SGI-110 Plus Durvalumab/Tremelimumab in SCLC

For inclusion in the study, patients should fulfill the following criteria: 1. Written informed consent and any locally-required authorization (e.g., HIPAA in the USA, EU Data Privacy Directive in the EU) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations 2. Age ≥ 18 years at time of study entry 3. Eastern Cooperative Oncology Group (ECOG performance status of 0 or 1) 4. Life expectancy of ≥ 12 weeks 5. Adequate normal organ and marrow function as defined below Hemoglobin ≥ 9.0 g/dL Absolute neutrophil count (ANC) ≥ 1.5 x 109/L (\> 1500 per mm3) Platelet count ≥ 100 x 109/L (\>100,000 per mm3) Serum total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (for patients with a diagnosis of Gilbert's syndrome, direct bilirubin ≤ 1.5 x ULN) AST (SGOT)/ALT (SGPT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5x ULN Serum creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance: Males: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) . 72 x serum creatinine (mg/dL) Females: Creatinine CL (mL/min) = Weight (kg) x (140 - Age) x 0.85 72 x serum creatinine (mg/dL) 6. Females of childbearing potential who are sexually active with a non-sterilized male partner must use a highly effective method of contraception from the time of screening, and must agree to continue using such precautions for 180 days after the final dose of investigational product. Cessation of contraception after this point should be discussed with a responsible physician. Periodic abstinence, the rhythm method, and the withdrawal method are not acceptable methods of contraception. Female subjects must also refrain from egg cell donation for 180 days after the final dose of investigational product. A) Females of childbearing potential are defined as those who are not surgically sterile (i.e. bilateral tubal ligation, bilateral oophorectomy, or complete hysterectomy) or those who are not postmenopausal (defined as 12 months with no menses with postmenopausal gonadotropin levels \[luteinizing hormone and follicle-stimulating hormone\], or estradiol levels within the postmenopausal range according to local guidelines without an alternative medical cause). B) A highly effective method of contraception is defined as one that results in a low failure rate (i.e. less than 1% per year) when used consistently and correctly. 7. Subject is willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 8. Subjects must have a histologically confirmed diagnosis of small cell lung carcinoma. A fresh, pre-treatment tumor biopsy will be required to evaluate tumor infiltrating lymphocytes, PD-L1 IHC staining, methylation status, etc. as outlined in the study timeline. All subjects are also required to have a C1D8 (or C2D8) biopsy. 9. Subjects must have extensive-stage disease (by NCCN criteria) that is progressive or relapsed after platinum-based chemotherapy. 10. Tumor burden must be radiographically measurable by RECIST criteria. 11. At time of Day 1 of the study, subjects with central nervous system metastases must have been treated and must be asymptomatic and meet the following: 1. No concurrent treatment, inclusive of but not limited to surgery, radiation, and/or corticosteroids 2. Neurologic stability (lack of signs and symptoms greater than baseline prior to XRT) until the time of dosing 3. For radiation treatment, there should be at least 14 days between the last day of stereotactic radiosurgery or gamma-knife treatment and Day 1 of protocol treatment. For WBRT, there should be at least 28 days between last day of WBRT and Day 1 of protocol treatment. 4. Note: patients with leptomeningeal disease or cord compression are excluded from the study.

Subjects should not enter the study if any of the following