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

Korábbi kezelés

• Prior systemic therapy for gastric cancer (neoadjuvant cohort).
• 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).
• Factors affecting oral medication intake (e.g., dysphagia \>= grade 2, chronic diarrhea).
• Diagnosis of immunodeficiency or receiving systemic corticosteroid (\> 10 mg/day prednisone equivalent) or other immunosuppressive therapy within 2 weeks before first dose.
• Participation in another anti-tumor clinical trial within 28 days before first dose.

Más betegség

• Synchronous or metachronous malignancies of other organs, or recurrent disease.
• History of malignancy within 5 years before screening, except those with \> 90% 5-year overall survival.
• Known hypersensitivity to study drugs or excipients, or history of severe allergic reactions to monoclonal antibodies.
• Active hepatitis B (HBV DNA \>= 1 x 10\^3 copies/mL or \>= 200 IU/mL), positive anti-HCV, or positive HIV.

Laborértékek

• 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).

Egyéb

• Significant cardiopulmonary dysfunction.
• Significant uncontrolled comorbidities that may affect protocol compliance or interpretation of outcomes.
• Pregnancy or breastfeeding, or planning pregnancy during the study.
• Patient or family refusal to sign informed consent.

• 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.