Givastomig Combined With Nivolumab and Chemotherapy in Adults With CLDN18.2 Positive Metastatic Gastric Cancer (GIVA-2)

Prior treatment

• Major surgery or significant injury within 4 weeks prior to first dose, or planned major surgery within 6 months.
• Radiotherapy within protocol-specified timeframes without adequate recovery.
• Active CNS metastases or carcinomatous meningitis (previously treated brain metastases allowed if stable).
• Receipt of live vaccine within 30 days or other vaccines within 7 days of first dose.

Other illness

• Second malignancy within 3 years, except certain skin or cervical cancers.
• Active or unstable gastrointestinal ulcer or bleeding within 6 weeks.
• Active autoimmune disease requiring systemic therapy within past 2 years or ongoing immunosuppressive therapy.
• Active pneumonitis or history requiring steroids/immunosuppressive therapy within 3 years.
• Significant cardiovascular disease (NYHA Class 3-4 CHF, recent MI, unstable angina, TIA/stroke, or major cardiac procedures within 6 months).
• Active or uncontrolled HIV, hepatitis B, or hepatitis C infection, or immunodeficiency (controlled infection allowed).
• Active infection requiring parenteral therapy.
• Known hypersensitivity to study drug components (e.g., DPD deficiency).

Lab values

• Any other condition or laboratory abnormality that, in the investigator's judgment, increases risk or interferes with study participation.

Other

• HER2-positive tumors.
• Participation in another therapeutic clinical trial.

• Histologically confirmed unresectable, locally advanced, or metastatic gastric, gastroesophageal junction (GEJ), or esophageal adenocarcinoma (EAC).
• Treatment-naïve for advanced/metastatic disease (prior adjuvant/neoadjuvant therapy allowed if ≥6 months since last dose).
• CLDN18.2 positive (membrane intensity score ≥1+ on ≥1% of tumor cells).
• PD-L1 positive (CPS ≥1).
• At least 1 measurable lesion per RECIST v1.1.
• ECOG performance status 0 or 1.
• Adequate organ function, including:
  • Hematologic: WBC ≥2,000/μL; ANC ≥1,500/μL; platelets ≥100,000/μL; hemoglobin ≥9 g/dL
  • Hepatic: AST/ALT ≤3×ULN (≤5×ULN if liver metastases); bilirubin ≤1.5×ULN (≤3×ULN if Gilbert's)
  • Renal: Creatinine ≤1.5×ULN or eGFR ≥50 mL/min/1.73 m²
• Life expectancy ≥90 days.
• Women of childbearing potential (WOCBP) and men must use effective contraception during the study and for a defined period after treatment.
• Willing and able to provide informed consent and comply with study procedures