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
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 30
- 主要终点
- Major pathological response rate (MPR)
研究概览
简要总结
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 .
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
Experimental: Zanidatamab Combined with Chemotherapy
干预措施: Zanidatamab Combined with Chemotherapy (Drug)
结局指标
主要结局
Major pathological response rate (MPR)
时间窗: 24 months
MPR is defined as 10% or fewer viable cancer cells from the resected tumor following neoadjuvant treatment
次要结局
- Pathological complete response rate(pCR)(24 months)
- Treatment-Emergent Adverse Events(24 months)
- R0 Resection(24 months)
- Recurrence Free Survival (RFS)(5 years)