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

NCT07273981 | Not Yet Recruiting Phase 2

• 1 other identifier: XJ-G/GEJC-01
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief 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

Outcome Measures

Primary Outcomes (1)

• Major pathological response rate (MPR)

  MPR is defined as 10% or fewer viable cancer cells from the resected tumor following neoadjuvant treatment

  24 months

Secondary Outcomes (4)

• Pathological complete response rate(pCR)

  24 months

• R0 Resection

  24 months

• Recurrence Free Survival (RFS)

  5 years

• Treatment-Emergent Adverse Events

  24 months

Study Arms (1)

Experimental: Zanidatamab Combined with Chemotherapy

EXPERIMENTAL

Drug: Zanidatamab Combined with Chemotherapy

Interventions

Zanidatamab Combined with Chemotherapy DRUG

Zanidatamab Combined with Chemotherapy as Neoadjuvant Therapy

Experimental: Zanidatamab Combined with Chemotherapy

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Histologically/radiologically confirmed Stage II/III (cT1-2N+M0 or cT3-4aNanyM0) Siewert II/III GEJ/gastric adenocarcinoma.
• HER2-high (IHC 3+/2+FISH+); HER2 2+ requires FISH (no time restriction).
• Age 18-75, any gender.
• ECOG 0-1, surgically eligible.
• Adequate organ function for abdominal surgery.
• Life expectancy ≥3 months.

You may not qualify if:

• Unresectable/metastatic (Stage IV) disease.
• Prior systemic GC therapy.
• Other malignancies within 5 years (except those with \>90% 5-year survival).
• Cardiopulmonary dysfunction.
• Major surgery within 4 weeks pre-study.
• Severe infection within 4 weeks.
• Prior chemo/targeted therapy.
• Hypersensitivity to study drugs/excipients/mAbs.
• Factors impairing oral intake (e.g., ≥Grade 2 dysphagia/chronic diarrhea).
• Uncontrolled comorbidities affecting compliance/outcomes.
• Pregnancy/lactation/planned pregnancy.
• Immunosuppression (\>10mg/day prednisone equivalent within 2 weeks).
• Active HBV (DNA ≥1×10³ copies/mL or ≥200IU/mL), HCV+, or HIV+.
• Other antitumor trials within 28 days.
• Other high-risk conditions (e.g., psychiatric disorders) per investigator.

Sponsors & Collaborators

• Xijing Hospital: lead

MeSH Terms

Interventions

Drug Therapy

Intervention Hierarchy (Ancestors)

Therapeutics

Central Study Contacts

Xiaohua Li

CONTACT

+8619991901686; xįyylixiaohua@163.com

Pengfei Yu

CONTACT

+8615249254020; yupengfei8989@163.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2025
• First Posted: December 10, 2025
• Study Start: January 1, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): July 31, 2029
• Last Updated: December 10, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share