NCT07273981

Zanidatamab Combined With Chemotherapy as Neoadjuvant Therapy for HER2-high Expression G/GEJC

Phase II Clinical Study of Zanidatamab Combined With Chemotherapy as Neoadjuvant Therapy for Locally Advanced HER2-high Expression (IHC3+/2+FISH+) Gastric/Gastroesophageal Junction Adenocarcinoma

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Xijing Hospital · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

HER2 overexpression is observed in approximately 20% of gastric cancers and gastroesophageal junction (GEJ) cancers, making it a validated target for anti-tumor therapy . In advanced-stage systemic therapy, trastuzumab combined with chemotherapy has demonstrated clinical benefits for HER2-positive gastric and GEJ cancers . However, the combination of trastuzumab and pertuzumab plus chemotherapy did not significantly improve overall survival (OS) compared to trastuzumab monotherapy in HER2-expressed gastric/GEJ cancers . In neoadjuvant therapy for early-stage or locally advanced gastric cancer, there is currently no standardized perioperative regimen for HER2-positive gastric or GEJ cancers, and effective treatment remains challenging . Zanidatamab, a humanized bispecific IgG1-like antibody targeting HER2's ECD4 and ECD2 epitopes, exhibits unique enhanced functionality . Phase II studies (NCT03929666) showed that zanidatamab combined with chemotherapy as first-line therapy for HER2-positive advanced gastroesophageal adenocarcinoma (GEA) demonstrated superior survival benefits and durable responses compared to standard therapy (trastuzumab plus chemotherapy) . A Phase III study (HERIZON-GEA-01, NCT05152147) is now underway to further validate its efficacy when combined with chemotherapy ± tislelizumab versus trastuzumab-based chemotherapy . For previously untreated stage II/III locally advanced gastroesophageal junction adenocarcinoma (cT1-2N+M0, cT3-4aNanyM0) with confirmed HER2 high expression (HER2 3+/2+ FISH+), neoadjuvant zanidatamab combined with chemotherapy (FLOT/SOX/CAPOX) is being explored to evaluate safety and efficacy, potentially offering a new treatment option for HER2-positive GEJ cancers in perioperative settings .

Conditions

• Gastric/Gastroesophageal Junction Adenocarcinoma

Interventions

Type	Name	Description
DRUG	Zanidatamab Combined with Chemotherapy	Zanidatamab Combined with Chemotherapy as Neoadjuvant Therapy

Timeline

• Start date: 2026-01-01
• Primary completion: 2028-06-30
• Completion: 2029-07-31
• First posted: 2025-12-10
• Last updated: 2025-12-10