PRaG Regimens Rechallenge for Patients With Resistance to PD1/PD-L1 Inhibitors in Refractory Advanced Solid Tumors.

Inclusion Criteria:

1. Aged≥18 years;
2. The patients must conform to the advanced solid cancer with multiple metastases(may be accompanied by metastasis of other organs),progression after first-line systemic therapy and have clear pathological diagnosis report;
3. Disease progression after PD-1/PD-L1 therapy in the past, except for the permanent discontinuation of the drug due to immune-related toxicity of grade 3 or above;
4. Enrolled patients must improve the detection of PD-L1, TMB, MSI and other immune-related indicators;
5. No congestive heart failure, unstable angina pectoris, unstable arrhythmia within the past 6 months;
6. Eastern Cooperative Oncology Group (ECOG) Performance Status: 0-3, and life expectancy 3 months or more;
7. There was no history of serious hematopoietic function, abnormal heart, lung, liver, kidney function and immune deficiency;
8. One week before enrollment,absolute value of T lymphocytes≥0.5 times of normal lower limit,neutrophil ≥ 1.0×109/L,AST and ALT ≤3.0 times normal upper limit(Liver cancer/liver metastasis patients ≤5.0 times normal upper limit),creatinine ≤ 3.0 times normal upper limit,serum calcium≥2.0mmol/L;
9. Patients must have the ability to understand and voluntarily sign an informed consent form.

Exclusion Criteria:

1. Pregnant or lactating women;
2. Patients with a history of other malignant diseases in the last 2 years,except cured skin cancer and carcinoma in situ;
3. Patients with a history of uncontrolled epilepsy, central nervous system diseases or mental disorders, whose clinical severity may hinder the signing of informed consent or affect the patient's compliance with drug treatment as judged by the investigator;
4. Clinically significant (ie, active) heart disease, such as symptomatic coronary heart disease, congestive heart failure New York Heart Association (NYHA) Class II or greater, or severe arrhythmia requiring drug intervention, or a history of myocardial infarction within the last 12 months;
5. Organ transplantation requiring immunosuppressive therapy;
6. Known active infection, or significant hematological, renal, metabolic,gastrointestinal, endocrine function or metabolic disorders, or other serious uncontrolled concomitant diseases as judged by the investigator;
7. Hypersensitivity to any component of the study drug;
8. History of immunodeficiency, including positive HIV test or other acquired, congenital immunodeficiency diseases, or a history of organ transplantation, or other related diseases requiring long-term oral hormone therapy (greater than 10 mg/d prednisone);
9. Patients who are in the period of acute and chronic tuberculosis infection(patients with positive T-spot test and suspicious tuberculosis lesions on chest radiography), are in the period of acute hepatitis infection or have chronic hepatitis B virus copy number higher than the normal range;
10. Other conditions considered unsuitable by the investigator.