QL1706 plus chemotherapy for immune-resistant advanced NSCLC

Inclusion Criteria:

* Voluntarily participate in the research and sign an informed consent form; Age ≥ 18 years old, ≤ 75 years old;
* Diagnosed with NSCLC through histology or cytology;
* No EGFR sensitive mutations or ALK gene translocation changes;
* Previously received PD-1/PD-L1 inhibitors combined with platinum based dual therapy or sequential therapy as first-line treatment for advanced metastatic or recurrent NSCLC, and disease progression occurred during or after treatment; At least one measurable lesion should be used as the target lesion (RECIST v1.1 standard);
* ECOG score: 0-2 points;
* Expected survival period is not less than 12 weeks;
* Women of childbearing age must undergo a pregnancy test (serum or urine) with a negative result within 28 days before enrollment, and voluntarily use appropriate contraception methods during the observation period and within 8 weeks after the last dose; For males, surgical sterilization or consent to use appropriate contraception methods during the observation period and within 8 weeks after the last dose should be provided;
* The laboratory test results during the screening period indicate that the patient has good organ function: a) Hematology (no blood transfusion within 14 days and no treatment with blood components or granulocyte colony-factor): Neutrophil count (NEU) ≥ 1.5 × 10 \^ 9/L (1500/mm3); Platelet count (PLT) ≥ 100 × 10 \^ 9/L (100000/mm3); Hemoglobin ≥ 90 g/L; b) Liver: serum total bilirubin (TBil) ≤ ULN; Glutamate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 1.5 × ULN; AST or ALT should be 1.5-3.5 × ULN, and alkaline phosphatase (ALP) should be ≤ 2.5 × ULN; c) Kidney: creatinine clearance rate (CrCl) calculated value ≥ 30 mL/min; d) Coagulation function: International normalized ratio (INR) ≤ 1.5, and prothrombin time (PT) or activated partial thromboplastin time (APTT) ≤ 1.5 × ULN; j) International Normalized Ratio (INR) ≤ 1.5; Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN;
* Patients whom researchers believe can benefit.

Exclusion Criteria:

* There are EGFR sensitive mutations or ALK gene translocation changes present;
* Previously received PD1/CTLA4 bispecific antibody therapy;
* Adverse reactions caused by previous treatment have not recovered to CTCAE (version 5.0) grade 1 or below (excluding toxicity ≤ grade 2 that has been determined by the researcher to exist for a long time, cannot be recovered, and does not increase safety risks);
* Symptomatic central nervous system metastasis. Patients who have received treatment for brain metastases and have been deemed stable by researchers may consider participating in this study;
* For patients with poor control of cancer-related pain, those who require analgesic treatment must receive a stable dose of treatment before participating in the study;
* Chest fluid, ascites or pericardial effusion with clinical symptoms or unstable condition after symptomatic treatment;
* Known to have a history of severe allergic reactions to the drug and its components, planned chemotherapy drugs, and those with a history of severe allergic reactions;
* Suffering from or suspected of active autoimmune diseases, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory intestinal diseases, etc., except: type I diabetes and hypothyroidism that can be controlled through stable dose replacement treatment, and skin diseases that do not require systemic treatment (such as psoriasis, vitiligo);
* History of interstitial lung disease or drug-induced interstitial lung disease or pneumonia in the past;
* Corticosteroid drugs (prednisone\>10mg/day or equivalent dose) or other immunosuppressive drugs received systemically within 14 days prior to the first study medication;
* Individuals with a history of immunodeficiency, including those with other acquired or congenital immunodeficiency diseases, those with a history of organ transplantation, or those who have received allogeneic hematopoietic stem cell transplantation or solid organ transplantation; Received live vaccination within 4 weeks before the first study medication;
* Suffering from serious cardiovascular and cerebrovascular diseases: a) poorly controlled hypertension or pulmonary arterial hypertension; b) Unstable angina or myocardial infarction, coronary artery bypass grafting or stent implantation within 6 months prior to study medication; c) Chronic heart failure with heart function ≥ 2 (NYHA classification by the New York Heart Association); d) Left ventricular ejection fraction (LVEF)\<50%; e) Various severe arrhythmias requiring medication treatment (excluding atrial fibrillation or paroxysmal supraventricular tachycardia). For example, male QTcF\>450 milliseconds or female QTcF\>470 milliseconds, complete left bundle branch block, grade III block; f) Cerebrovascular accident (CVA) or transient ischemic attack (TIA) occurred within 6 months prior to the study medication;
* Positive result of human immunodeficiency virus (HIV) antibody test, active hepatitis B or C. The following conditions are allowed to participate in this study: a) hepatitis B core antibody (HBcAb) or hepatitis B surface antigen (HBsAg) is positive, but HBV DNA is lower than the lower limit of the detection value of the research center (negative) or less than 500IU/ML, and the active infection is excluded according to the judgment of the researcher based on clinical treatment and performance; b) Individuals with positive hepatitis C antibodies and HCV RNA below the lower limit (negative) of the detection value at the research center;
* Suffering from other active malignant tumors other than the research disease within 5 years, except for malignant tumors that can be expected to recover after treatment (including but not limited to fully treated thyroid cancer, cervical carcinoma in situ, basal or squamous cell carcinoma, or breast ductal carcinoma in situ treated with radical surgery);
* Individuals with a history of substance abuse and inability to quit, or those with a history of mental disorders;
* Pregnant or lactating women;
* The researcher believes that the patient is not suitable to participate in any other circumstances of this study.