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

Официальное название

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

Обзор

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 .

Вмешательства

• Препарат Zanidatamab Combined with Chemotherapy
  Zanidatamab Combined with Chemotherapy as Neoadjuvant Therapy

Первичные конечные точки

• Major pathological response rate (MPR) [Срок оценки: 24 months]

Вторичные конечные точки (4)

• Pathological complete response rate(pCR) [Срок оценки: 24 months]
• R0 Resection [Срок оценки: 24 months]
• Recurrence Free Survival (RFS) [Срок оценки: 5 years]
• Treatment-Emergent Adverse Events [Срок оценки: 24 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07273981 · XJ-G/GEJC-01

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗