Dr Elimova on Data for Zanidatamab-Based Combos by PD-L1 Status in HER2+ Gastroesophageal Adenocarcinoma

We found that both PD-L1–negative and PD-L1–positive patients benefited [with zanidatamab plus chemotherapy and tislelizumab].

Elena Elimova, MD, an associate professor and clinician investigator at the University of Toronto and Princess Margaret Hospital, discusses data from a subgroup analysis of the phase 3 HERIZON-GEA-01 trial (NCT05152147), based on PD-L1 status in patients with locally advanced or metastatic, HER2-positive gastroesophageal adenocarcinoma.

Primary data from the study showed that the experimental regimen of zanidatamab-hrii (Ziihera) in combination with chemotherapy with or without tislelizumab (Tevimbra) improved progression-free survival (PFS) compared with trastuzumab (Herceptin) plus chemotherapy. These findings supported FDA priority review of a supplemental biologics license application seeking the approval of the combination; the regulatory agency’s review is ongoing, with a target action date of August 25, 2026.

In the subgroup analysis presented at the 2026 ASCO Annual Meeting, findings showed that among patients with a PD-L1 tumor area positivity (TAP) score of at least 1% (PD-L1–positive subgroup), the median PFS was 11.3 months (95% CI, 9.6-18.5) for zanidatamab plus chemotherapy and tislelizumab (n = 187) vs 8.3 months (95% CI, 6.9-9.7) for trastuzumab plus chemotherapy (n = 188; HR, 0.65). For patients with a TAP score of less than 1% (PD-L1–negative subgroup), the median PFS was 18.5 months (95% CI, 9.7-25.2) for the experimental combination (n = 90) vs 7.9 months (95% CI, 5.8-9.6) for the control arm (n = 98; HR, 0.47). These PFS benefits were maintained in both the PD-L1–positive (HR, 0.62) and PD-L1–negative (HR, 0.48) subgroups when PD-L1 status was assessed by combined positive score (CPS).

The findings from this analysis represent a divergence from what has been observed from other studies when looking at outcomes by PD-L1 status, Elimova said, noting that the PD-L1–negative subgroup in HERIZON-GEA-01 was a large population of patients.

Additionally, she noted that although overall survival (OS) outcomes in the control arm may have been affected by increased use of subsequent therapies, OS improvements remained consistent for the experimental combination in both the PD-L1–positive (TAP, HR, 0,82; CPS, HR, 0.82) and PD-L1–negative (TAP, HR, 0.49; CPS, HR, 0.43) subgroups.