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HERIZON-GEA-01

A Study of Zanidatamab in Combination With Chemotherapy Plus or Minus Tislelizumab in Patients With HER2-positive Advanced or Metastatic Gastric and Esophageal Cancers

Phase 3NCT05152147

Population
Previously untreated, centrally confirmed HER2-positive advanced gastroesophageal adenocarcinoma.
Design
Open-label randomised phase 3 trial: patients were randomly assigned 1:1:1 to zanidatamab and tislelizumab plus chemotherapy, zanidatamab plus chemotherapy, or trastuzumab plus chemotherapy. Two primary endpoints: progression-free survival and overall survival. Median follow-up 25.9 months; the overall survival results are an interim analysis.
Primary endpoint
PFS, OS
Arms
  • Trastuzumab plus chemotherapy (control, n = 308): Trastuzumab plus chemotherapy
  • Zanidatamab plus chemotherapy (experimental, n = 304): Zanidatamab plus chemotherapy
  • Zanidatamab, tislelizumab and chemotherapy (experimental, n = 302): Zanidatamab and tislelizumab plus chemotherapy
People
Shitara K, HERIZON-GEA-01 Investigators
PFSHR 0.63 (95% CI 0.51–0.78)Δ median PFS+4.3 monthsPFSHR 0.65 (95% CI 0.52–0.81)Δ median PFS+4.3 monthsOSHR 0.72 (95% CI 0.57–0.90)Δ median OS+7.2 months
Show the numbers
Results reported for HERIZON-GEA-01
EndpointAnalysisZanidatamab plus chemotherapy / Zanidatamab, tislelizumab and chemotherapyTrastuzumab plus chemotherapyEffect
PFSRandomised patients in the two arms compared (302 vs 308)primaryShitara 2026median 12.4 monthsmedian 8.1 monthsHR 0.63 (95% CI 0.51–0.78)P<0.001Median follow-up 25.9 months. The abstract does not label the progression-free survival analysis as interim; only the overall survival analysis is called interim.
PFSRandomised patients in the two arms compared (304 vs 308)primaryShitara 2026median 12.4 monthsmedian 8.1 monthsHR 0.65 (95% CI 0.52–0.81)P<0.001Median follow-up 25.9 months. The abstract does not label the progression-free survival analysis as interim; only the overall survival analysis is called interim.
OSRandomised patients in the two arms compared (302 vs 308)interimShitara 2026median 26.4 monthsmedian 19.2 monthsHR 0.72 (95% CI 0.57–0.90)P=0.004Interim analysis.
OSRandomised patients in the two arms compared (304 vs 308)interimShitara 2026median 24.4 monthsmedian 19.2 monthsHR 0.80 (95% CI 0.64–1.01)P=0.06Interim analysis; the abstract states overall survival did not differ significantly between zanidatamab plus chemotherapy and trastuzumab plus chemotherapy at this analysis. The 19.2-month control median is the one the abstract gives for the triplet comparison against the same control arm.
Results reported for HERIZON-GEA-01
EndpointAnalysisZanidatamab plus chemotherapy / Zanidatamab, tislelizumab and chemotherapyTrastuzumab plus chemotherapyEffect
PFSRandomised patients in the two arms compared (302 vs 308)primaryShitara 2026median 12.4 monthsmedian 8.1 monthsHR 0.63 (95% CI 0.51–0.78)P<0.001Median follow-up 25.9 months. The abstract does not label the progression-free survival analysis as interim; only the overall survival analysis is called interim.
PFSRandomised patients in the two arms compared (304 vs 308)primaryShitara 2026median 12.4 monthsmedian 8.1 monthsHR 0.65 (95% CI 0.52–0.81)P<0.001Median follow-up 25.9 months. The abstract does not label the progression-free survival analysis as interim; only the overall survival analysis is called interim.
OSRandomised patients in the two arms compared (302 vs 308)interimShitara 2026median 26.4 monthsmedian 19.2 monthsHR 0.72 (95% CI 0.57–0.90)P=0.004Interim analysis.
OSRandomised patients in the two arms compared (304 vs 308)interimShitara 2026median 24.4 monthsmedian 19.2 monthsHR 0.80 (95% CI 0.64–1.01)P=0.06Interim analysis; the abstract states overall survival did not differ significantly between zanidatamab plus chemotherapy and trastuzumab plus chemotherapy at this analysis. The 19.2-month control median is the one the abstract gives for the triplet comparison against the same control arm.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.630.51–0.78
PFS0.650.52–0.81
OS0.720.57–0.9
OS0.80.64–1.01
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Zanidatamab, tislelizumab and chemotherapy (experimental)
  • Trastuzumab plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZanidatamab, tislelizumab and chemotherapyTrastuzumab plus chemotherapy
0100.0%100.0%
863.9%50.4%
1640.9%25.4%
2327.6%14.0%
3117.7%7.0%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%051015202530Months (modelled)
  • Zanidatamab plus chemotherapy (experimental)
  • Trastuzumab plus chemotherapy (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsZanidatamab plus chemotherapyTrastuzumab plus chemotherapy
0100.0%100.0%
863.9%50.4%
1640.9%25.4%
2327.6%14.0%
3117.7%7.0%
Primary publication: Shitara K, Elimova E, Liu T, Tabernero J, Lee KW, Schenker M, et al. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer. N Engl J Med. 2026;394(20):2002-2014. PubMedDOI

Appears in

Sources

  1. Shitara K, Elimova E, Liu T, Tabernero J, Lee KW, Schenker M, et al. Zanidatamab with and without Tislelizumab in HER2-Positive Gastroesophageal Cancer. N Engl J Med. 2026;394(20):2002-2014.

    PubMedDOI