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

Sponsor
Zhifeng Zhao, PhD
Study ID
NCT07685704
Phase
PHASE2
Status
Not Yet Recruiting

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Conditions

  • Gastric Cancer
  • Gastroesophageal Junction Adenocarcinoma
  • HER2-positive Gastric Cancer

Eligibility Criteria

Sex
ALL
Age
18 Years - 75 Years
Healthy Volunteers
Not accepted

Interventions

  • Zanidatamab — DRUG
    Zanidatamab injection, 300 mg/vial (manufacturer: Wuxi WuXi Biologics). Administered 30 mg/kg IV Q3W. Premedication (corticosteroids, antihistamines, antipyretics) 30-60 min before infusion. First two infusions over 120-150 min; subsequent may be shortened to 60-90 min if tolerated.
  • Oxaliplatin — DRUG
    Oxaliplatin 130 mg/m2 IV infusion over \> 2 hours, D1 of each 21-day cycle. Administered after zanidatamab. Manufacturer not restricted.
  • Capecitabine — DRUG
    Capecitabine 1000 mg/m2 PO BID, D1-14 of each 21-day cycle. Alternative to S-1 as part of CAPOX backbone.
  • S-1 — DRUG
    S-1 (Tegafur, Gimeracil, Oteracil) 40 mg/m2 PO BID, D1-14 of each 21-day cycle. Alternative to capecitabine as part of SOX backbone.
  • Tislelizumab — DRUG
    Tislelizumab 200 mg Q3W IV. Alternatively, sintilimab 200 mg Q3W may be used at investigator's discretion. Conversion cohort only, for patients without immunotherapy contraindication.

Study Details

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 Dates

First listed
Jul 6, 2026
Start date
Jul 31, 2026
Status verified
Jun 2026
Primary completion
Jun 30, 2028
Completion
Dec 31, 2028

Study Design

Enrollment
46 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Neoadjuvant Cohort: Zanidatamab + Chemotherapy
    Patients with previously untreated stage III locally advanced gastric/gastroesophageal junction adenocarcinoma (cT3-4aN+M0, or cT4bNany M0 not amenable to R0 resection per MDT assessment) receive 3 cycles of zanidatamab (30 mg/kg Q3W) plus oxaliplatin-based chemotherapy (SOX: oxaliplatin 130 mg/m2 IV D1 + S-1 40 mg/m2 PO BID D1-14, Q3W; or CAPOX: oxaliplatin 130 mg/m2 IV D1 + capecitabine 1000 mg/m2 PO BID D1-14, Q3W), followed by D2 radical gastrectomy 4-6 weeks after treatment. Simon's two-stage design: n=46, H0 pCR \<= 9.6%, H1 pCR \>= 25%, one-sided alpha=0.05, power=80%.
  • Experimental: Conversion Cohort: Zanidatamab + Chemotherapy +/- PD-1 Inhibitor
    Patients with oligometastatic disease (M1, \<=2 organs, \<=5 total lesions, including liver metastases C-GCLM type I/II, retroperitoneal lymph node metastases, or other single-organ metastases) deemed potentially resectable by MDT receive zanidatamab (30 mg/kg Q3W) plus oxaliplatin-based chemotherapy, plus tislelizumab (200 mg Q3W) or sintilimab (200 mg Q3W) if no immunotherapy contraindication. Up to 8 cycles, tumor assessment every 3 cycles. Exploratory cohort; no sample size calculation.

Primary Outcome Measure

Pathological Complete Response (pCR) [ Time Frame: At the time of surgery, approximately 4-6 weeks after completion of 3 cycles of neoadjuvant treatment (each cycle is 21 days) ]

Central Contacts

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