HERIZON-GEA-01 (Phase Ib/II)

Background

Phase Ib/II, N=33 (19 cohort A, 14 cohort B). First-line HER2-positive gastric/gastroesophageal junction adenocarcinoma, previously untreated, unresectable locally advanced or metastatic. Evaluated the bispecific HER2 antibody zanidatamab combined with the PD-1 inhibitor tislelizumab and CAPOX chemotherapy.

Interventions and follow up

Arm A: Zanidatamab 30 mg/kg IV Q3W + tislelizumab 200 mg IV Q3W + CAPOX
Arm B: Zanidatamab 1800/2400 mg IV Q3W (by weight) + tislelizumab + CAPOX
Primary endpoints: Confirmed ORR (cORR) and safety
Median follow up: Data through December 7, 2023

Results

Confirmed objective response rate: 75.8% (25/33)
Median duration of response: 23.3 months
Median progression-free survival: 16.7 months
Median overall survival: 32.4 months

Adverse events

Overall: Grade ≥3 treatment-related AE 66.7%; no unexpected toxicities
Gastrointestinal: diarrhea most common (100% any grade, 27.3% grade ≥3), nausea 63.6%, decreased appetite 48.5%

Conclusions

Zanidatamab plus tislelizumab and CAPOX showed clinically meaningful antitumor activity (75.8% cORR) and a manageable safety profile as first-line therapy for HER2+ gastric/GEA cancer, supporting further development in the ongoing phase III HERIZON-GEA-01 trial.

Key Limitations

Small, non-randomized phase Ib/II cohort (N=33) without a comparator arm; short follow-up; high all-grade diarrhea requires proactive management; efficacy estimates imprecise pending the randomized phase III readout.

Clinical Context

First-line HER2+ gastric/GEA standard is trastuzumab + chemotherapy + pembrolizumab (KEYNOTE-811). These early zanidatamab + tislelizumab + CAPOX data support the randomized phase III HERIZON-GEA-01, which informed an FDA priority review of tislelizumab/zanidatamab in this setting; not yet incorporated into ESMO guidance.

References