Zanidatamab Combined With Chemotherapy as Neoadjuvant/Conversion Therapy for HER2-Positive (IHC 3+ or IHC 2+) Advanced Gastric or Gastroesophageal Junction Adenocarcinoma: a Phase II Open-Label Study

Starting soon · Phase 2

Conditions studied: Gastric Cancer, Gastroesophageal Junction Adenocarcinoma, HER2-positive Gastric Cancer

In brief

This is a phase II open-label study to evaluate the efficacy and safety of zanidatamab combined with chemotherapy as neoadjuvant/conversion therapy in patients with HER2-positive (IHC 3+ or IHC 2+) locally advanced or metastatic gastric/gastroesophageal junction adenocarcinoma. The study consists of two cohorts: a neoadjuvant cohort (Simon's two-stage design, n=46) for treatment-naive stage III locally advanced disease, and an exploratory conversion cohort for oligometastatic disease. Patients receive zanidatamab (30 mg/kg Q3W) plus oxaliplatin-based chemotherapy, with or without PD-1 inhibitor (tislelizumab or sintilimab). The primary endpoint is pathological complete response (pCR).

Key facts

Study ID

NCT07685704

Run by

Zhifeng Zhao, PhD

People needed

46

Starts

2026-07-01

Expected to finish

2028-12-01

Last updated by the study team

2026-07-06

Who can join

Age: 18 and older, up to 75. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Willing and able to provide written informed consent (ICF).
• Histologically and radiologically (CT/MRI) confirmed gastric or gastroesophageal junction adenocarcinoma.
• Neoadjuvant cohort: Clinical stage III (cT3-4aN+M0) or locally advanced unresectable (cT4bNany M0) assessed by MDT as not amenable to R0 resection, or technically resectable but with high-risk factors (e.g., bulky nodal fusion, invasion of critical structures).
• Conversion cohort: Not amenable to direct surgery (e.g., invasion of adjacent organs or vessels) or with distant metastases, including liver metastases (C-GCLM type I and II), confirmed retroperitoneal lymph node metastases, or other single-organ metastases.
• HER2-positive by IHC (3+; or 2+ with FISH testing). No time window restriction on FISH.
• Age 18-75 years, male or female.
• ECOG performance status 0-1; no contraindication to surgery.
• Adequate organ function for successful abdominal surgery.
• Life expectancy >= 3 months.
• Laboratory parameters within 7 days before enrollment:
• WBC > 4.0 x 10\^9/L and < 15 x 10\^9/L; ANC > 1.5 x 10\^9/L; Hb >= 90 g/L; PLT >= 100 x 10\^9/L.
• Total bilirubin <= 1.5 x ULN; AST and ALT <= 2.5 x ULN.
• Creatinine <= 1.5 x ULN, or CrCl > 60 mL/min (Cockcroft-Gault).
• No anticoagulation: INR and aPTT <= 1.5 x ULN. On stable anticoagulation: maintain stable dose.
• Good compliance; able to complete protocol-specified examinations and specimen collection.
• Female patients of childbearing potential must agree to contraception from ICF signing through at least 5 months after last dose and refrain from breastfeeding. Male patients must agree to contraception from first dose through at least 7 months after last dose.

You may not qualify if…

• Synchronous or metachronous malignancies of other organs, or recurrent disease.
• Prior systemic therapy for gastric cancer (neoadjuvant cohort).
• History of malignancy within 5 years before screening, except those with > 90% 5-year overall survival.
• Significant cardiopulmonary dysfunction.
• Major surgery within 4 weeks before study treatment initiation, or anticipated major surgery during study period (excluding diagnostic procedures).
• Severe infection within 4 weeks before study treatment initiation.
• Prior chemotherapy or molecular targeted therapy (neoadjuvant cohort).
• Known hypersensitivity to study drugs or excipients, or history of severe allergic reactions to monoclonal antibodies.
• Factors affecting oral medication intake (e.g., dysphagia >= grade 2, chronic diarrhea).
• Significant uncontrolled comorbidities that may affect protocol compliance or interpretation of outcomes.
• Pregnancy or breastfeeding, or planning pregnancy during the study.
• Diagnosis of immunodeficiency or receiving systemic corticosteroid (> 10 mg/day prednisone equivalent) or other immunosuppressive therapy within 2 weeks before first dose.
• Active hepatitis B (HBV DNA >= 1 x 10\^3 copies/mL or >= 200 IU/mL), positive anti-HCV, or positive HIV.
• Participation in another anti-tumor clinical trial within 28 days before first dose.
• Any condition that in the investigator's judgment may lead to premature study termination (e.g., serious illness including psychiatric disorders requiring concomitant treatment, severe laboratory abnormalities, family/social factors affecting subject safety or data collection).
• Patient or family refusal to sign informed consent.

Where it is running

• Xijing Hospital, Air Force Medical University — Xi'an, Shaanxi, China

Full record on ClinicalTrials.gov

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