PD-1 Antibody Carilizumab Combined with Apatinib for Unresectable Stage III and IV DMMR Gastric Cancer

1. Age greater than or equal to 18 years old, gender not limited;
2. Histologically confirmed unresectable stage III and IV dMMR (complete loss of at least one protein, MLH1, PMS2, MSH2, and MSH6), gastric adenocarcinoma (GC) (excluding neuroendocrine tumors) or gastroesophageal junction adenocarcinoma (GEJ);
3. Unresectable gastric cancer patients with potential for conversion therapy, defined as gastric cancer patients with single organ metastasis (such as liver metastasis, ovarian metastasis, lung metastasis), retroperitoneal lymph node metastasis, supraclavicular lymph node metastasis, localized peritoneal metastasis, invasion of surrounding organs, and other gastric cancer patients evaluated by researchers as feasible for conversion therapy;
4. Without surgery, radiation therapy, or immunotherapy for the gastric cancer lesion or metastatic tumor.
5. ECOG PS score 0-1 points;
6. Expected survival period ≥ 3 months;
7. The main organ functions are normal, and there are no severe abnormalities in blood, heart, lung, liver, kidney, bone marrow, or immunodeficiency diseases.
8. Normal coagulation function, no active bleeding or thrombotic diseases:
9. The time from the end of traditional Chinese medicine, traditional Chinese patent medicines and simple preparations and immunomodulator (such as thymosin, interleukin, etc.) that have used anti-tumor drugs in the past to the start of the study must be ≥ 2 weeks;
10. Non surgical sterilization or female subjects of childbearing age are required to use a medically approved contraceptive measure (such as intrauterine device, contraceptive pill, or condom) during the study treatment period and within 180 days after the end of the study treatment; Female subjects of childbearing age who undergo non-surgical sterilization must have a negative serum HCG test within 72 hours prior to randomization; And it must be during non lactation period; For male participants whose partners are women of childbearing age, effective contraception methods should be used during the study treatment period and within 180 days after the end of the study treatment period.
11. Subjects voluntarily participated in this study, fully understood and informed of the study, and signed the Informed Consent Form (ICF);

Exclusion Criteria:

1. Other malignant tumors have been diagnosed within 5 years before the first use of the investigational drug, except for effectively treated skin basal cell carcinoma, skin squamous cell carcinoma and/or effectively resected cervical carcinoma in situ and/or breast cancer and/or thyroid cancer and other malignant tumors that have achieved long-term survival;
2. Suffering from any active autoimmune disease or history of autoimmune disease, such as interstitial pneumonia, uveitis, enteritis, hepatitis, pituitary inflammation, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism (except for patients with stable hormone levels after treatment); Subjects with childhood asthma who have been completely relieved and do not require any intervention or vitiligo in adulthood may be included, but those who require medical intervention with bronchodilators may not be included;
3. People with congenital or acquired immune deficiency, such as people infected with human immunodeficiency virus (HIV), active hepatitis B (HBV DNA ≥ 500 IU/ml), hepatitis C (hepatitis C antibody is positive, and HCV-RNA is higher than the detection limit of the analytical method) or people with co infection of hepatitis B and hepatitis C;
4. Within 14 days prior to the first use of the investigational drug, immunosuppressive drugs have been used, excluding nasal and inhaled corticosteroids or systemic corticosteroids at physiological doses (i.e. not exceeding 10 mg/day of prednisolone or other corticosteroids at physiological doses of equivalent drugs);
5. Vaccination with attenuated live vaccine within 4 weeks before the first administration or planned during the study period;
6. Patients with hypertension who cannot be reduced to normal range by antihypertensive medication (systolic blood pressure ≤ 140 mmHg/diastolic blood pressure ≤ 90 mmHg);
7. Suffering from uncontrolled clinical symptoms or diseases of the heart, such as (1) NYHA class II or above heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, (4) poorly controlled arrhythmia;
8. Patients who have had or currently have interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, etc., and whose lung function is severely impaired, which may interfere with the detection and management of suspected drug-related pulmonary toxicity;
9. suffer from active pulmonary tuberculosis;
10. Severe infection (such as requiring intravenous infusion of antibiotics, antifungal or antiviral drugs) within 4 weeks before the first medication, or unexplained fever (body temperature ≥ 38.5 ° C) during the screening period/before the first administration;
11. Known history of allogeneic organ transplantation or allogeneic hematopoietic stem cell transplantation;
12. Those who are known to have a history of allergies to the components of this drug regimen;
13. There is a possibility of increasing participation in research and medication risks, or other severe, acute, and chronic diseases