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NCT07273981Not yet recruitingPhase 2

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

Source: ClinicalTrials.gov · Last updated 10 Dec 2025

Brief summary (registry, in English)

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 .

Status (registry)
Not yet recruiting
Phase (registry)
Phase 2
Study type
Interventional
Enrollment
30 (estimated)
First submitted
26 Nov 2025
Start date
1 Jan 2026
Primary completion date
30 Jun 2028
Lead sponsor
Xijing Hospital
NCT number
NCT07273981

What you commit to

  • Study type: Interventional · Phase 2
  • Planned participants: 30
  • From 1 Jan 2026 to the primary completion date, 30 Jun 2028
  • No sites listed in no country
  • Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

  • Prior systemic GC therapy.
  • Major surgery within 4 weeks pre-study.
  • Prior chemo/targeted therapy.

Other illness

  • Unresectable/metastatic (Stage IV) disease.
  • Other malignancies within 5 years (except those with \>90% 5-year survival).
  • Severe infection within 4 weeks.
  • Hypersensitivity to study drugs/excipients/mAbs.
  • Other high-risk conditions (e.g., psychiatric disorders) per investigator.

Lab values

  • Active HBV (DNA ≥1×10³ copies/mL or ≥200IU/mL), HCV+, or HIV+.

Other

  • Cardiopulmonary dysfunction.
  • 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).
  • Other antitumor trials within 28 days.
  • Refusal to sign consent.

Who the study is looking for

  • 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.

Age in the registry: 18 years to 75 years · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

This page is information, not medical advice. Discuss any trial with your doctor.