1L HER2+ GEA trial design
HERIZON-GEA-01: The largest global, randomized, open-label, phase 3 trial that assessed outcomes in patients with 1L HER2+ unresectable locally advanced or metastatic GEA, regardless of PD-L1 status1-4
Key eligibility criteria
- Age ≥18 years
- Unresectable, locally advanced, recurrent or metastatic GEA (GC, GEJC, EAC)
- HER2 IHC 3+ staining or IHC 2+ staining/ISH-positivity per central testing
- ECOG PS 0 or 1
- No prior treatment for locally advanced or metastatic disease
- No prior HER2-targeted agents or immunotherapy in any setting
Stratification factors
- Geographic region (Asia, EU/North America, rest of world)
- HER2 status (IHC 3+ staining, IHC 2+ staining with ISH positivity)
- ECOG PS (0 or 1)
R
1:1:1
(N=914)
TEVIMBRA* + zanidatamab-hrii† +
chemotherapy‡
IV Q3W (n=302)
Mandatory prophylaxis
for infusion-related reactions
and diarrhea
Trastuzumab + chemotherapy
IV Q3W (n=308)
Zanidatamab-hrii + chemotherapy
IV Q3W (n=304)
Mandatory prophylaxis
for infusion-related reactions
and diarrhea
Patients in the zanidatamab-containing arms received mandatory prophylaxis for infusion-related reactions (glucocorticoids, antihistamines, and acetaminophen administered 30 to 60 minutes before infusion) and diarrhea (loperamide administered orally at 4 mg twice daily for the first 7 days of Cycle 1)
Treatment regimens continued until disease progression, death, or unacceptable toxicity.§ Chemotherapy could be discontinued after 6 cycles
Key endpoints
Dual primary endpoints:
- OS
- PFS (per BICR)
Secondary endpoints:
- ORR and DoR
- Frequency and severity of AEs
HERIZON-GEA-01 enrolled a broad range of patients4
Frequently Asked Questions
How was TEVIMBRA studied in 1L HER2+ advanced GEA?
HERIZON-GEA-01 began enrollment in December 2021. At the time of approval, HERIZON-GEA-01 was the largest clinical trial of its kind in this setting.1-4
*TEVIMBRA 200 mg was administered.1
†Zanidatamab-hrii 1800 mg (<70 kg)/2400 mg (≥70 kg) was administered.1
‡Physician’s choice of capecitabine plus oxaliplatin or 5-fluorouracil plus cisplatin. Chemotherapy was administered for at least 6 cycles or until disease progression, unacceptable toxicity, or another criterion for treatment discontinuation was met.1,4
§CT/MRI scans were performed every 6 weeks for the first 54 weeks, then every 9 weeks.4
‖Other races include Black, American Indian, Alaska Native, other, multiple, not reported, or unknown.4
1L, first line; AE, adverse event; BICR; Blinded Independent Central Review; CT, computed tomography; DoR; duration of response; EAC, esophageal adenocarcinoma; ECOG, Eastern Cooperative Oncology Group; GC, gastric cancer; GEA, gastroesophageal adenocarcinoma; GEJC, gastroesophageal junction cancer; HER2, human epidermal growth factor receptor 2; IHC, immunohistochemistry; ISH, in situ hybridization; IV, intravenous; MRI, magnetic resonance imaging; ORR, overall response rate; OS, overall survival; PD-1, programmed death receptor 1; PD-L1, programmed death ligand 1; PFS, progression-free survival; PS, performance status; Q3W, every 3 weeks; R, randomization; TAP, tumor area positivity.
References: 1. TEVIMBRA. Prescribing Information. BeOne Medicines USA, Inc.; 2026. 2. Bang YJ, Van Cutsem E, Feyereislova A, et al. Lancet. 2010;376(9742):687-697. doi:10.1016/S0140-6736(10)61121-X 3. Keytruda. Prescribing Information. Merck & Co. Inc.; 2026. 4. Shitara K, Elimova E, Liu T, et al. N Engl J Med. 2026;394(20):2002-2014. doi:10.1056/NEJMoa2517729 5. Ziihera. Prescribing Information. Jazz Pharmaceuticals, Inc.; 2026.