gastroesophageal Cancer

The peer‑reviewed results could reshape first‑line care as sponsors pursue U.S. and Chinese approvals and present PD‑L1 subgroup data at ASCO next week.

Overview

The New England Journal of Medicine published Phase 3 HERIZON‑GEA‑01 results on Wednesday showing zanidatamab plus tislelizumab and chemotherapy produced a median overall survival of 26.4 months versus 19.2 months for trastuzumab plus chemotherapy.
Both zanidatamab regimens significantly improved progression‑free survival with a median PFS of 12.4 months compared with 8.1 months for the control arm.
Prespecified subgroup analyses to be presented at ASCO on June 1 show the triplet’s survival benefit held across PD‑L1 groups, including patients with PD‑L1 TAP <1% where median OS was 29.7 versus 15.8 months with the control therapy.
Safety was consistent with known HER2‑directed and PD‑1 inhibitor effects; Grade 3 or higher diarrhea was more common in the triplet arm and prompted mandatory anti‑diarrheal prophylaxis during the first cycle.
Regulatory action is under way with the FDA accepting a supplemental filing for tislelizumab with priority review and China’s CDE accepting sBLAs for both agents, while sponsors plan guideline submissions and a second interim OS readout is expected in mid‑2026.