Chemo-Immunotherapy Followed by Durvalumab and Ceralasertib in Treatment Naïve Patients With Extensive Stage Small Cell Lung Cancer

Inclusion Criteria:

--Palliative radiation: for painful bony lesion must be completed prior togistration and recovered from significant bone marrow toxicity. For patients whoved WBRT, 14 days washout is required prior to study therapy. Patient's must beds without worsening of symptoms related to brain metastases. Patient shouldbe on stable doses of anti-convulsant.Demonstrate adequate organ function as defined in the protocol; all screening labs tobe obtained within 14 days prior to registrationHematologicalAbsolute Neutrophil Count (ANC) >/= 1500/mm^3Platelet >/= 100,000/mm^3Hemoglobin (Hgb) >/= 9 g/dLRenalCreatinine /= 50 mL/min using the Cockcroft-Gaultula if creatinine is more than 1.5 x ULN (60 mL/min if receivingCisplatin)HepaticBilirubin 5.6.2.3 of theull details.vidence of post-menopausal status or negative urinary or serum pregnancy test forusal patients. Women will be considered post-menopausal if they havebeen amenorrheic for 12 months without an alternative medical cause. The followingge-specific requirements apply:Women <50 years of age would be considered post-menopausal if they have beenheic for 12 months or more following cessation of exogenous hormonald if they have luteinizing hormone and follicle-stimulating hormonevels in the post-menopausal range for the institution or underwent surgicalzation (bilateral oophorectomy or hysterectomy).Women ≥50 years of age would be considered post-menopausal if they have beenheic for 12 months or more following cessation of all exogenous hormonalhad radiation-induced menopause with last menses >1 year ago, hadhemotherapy-induced menopause with last menses >1 year ago, or underwenturgical sterilization (bilateral oophorectomy, bilateral salpingectomy orhysterectomy).As determined by the enrolling physician or protocol designee, ability of the subjectunderstand and comply with study procedures for the entire length of the studyAbility to swallow and retain oral medicationust have a life expectancy of at least 12 weeksusion Criteria:Prior systemic therapy for extensive stage or recurrent SCLCPatients with recurrent SCLC, who received chemotherapy or definitive chest radiationhe past for limited-stage SCLC.Clinically significant active infection requiring systemic therapyPregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while theher is being treated on study).Participants who have undergone major surgery within 28 days before first dose ofudy drugParticipants who are currently receiving any other investigational agentsActive malignancy requiring therapy other than small cell lung cancer, excluding:kin cancer, noninvasive colonic polyps, superficial bladder tumors,vical cancer in-situ, ductal carcinoma in situ of the breast, monoclonal B-cellymphocytosis, or monoclonal gammopathy of undetermined significance.Diagnosis of immunodeficiency or is receiving systemic steroid therapy (> 10 mg ofdnisone or equivalent) or any other form of immunosuppressive therapy within 7 daysudy enrolment. Patient's on physiologic corticosteroid replacement therapydrenal or pituitary insufficiency, etc.) is not considered a form of systemic. Topical, inhaled or intra-articular steroids are not considered as systemicds. Steroids as premedication for hypersensitivity reaction (e.g. CT scandication) or prior to chemotherapy is allowed.Active autoimmune or inflammatory disorders (including inflammatory bowel disease[e.g., colitis or Crohn's disease], systemic lupus erythematosus, or Wegener syndrome[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis,hypophysitis, uveitis, etc]). The following are exceptions to this criterion:Patients with vitiligo or alopeciaPatients with hyperthyroidism or hypothyroidism (e.g., following Hashimotoyndrome) clinically stable on hormone replacementAny chronic skin condition that does not require systemic immunosuppressiveherapyPatients with celiac disease controlled by diet aloneDiabetes mellitus with or without insulin replacement therapyHas history of immune therapy related pneumonitis that required steroidsPatients with untreated or symptomatic central nervous system (CNS) metastases orgeal carcinomatosis will be excluded. Previously treated CNS metastases andhave no requirement for steroids for at least 2 weeks prior to study entry is allowed.Anticonvulsant therapy at a stable dose is permitted and must not have seizures for at2 weeks prior to study entry. May have residual symptoms as new baseline. Brainging with either MRI (preferred) or CT with contrast must be performed on allubjects at screening to evaluate brain metastases.Known history of Hepatitis B (known positive HBV surface antigen (HBsAg) result),hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies). Patientsve for hepatitis C (HCV) antibody are eligible only if polymerase chain reactiongative for HCV RNAKnown history of active tuberculosisHistory of allogeneic stem cell or solid organ transplantHistory of Ataxia telangiectasiad intercurrent illness including, but not limited to, serious and activeuncontrolled infection, symptomatic congestive heart failure (NYHA class III-IV),ve inflammatory bowel disease, unstable angina pectoris, uncontrolled seizures, orychiatric illness/social situations that would limit compliance with studyquirementsParticipants with a known hypersensitivity to durvalumab, ceralasertib or anyhe productPatients who have been vaccinated with live, attenuated vaccines within 4 weeks ofdose of study drugRefractory nausea and vomiting, chronic gastrointestinal diseases or previousgnificant bowel resection, with clinically significant sequelae that would precludedequate absorption of ceralasertib.Patients weighing <= 30 Kg.Participants may not be receiving any medications or substances that are potenthibitors or inducers of CYP3A4 (Appendix B of the protocol).There is a required wash-out period of 5 half-lives from such agents prior tog ceralasertib, or three weeks for St. John's Wort.For non-potent inhibitors or inducers of CYP3A4, the decision to allow a patienthe study is per investigator best judgement. Note these includezole antifungals, macrolide antibiotics, and other medications listed inhe concomitant medications section. As part of the enrollment/informed consentdures, the patient will be counseled on the risk of interactions with othergents, and what to do if new medications need to be prescribed or if the patientdering a new over-the-counter medicine or herbal product.ure of other drugs metabolized by CYP3A4 and/or CYP2B6 may be reduced anddditional monitoring may be required.The use of herbal supplements or 'folk remedies' (and medications and foods thatgnificantly modulate CYP3A activity) should be discouraged. If deemedy, such products may be administered with caution and the reason for usedocumented in the CRF.