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NCT Number: NCT07273981

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

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 .

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Key information

Conditions

Gastric/Gastroesophageal Junction Adenocarcinoma

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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.

Exclusion criteria

Exclusion criteria

  • 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.
  • Refusal to sign consent.

Treatment and study plan

Zanidatamab Combined with Chemotherapy

Drug

Zanidatamab Combined with Chemotherapy as Neoadjuvant Therapy

Primary outcomes

  1. Major pathological response rate (MPR)

    Time frame: 24 months

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

Secondary outcomes

  1. Pathological complete response rate(pCR)

    Time frame: 24 months

  2. R0 Resection

    Time frame: 24 months

  3. Recurrence Free Survival (RFS)

    Time frame: 5 years

  4. Treatment-Emergent Adverse Events

    Time frame: 24 months

Study contacts

Contact information is provided by the study sponsor or research team.

Pengfei Yu

CONTACT

[email protected]

+8615249254020

Xiaohua Li

CONTACT

xį[email protected]

+8619991901686

Sponsors and collaborators

Lead sponsor

Xijing Hospital

Other

Registry information

Official study title

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

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Dec 10, 2025
Registry last updated
Dec 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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