A Study of Disitamab Vedotin, Tunlametinib, and PD-1 Antibody for Advanced Gastric Cancer

Prior treatment

• Known or suspected hypersensitivity to the investigational drugs. Dysphagia. Female patients who are pregnant or breastfeeding. Patients who have received disitamab vedotin in first- or second-line treatment.
• Patients requiring systemic corticosteroids (\>10 mg/day prednisone equivalent) or other immunosuppressive medications within 14 days prior to the first dose or during the study period. However, the following circumstances are permitted for enrollment: topical or inhaled steroids, or adrenal hormone replacement therapy at a dose ≤10 mg/day prednisone equivalent, in the absence of active autoimmune disease.
• Active pulmonary tuberculosis infection identified by medical history or CT scan, or history of active pulmonary tuberculosis infection within 1 year prior to enrollment, or history of active pulmonary tuberculosis infection more than 1 year prior to enrollment without appropriate treatment.

Other illness

• Severe impairment of cardiac, pulmonary, hepatic, or renal function; hematopoietic system disorders; cachexia; or other conditions that preclude tolerability of drug therapy.
• Autoimmune diseases or history of autoimmune diseases (e.g., colitis, hepatitis, hyperthyroidism, including but not limited to these diseases or syndromes); history of immunodeficiency, including positive HIV test, or other acquired or congenital immunodeficiency diseases; history of organ transplantation or allogeneic bone marrow transplantation.
• History of interstitial lung disease or non-infectious pneumonitis.

Other

• Inability to provide informed consent due to psychological, family, social, or other factors.

• Patients with advanced gastric cancer who have received at least two lines of prior systemic therapy or are intolerant to standard therapy; HER2 immunohistochemistry (IHC) 2+ or 3+; Presence of measurable target lesions according to irRECIST criteria; Expected survival of at least 3 months; Age ≥ 18 years, male or female;
• Adequate organ function meeting the following requirements:
• White blood cell count (WBC) ≥ 3.0 × 10⁹/L, absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L;
• Platelet count ≥ 75 × 10⁹/L;
• Hemoglobin ≥ 9 g/dL;
• Serum albumin ≥ 2.8 g/dL;
• Total bilirubin ≤ 1.5 × upper limit of normal (ULN), ALT, AST, and/or ALP ≤ 2.5 × ULN;
• Serum creatinine ≤ 1.5 × ULN or creatinine clearance \> 60 mL/min; Eastern Cooperative Oncology Group (ECOG) performance status score of 0-1; Ability to understand the study and provide written informed consent.