Sintilimab Combined With Metformin in First-Line Chemotherapy Refractory Advanced NSCLC Patients

Exclusion Criteria

• •1. Participants should not have received metformin within 6 months prior to registration
• •2. In the past, participants have received anti PD-1, anti PD-L1 or anti PD-L2 drugs or drugs targeting another stimulation or synergistic inhibition of T cell receptors (such as Cytotoxic T-Lymphocyte Antigen 4 \[CTLA-4\] and CD137)
• •3. Received the following treatment:
• •Within 2 weeks before the first administration, 1). Received systemic therapy with Chinese adult drugs or immunomodulatory drugs (including thymosine and interferon, except for topical use to control pleural effusion) with anticancer indications 2). 4 weeks prior to the first administration, received any investigational drug therapy or use of research instruments 3). Receive an overdose of immunosuppressive agents (systemic glucocorticoid over 10 mg/ day prednisone or its equivalent) within 4 weeks prior to the first dose 4). Live vaccine was given within 4 weeks before the first dose Note: inactivated virus vaccine for seasonal influenza is allowed within 30 days prior to the first dose, but live attenuated influenza vaccine for intranasal administration is not allowed 5). Major surgery (such as an open cavity, thoracotomy, or laparotomy), or unhealed surgical wounds, ulcers, or fractures, has been performed within 4 weeks prior to the first administration 6). The adverse reactions of any previous anti-tumor treatment did not return to CTCAE ≤level 1(excluding hair loss and laboratory tests without clinical significance).
• •4. Participants who suffer from type 1 or type 2 diabetes, or high blood sugar that require medication
• •5. Active autoimmune diseases requiring systemic therapy (e.g. the use of disease-relieving drugs/corticosteroids or immunosuppressants) occurred within 2 years prior to the first administration. Alternative therapies (such as thyroxine or physiological corticosteroids for adrenal or pituitary insufficiency) are not considered systemic
• •6. Allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation are known
• •7. Allergic reaction to the active ingredients or any adjuncts of Sintilimab or metformin
• •8. History of lactic acid or other metabolic acidosis
• •9. Symptomatic central nervous metastasis and/or cancerous meningitis
• •10. Interstitial pulmonary disease or previous lung disease requires oral or intravenous hormone control
• •11. Clinically uncontrollable third interstitial effusion, such as pleural and ascites, which cannot be controlled by drainage or other methods before enrollment
• •12. Other malignancies were diagnosed within 5 years prior to the first administration, with the exception of radical cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, and/or radical carcinoma in situ
• •13. Suffering from other serious uncontrollable diseases, including but not limited to 1). Kidney disease or renal dysfunction caused by heart failure (shock), acute myocardial infarction, sepsis, etc. \[serum creatinine(Cr)≥1.5mg/dL (male), ≥ 1.4mg/dL (female) or creatinine clearance rate (CrCl)≤ 60mL/min\] 2). Congestive heart failure requiring medication (grade III to IV, New York Heart Association \[NYHA\] classification), unstable angina, poorly controlled and clinically significant arrhythmia 3). A severe infection that requires medical treatment 4). Past cardiopulmonary disease, current need drugs or oxygen support 5). Chronic alcoholism or risk of chronic alcoholism was assessed by investigator 6). HIV Infected person (HIV antibody positive) 7). Untreated active hepatitis b Note: Subjects with hepatitis b who meet the following criteria are also eligible for inclusion: before the first dose, hepatitis B virus (HBV) DNA is less than 1×103 copy number /ml (200IU/ ml), and subjects should receive anti-HBV treatment throughout the study to avoid reactivation of the virus 8). For subjects with anti-hepatitis B core antigen (HBC) (+), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but virus reactivation is monitored closely 9). Subjects with active HCV infection (HCV antibody positive and HCV-RNA level higher than the detection limit) 10). Active tuberculosis, etc 11). Any arterial thrombosis, embolism or ischemia, such as cerebrovascular accident or transient ischemic attack, occurred within 6 months before the inclusion of treatment 12). Clinical active diverticulitis, abdominal abscess, gastrointestinal ulcer, etc 13). Uncontrolled hypercalcemia (\> 1.5 mmol/L of calcium ions or \> 12 mg/dL of calcium or serum calcium \> ULN after correction) or symptomatic hypercalcemia requiring continued bisphosphonate therapy
• •14. Other acute or chronic disease, mental illness, or laboratory abnormalities that may result in increased risk of study participation or drug administration, or interfere with the interpretation of the study results, and disqualify participants from participating in the study according to the judgment of the investigator
• •15. Pregnant or lactating women