Assessing Safety and Efficacy of Sintilimab and Metformin Combination Therapy in SCLC

Inclusion Criteria:

1. Male or female patient, age≥18 and≤65;

2. Eastern Cooperative Oncology Group (ECOG) performance status ≤2;

3. The life expectancy of greater than 12 weeks;

4. Participants must have histologically or cytologically confirmed metastatic orextended disease of SCLC (ED-SCLC).

5. According to RECIST1.1, participants must have been confirmed Disease progression (within 6 months, confirmed by imaging test)after platinum-based doublet chemotherapyOR after (PFS>6 months, ) platinum-based doublet chemotherapy and refused to continuechemotherapy, OR after second-line or more lines of systemic chemotherapy limiteddisease SCLC (LD-SCLC) patients with disease progression after Synchronouschemoradiotherapy, must receive firstline systematic platinum-based doubletchemotherapy and refused to receive chemotherapy again.

6. Evaluable or measurable lesion is required, defined as at least one lesion (not brainmetastasis) that can be accurately measured based on RECIST 1.1;

7. Participant need to provided tumor tissue (from an archival tumor sample obtainedwithin 1 year or from a new biopsy sample) for PD-L1 immunohistochemical (IHC) assay,and PD-L1expression in more than 1% cells is required;

8. Participant is able to the ability to swallow oral medications

9. Participants have to meet the following criteria to ensure function of vital organs: Absolute neutrophil count (ANC) ≥1.5×109/L or White blood cell count >3.5×109/L;Platelets >80×109/L; Hemoglobin (HGB)≥90 g/L;Serum total bilirubin ≤ 1.5 xupper limit of normal (ULN); AST(SGOT)/ALT(SGPT) ≤2.5 ×ULN; ALB≥2.8g/dL;Serumcreatinine ≤ 1.5 x institutional ULN OR creatinine clearance ≥40 mL/min using theCockcroft-Gault equation

10. Participants must agree to use adequate contraception (hormonal or barrier method ofbirth control; abstinence) through the treatment, and for at least 180 days after thelast dose of study treatment; Participants must have the ability to understand and bewilling to sign a written informed consent document.

Exclusion Criteria:

1. Participants who were diagnosed as mixed pathological type of small cell lung cancer

2. Participants who had long-term use of metformin (>2 weeks) 6 months prior to studyentry, or diagnosed with type-2 diabetes,

3. Participants received treatment with anti-PD1, -PDL1, -CTLA4, -CD137 inhibitorsbefore, or any therapy specifically targeting T-cell co-stimulation or checkpointpathways.

4. Participants received cellular immunotherapy before

5. Participants with Uncontrolled intercurrent illness including, but not limited to: Ongoing or active infection; Known history of Human Immunodeficiency Virus (HIV)infection Acute or chronic active hepatitis B (HBV DNA >1*10^3 copies/ml or >200IU/mL) or, acute or chronic active hepatitis C (with a positive Hepatitis C antibodytest result) Active tuberculosis Congestive heart failure (Class III-IV, according toNew York Heart Association classification), or and clinically significant Cardiacarrhythmia if poorly controlled; Uncontrolled arterial hypertension (systolic bloodpressure ≥160mmHg or diastolic blood pressure ≥100mmHg) Any arterial thrombosis,embolism, ischemia, myocardial infarction, unstable angina, or cerebrovascularaccident within 6 months prior to enrollment,

6. Participants with symptomatic Central nervous metastasis or meningeal carcinomatosisare excluded; Participants with asymptomatic brain metastases or with brain metastasesthat have been treated and stable in a subsequent scan are allowed to include if thereis measurable lesion outside the Central nervous system and no history of intracranialhemorrhage, and not midbrain, pons, cerebellum, medulla or spinal cord metastasis, anddo not need glucocorticoid therapy.

7. Participants receiving glucocorticoid (>30 mg prednisone equivalent a day) or anyImmunosuppressive drug within 14 days prior to study recruitment; Participantsreceiving inhaled or Topical corticosteroids, adrenal corticosteroid replacementtherapy (>10 mg prednisone equivalent a day) are allowed if they have no activeautoimmune disease

8. Participants with a known additional malignancy (Except for Non-melanoma skin cancerand the following in situ carcinoma: in situ bladder carcinoma, in situ gastriccarcinoma, in situ colonic carcinoma, in situ endometrial carcinoma, in situ cervicalcarcinoma /dysplasia, in situ melanoma carcinoma and in situ breast Carcinoma) unlessthey Maintained Complete Remission for at least 5 years and do not need correspondingtreatment during the study

9. Participants who have not recovered (i.e., ≤ Grade 1 according to NCI CTCAE V4or atbaseline) from adverse effects due to a previously administered agent.

10. Participants who have uncontrollable effusion, such as pleural and ascites that cannotbe controlled by drainage or other treatment

11. Patients who have active autoimmune diseases; excluding patients whose activeautoimmune disease is caused by Vitiligo or asthma that is completely relieved inchildhood and Patients with hypothyroidism requiring only hormone replacement therapy

12. Patients with known Allogeneic organ transplantation (except corneal transplantation)or allogeneic hematopoietic stem cell transplantation

13. Patients who are pregnant or breastfeeding,

14. Patients who are allergic to monoclonal antibody drugs

15. Patients who have contraindications to metformin including severe allergic reactionsand intolerance

16. Patients who are not eligible for this study, as Assessed by Investigator