The Efficacy and Safety of the Bispecific Anti-PD-1/PD-L1 Antibody IBI318 Combined with Lenvatinib in NSCLC.

Exclusion Criteria

• •Subjects who meet the following criteria cannot be selected for this study:
• •1. The pathology is small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC;
• •2. There is imaging evidence of tumor voids, tumor inclusion or invasion of large vessels. In addition, the proximity of the tumor to the large blood duct should be considered and the risk of severe bleeding associated with tumor shrinkage/necrosis after lenvatinib treatment should be excluded. (The large vessels in the chest include the main pulmonary artery, left pulmonary artery, right pulmonary artery, 4 pulmonary veins, superior vena cava, inferior vena cava and aorta);
• •3. To cohort A: subjects who have previously used anti-PD-1, PD-L1 or other immunotherapy and meet the following conditions:
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• •1. The toxicity that caused permanent discontinuation occurred before the termination of immunotherapy;
• •2. Prior to the administration of the study drug, the toxicity of the previous immunotherapy has not recovered or has not recovered to level 0-1. Asymptomatic and stable control of endocrine toxicity level 2 with appropriate replacement therapy is allowed to enter the group;
• •3. Adverse events that require additional immunosuppressive agents in addition to corticosteroids, or adverse events that still recur in the use of corticosteroids during previous immunotherapy.
• •To cohort B and C: Prior treatment: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T-cell receptor (including but not limited to CTLA-4, OX-40, CD137, etc.); Anti-pd-1, anti-PD-L1, or anti-PD-L2 drugs or drugs that target another stimulating or co-inhibiting T cell receptor (including but not limited to CTLA-4, OX-40, CD137, etc.); 4. Have received the following treatments:
• •1. Received systemic anti-tumor therapy within 2 weeks before treatment, such as chemotherapy, targeted therapy, immunotherapy (including Chinese herbal medicine with anti-tumor indications), etc.;
• •2. Previously received lenvatinib, bevacizumab, anlotinib monotherapy, or in combination with anti-PD-1 / PD-L1 drugs
• •3. Have received any investigational drug treatment within 4 weeks before treatment;
• •4. Received large doses of immunosuppressive drugs within 4 weeks before treatment (systemic glucocorticoid exceeding 10mg/day prednisone or its equivalent dose);
• •5. Received live attenuated vaccine within 4 weeks before treatment (or plan to receive live attenuated vaccine during the study period);
• •6. Have received major surgery (such as open cavity, thoracotomy, or Kaifu surgery), or unhealed surgical wounds, ulcers or fractures within 4 weeks before treatment.
• •5\. Clinically significant cardiovascular damage occurred within 12 months of the first dose of study treatment.
• •6\. Gastrointestinal diseases that may affect oral absorption of study drugs. 7. Prior gastrointestinal or grade ≥3 non-gastrointestinal fistula. 8. A history of other malignancies is known, and unless the participant has undergone potentially curative treatment, there is no evidence of disease recurrence in the 3 years since the start of that treatment.
• •9\. Severe allergy to IBI318 and lenvatinib. 10. There is clinically uncontrollable pleural effusion/abdominal effusion (subjects who do not need to drain the effusion or stop drainage for 3 days without a significant increase in effusion can be included in the group); 11. Subjects who have received thoracic radiotherapy of greater than 30 Gy within 6 months before treatment or palliative radiotherapy of 30 Gy or less within 7 days before treatment (allowing palliative treatment of bone lesions or intracranial lesions) Radiation Therapy); 12. An active autoimmune disease that requires systemic treatment (such as the use of disease-relieving drugs, glucocorticoids, or immunosuppressive agents) occurred within 2 years before the first administration. Alternative therapies (such as thyroxine, insulin, or physiological glucocorticoids for adrenal or pituitary insufficiency, etc.) are not considered systemic treatments; 13. Known allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation; 14. Before starting treatment, have not fully recovered from toxicity and/or complications caused by any intervention (ie, ≤ Grade 1 or reached baseline, excluding fatigue or hair loss); 15. Known history of human immunodeficiency virus (HIV) infection (ie HIV 1/2 antibody positive); 16. Untreated active hepatitis B (defined as HBsAg positive and the number of HBV-DNA copies detected at the same time is greater than the upper limit of the normal value of the laboratory department of the research center);
• •Note: Hepatitis B subjects who meet the following criteria can also be included in the group:
• •1. Before the first administration, the HBV viral load is less than 1000 copies/ml (200 IU/ml), and the subject should receive anti-HBV treatment during the entire study chemotherapy drug treatment to avoid viral reactivation
• •2. For subjects with anti-HBc (+), HBsAg (-), anti-HBs (-) and HBV viral load (-), there is no need to receive preventive anti-HBV treatment, but close monitoring of virus reactivation is required 17. Active HCV infected subjects (HCV antibody-positive and HCV-RNA level is higher than the lower limit of detection); 18. Live vaccines have been vaccinated within 30 days before the first administration (cycle 1, day 1); Note: It is allowed to receive inactivated virus vaccine for seasonal influenza injection within 30 days before the first administration; however, it is not allowed to receive live attenuated influenza vaccine for intranasal administration.
• •19\. Pregnant or lactating women; 20. There are any serious or uncontrollable systemic diseases, such as:
• •1. The resting electrocardiogram has major abnormalities in rhythm, conduction or morphology that are severe and difficult to control, such as complete left bundle branch block, heart block above degree II, ventricular arrhythmia or atrial fibrillation;
• •2. Left ventricular ejection fraction (LVEF) was lower than normal; 3）QTc interval is extended to more than 480 ms；
• •4\) Unstable angina pectoris, congestive heart failure, chronic heart failure of New York Heart Association (NYHA) grade ≥ 2; 5) Myocardial infarction occurred within 6 months before enrollment; 6) A history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before the first administration, or current clinically active interstitial lung disease; 7) Active tuberculosis; 8) There is an active or uncontrolled infection that requires systemic treatment; 9) There is clinically active diverticulitis, abdominal abscess, gastrointestinal obstruction; 10) Liver diseases such as liver cirrhosis, decompensated liver disease, acute or chronic active hepatitis; 11) Poor control of diabetes (fasting blood glucose (FBG)\> 10mmol/L); 12) Urine routines suggest that urine protein is ≥++, and the 24-hour urine protein quantification is confirmed to be greater than 1.0 g; 13) Subjects who have mental disorders and cannot cooperate with treatment; 21. The medical history or disease evidence, abnormal treatment or laboratory test values that may interfere with the test results, prevent the subject from participating in the study, or the investigator believes that it is not suitable for inclusion this research.