Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; Liver function: Child-Pugh class A; Histopathologically confirmed advanced gastric cancer with HER2-positive status (HER2 2+ or 3+), which was determined by the central laboratory; Failure of or intolerance to standard first-line and second-line treatment; At least one measurable target lesion based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or at least one measurable target lesion with confirmed disease progression after local therapy; in addition, ≥ 2 measurable lesions eligible for radiotherapy, which were separate from the aforementioned target lesions; Patients with controlled hepatitis B virus (HBV) infection are eligible once they meet the following criteria: receiving anti-HBV therapy for at least 1 month before the first dose of study medication, and HBV viral load below 2000 IU/mL (10,000 copies/mL) prior to the first dose. Patients with HBV viral load < 2000 IU/mL (10,000 copies/mL), receiving ongoing anti-HBV therapy must maintain the same regimen throughout the study treatment period; Major organ function meets the following criteria within 28 days before treatment initiation: a) Hematological parameters (without blood transfusion within the preceding 14 days): Hemoglobin (HB) ≥ 80 g/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; Platelet count (PLT) ≥ 80 × 10⁹/L; b) Biochemical parameters: Total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN, or ≤ 5 × ULN in subjects with liver metastasis; Serum creatinine (Cr) ≤ 1.5 × ULN or creatinine clearance ≥ 60 mL/min; c) Coagulation parameters: International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN. For subjects on anticoagulant therapy, PT and APTT within the therapeutic range are acceptable; d) Thyroid function: Normal T3 and T4 levels; Women of childbearing potential must agree to use effective contraception during the study and for 120 days after study completion. A negative serum or urine pregnancy test is required within 7 days before study enrollment; Patients are required to offer a signed informed consent for the study.
Exclusion criteria
History of other malignant tumors within the past 5 years or concurrent, except cured basal cell carcinoma of the skin, carcinoma in situ of cervix, and papillary thyroid carcinoma; Anaphylactic reaction to RC48 (disitamab vedotin), the active ingredients of PD-1 monoclonal antibodies (sintilimab), or any excipients of the aforementioned drugs; Prior treatment with RC48, as well as prior radiotherapy to the planned targeted radiation lesion; Patients with symptoms of central nervous system metastases; Patients receiving treatment with a powerful CYP3A4 inhibitor within 1 week before enrollment, or treatment with a powerful CYP3A4 inducer within 2 weeks before enrollment; Congestive heart failure classified as New York Heart Association (NYHA) functional class III-IV; History of an ischemic cardiovascular event within 1 year before enrollment; Ongoing systemic immunosuppressive therapy; Participation in another interventional clinical trial of investigational medicinal products within 4 weeks before the first dose of study medication; Requirement for systemic corticosteroids (equivalent to > 10 mg prednisone once a day) or other immunosuppressive agents within 2 weeks before the first dose of study medication; Administration of an antitumor vaccine, or administration of a live attenuated vaccine within 4 weeks before the first dose of study medication; Patients with severe infection within 4 weeks before the first dose of study medication; Active autoimmune disease, history of autoimmune disease, or history of immunodeficiency; Active pulmonary tuberculosis, history of active pulmonary tuberculosis within 1 year before enrollment, or history of active pulmonary tuberculosis more than 1 year before enrollment without standard antituberculosis treatment; Active viral hepatitis: HBV DNA ≥ 2000 IU/mL (10,000 copies/mL); or hepatitis C virus (HCV) infection, defined as positive anti-HCV antibody and HCV-RNA above the lower limit of detection of the assay; Known history of psychotropic substance abuse, alcoholism, or illicit drug use; Pregnancy or breastfeeding women.
