BeOne’s ZIIHERA/Tislelizumab Combo Delivers 26.4-Month Median OS in Phase 3 Trial

The HERIZON-GEA-01 trial compared zanidatamab plus chemotherapy with and without tislelizumab against trastuzumab plus chemotherapy in first-line advanced HER2-positive gastroesophageal adenocarcinoma. The triplet regimen achieved a median overall survival of 26.4 months and the doublet 24.4 months versus 19.2 months for the control, with both zanidatamab arms showing median progression-free survival of 12.4 months and durations of response of 20.7 and 14.3 months compared with 8.3 months in the control arm.

Subgroup analysis revealed consistent benefit regardless of PD-L1 status. In PD-L1-negative patients, the triplet regimen delivered a median OS of 29.7 months versus 15.8 months in the control, and in PD-L1-positive patients 26.4 months versus 21.2 months, with corresponding 18-month PFS rates of 50.3% and 42.6%.

The safety profile of the zanidatamab/tislelizumab triplet was manageable, with Grade ≥3 diarrhea in 24.5% of patients versus 20.0% in the doublet and 12.9% in the control arm. No new safety signals emerged, anti-diarrheal prophylaxis was implemented in cycle 1, and discontinuation due to diarrhea remained below 5%.

The U.S. FDA has granted priority review to the supplemental BLA for tislelizumab, while China’s NMPA has accepted sBLAs for both zanidatamab and tislelizumab for first-line advanced/metastatic HER2+ GEA. BeOne holds regional rights in Asia (excluding India and Japan), Australia and New Zealand and plans to expedite regulatory submissions in these markets.