First Line Sintilimab Combined With Anlotinib and Platinum Doublet Chemotherapy in Malignant Pleural Mesothelioma

Exclusion Criteria

• •Diagnosis of malignant diseases other than malignant pleural mesothelioma (excluding radical skin basal cell carcinoma, skin squamous cell carcinoma, and / or radical resection of carcinoma in situ) within 5 years before the first administration
• •Currently participating in interventional clinical research treatment, or receiving other research drugs or using research instruments within 4 weeks before the first administration;
• •Previous usage of the following treatments: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs, for another stimulating or synergistic inhibition of T cell receptors (for example, CTLA-4, OX-40, CD137) drug;
• •Within 2 weeks before the first administration, they received systemic systemic therapy with anti-tumor indications of proprietary Chinese medicine or immunomodulatory drugs (including thymosin, interferon, interleukin, except for controlling local use of pleural effusion)
• •Active autoimmune diseases requiring systemic treatment (such as the use of disease-relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration. Alternative therapy (such as thyroxine, insulin or physiological glucocorticoids for adrenal or pituitary insufficiency) are not considered systemic therapy.
• •The patients are received systemic glucocorticoid therapy (excluding nasal, inhaled or other topical glucocorticoids) or any other form of immunosuppressive therapy within 7 days before the first administration.
• •Note: The use of physiological doses of glucocorticoids (≤10 mg/day prednisone or equivalent drugs) is allowed;
• •There are clinically uncontrollable pleural effusion / ascites (patients who do not need drainage or stop drainage for 3 days without a significant increase in effusion can be enrolled in the group)
• •Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• •Those who are known to be allergic to the active ingredients or excipients of Sintilimab in this study.
• •Patients with multiple factors affecting oral drugs (such as inability to swallow, gastrointestinal resection, chronic diarrhea and intestinal obstruction, etc.)
• •Symptomatic or uncontrolled brain metastasis;
• •Active hemoptysis (at least 2.5ml or 1/2 teaspoon of blood was spit out at a time) 3 months before the first study drug administration;
• •Imaging showed that there were tumors invading / infiltrating large blood vessels or bleeding tendency assessed by researchers or radiologists;
• •Received major surgery (except for surgery for the purpose of biopsy) within 4 weeks before the first study drug administration, or is expected to undergo major surgery during the study period;
• •Severe unhealed wound ulcers or fractures;
• •Minor surgery was performed within 48 hours before first receiving the study drug (outpatient / inpatient surgery requiring local anesthesia, including central venous catheterization);
• •Use aspirin (\>325 mg/day) or other non-steroidal anti-inflammatory drugs that are known to inhibit platelet function for 10 consecutive days (within 10 days before receiving the first dose of study drug) at present or in the near future;
• •Current or recent treatment with full-dose oral or parenteral anticoagulants or thrombolytic agents for 10 consecutive days (within 10 days before receiving the first study drug) Note: Prophylactic use of low-dose anticoagulants is permitted: low-dose warfarin (≤ 1mg/d) is allowed for preventive purposes on the premise that the international standardized ratio of prothrombin time (INR) ≤ 1.5. Low-dose heparin (≤ 12000 U/e d) or low-dose aspirin (≤ 100mg/d).
• •Hereditary bleeding tendency or coagulation dysfunction, or history of thrombosis;
• •Did not fully recover from toxicity and / or complications caused by any intervention (i.e., ≤ level 1 or reached baseline, excluding fatigue or hair loss) before starting treatment;
• •Known human immunodeficiency virus (HIV) infection history (i.e. HIV 1/2 antibody positive)
• •Untreated active hepatitis B (defined as HBsAg positive and the number of HBV-DNA copies detected is greater than the upper limit of the normal value of the laboratory in the research center).
• •Note: hepatitis B subjects who meet the following criteria can also be enrolled in the group:
• •1. Before the first administration, the HBV viral load is less than 1000 copies/ml (200 IU/ml), and the patients should receive anti-HBV treatment during the entire study drug treatment period to avoid viral reactivation;
• •2. For patients with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is no need to receive preventive anti-HBV therapy. However, the virus needs to be closely monitored for reactivation
• •* Active HCV infection subjects (HCV antibody positive and HCV-RNA level higher than the lower limit of detection)
• •* Live vaccine is given within 30 days before the first administration (cycle 1, day 1).
• •Note: It is allowed to receive inactivated virus vaccine for seasonal influenza within 30 days before the first administration; however, it is not allowed to receive live attenuated influenza vaccine for intranasal administration..
• •Pregnant or lactating women;
• •There are any serious or uncontrollable systemic diseases, such as
• •1. significant abnormalities in rhythm, conduction, or morphology of resting electrocardiogram and serious and uncontrollable symptoms, such as complete left bundle branch block, second-degree cardiac block, ventricular arrhythmia or atrial fibrillation.
• •2. unstable angina pectoris, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) grade ≥ 2;
• •3. any arterial thrombosis, embolism or ischemia occurred within 6 months before treatment, such as myocardial infarction, unstable angina pectoris, cerebrovascular accident or transient ischemic attack;
• •4. Blood pressure control is not satisfactory (systolic blood pressure \> 140mmHg, diastolic blood pressure \> 90mmHg).
• •5. within 1 year before the first administration, there is a history of non-infectious pneumonia requiring glucocorticoid treatment, or currently there is clinically active interstitial lung disease;
• •6. active pulmonary tuberculosis;
• •7. active or uncontrolled infections requiring systemic treatment;
• •8. clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction.
• •9. liver diseases such as liver cirrhosis, decompensated liver disease, acute or chronic active hepatitis;
• •10. poorly controlled diabetes (fasting blood glucose (FBG) \> 10mmol/L);
• •11. patients with urinary protein ≥ + + and confirmed 24-hour urinary protein quantity \> 1.0g;
• •12. patients with mental disorders and unable to cooperate with treatment
• •At the discretion of the investigator, there are patients with serious concomitant disease that compromises patient safety or affects the patient's completion of the study; The investigator believes that there are other potential risks and is not suitable for participation this research.