Phase II Study of Trastuzumab Rezetecan Combined With Retlirafusp Alfa With or Without CAPOX as Perioperative Therapy for Resectable Locally Advanced Gastric/Gastroesophageal Junction Adenocarcinoma

Korábbi kezelés

• Siewert type I GEJ tumor or Siewert II tumor requiring cervicothoracic surgical approach
• Severe uncontrolled infection (≥CTCAE grade 2) within 4 weeks prior to first dose
• Systemic corticosteroid dose >10 mg prednisone equivalent within 7 days pre-treatment
• Received live attenuated vaccine within 28 days before enrollment
• Participation in other interventional clinical trials within 4 weeks prior to first dose

Más betegség

• Confirmed peritoneal metastasis, positive peritoneal cytology (CY1), or AJCC T4b disease
• History of other malignant tumor within past 5 years (excluding cured basal cell skin carcinoma, cervical/breast carcinoma in situ)
• Uncontrolled hypertension (SBP≥160 mmHg or DBP≥100 mmHg despite optimal medical management)
• GI perforation/fistula within 6 months, intestinal obstruction within 3 months (not fully resolved)
• Active severe bleeding disorder or active peptic ulcer disease
• Arterial/venous thromboembolic event within past 6 months (stroke, DVT, pulmonary embolism etc.)
• Active viral hepatitis (HBV DNA ≥2000 IU/mL; active HCV viremia) or HIV positive
• History or active interstitial lung disease, pulmonary fibrosis, active tuberculosis
• Active autoimmune disease requiring long-term systemic immunosuppressive therapy
• Hypersensitivity to any study drug or excipients
• Any medical, psychiatric or social condition judged by investigator to interfere with study compliance or subject safety

Laborértékek

• Cardiac dysfunction: NYHA grade ≥2 heart failure, LVEF <50%, unstable angina, myocardial infarction within 1 year, prolonged QTc interval (male >450ms, female >470ms), family history of sudden cardiac death <40 years old

Egyéb

• Tumor unresectable or absolute contraindication to radical gastrectomy
• Lactating female subjects

• Voluntarily sign written informed consent before any study-related procedures
• Age ≥18 and ≤75 years old
• Histopathologically confirmed gastric or gastroesophageal junction adenocarcinoma
• AJCC 8th edition stage II-III resectable disease (cT1-2N+M0, T3-4aNanyM0); negative peritoneal cytology (CY0) confirmed by pre-study laparoscopy
• HER2 expression status: High HER2 (IHC 3+ or IHC 2+ FISH-positive) OR Low/Intermediate HER2 (IHC 2+ FISH-negative / IHC 1+)
• No prior systemic anti-tumor therapy (chemotherapy, targeted therapy, immunotherapy, radiotherapy, radical gastrectomy)
• Planned radical D2 gastrectomy after neoadjuvant treatment completion
• Able to swallow oral capecitabine tablets intact
• ECOG Performance Status 0 or 1
• Estimated overall survival ≥12 months
• Adequate organ function (no blood products/G-CSF within prior 14 days):
  • ANC ≥1.5×10⁹/L; PLT ≥80×10⁹/L; Hb ≥90 g/L
  • Total bilirubin <1.5×ULN; ALT/AST ≤2.5×ULN
  • Serum Cr ≤1.5×ULN or CrCl >50 mL/min
  • INR, PT, APTT ≤1.5×ULN
• Fertile female subjects: Negative serum pregnancy test within 72 hours before first dose; all fertile participants agree to effective contraception during treatment and required post-treatment contraceptive window