Olaparib and Durvalumab With Carboplatin, Etoposide, and/or Radiation Therapy for the Treatment of Extensive-Stage Small Cell Lung Cancer, PRIO Trial

Exclusion Criteria

• •Histology other than SCLC
• •Prior systemic therapy for ES-SCLC (e.g. chemotherapy, PARP inhibitor, other DNA damage response \[DDR\] inhibitors, PD-1/PD-L1 inhibitors)
• •Patients with untreated brain metastases
• •Patients with spinal cord compression unless considered to have received definitive treatment for this and evidence of clinically stable disease for 28 days
• •Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of study treatment and patients must have recovered from any effects of any major surgery. Note: Local surgery of isolated lesions for palliative intent is acceptable
• •Other malignancy unless curatively treated with no evidence of disease for \>= 3 years except:
• •* Adequately treated non-melanoma skin cancer.
• •* Curatively treated in situ cancer of the cervix; ductal carcinoma in situ (DCIS); stage 1, grade 1 endometrial carcinoma; and in situ bladder cancer
• •Any concurrent anticancer therapy
• •Resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (e.g. unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QT corrected by Fridericia \[QTcF\] prolongation \> 500 ms, electrolyte disturbances, etc.), or patients with congenital long QT syndrome
• •Current or prior use of immunosuppressive medication within 14 days prior to cycle 1 (C1) of study treatment, with the exceptions of intranasal and inhaled corticosteroids, or systemic corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid
• •Active or prior documented inflammatory bowel disease (e.g., Crohn's disease, ulcerative colitis) or pneumonitis
• •Immunocompromised patients, e.g., patients who are known to be serologically positive for human immunodeficiency virus (HIV)
• •Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
• •Patients considered high medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection. Examples include, but are not limited to, uncontrolled ventricular arrhythmia, recent (within 3 months) myocardial infarction, uncontrolled major seizure disorder, unstable spinal cord compression, superior vena cava syndrome, extensive interstitial bilateral lung disease on high resolution computed tomography (HRCT) scan or any psychiatric disorder that prohibits obtaining informed consent
• •Patients with myelodysplastic syndrome (MDS) / acute myeloid leukemia (AML) or with features suggestive of MDS/AML
• •Whole blood transfusions in the last 120 days prior to entry to the study (packed red blood cells and platelet transfusions are acceptable outside of 28 days prior to treatment)
• •Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
• •Concomitant use of known strong CYP3A inhibitors (e.g. itraconazole, telithromycin, clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir, saquinavir, nelfinavir, boceprevir, telaprevir) or moderate CYP3A inhibitors (e.g. ciprofloxacin, erythromycin, diltiazem, fluconazole, verapamil). The required washout period prior to starting study treatment is 2 weeks
• •Concomitant use of known strong (e.g. phenobarbital, enzalutamide, phenytoin, rifampicin, rifabutin, rifapentine, carbamazepine, nevirapine and St John's Wort) or moderate CYP3A inducers (e.g. bosentan, efavirenz, modafinil). The required washout period prior to starting study treatment is 5 weeks for enzalutamide or phenobarbital and 3 weeks for other agents
• •Participation in another clinical study with an investigational product (IP) administered in the last 6 months
• •Involvement in the planning and/or conduct of the study
• •Previous enrollment in the present study
• •Receipt of live attenuated vaccination within 30 days prior to study entry
• •Female subjects who are pregnant, breast-feeding or male or female patients of reproductive potential who are not employing two highly effective methods of birth control
• •Any condition that, in the opinion of the investigator, would interfere with evaluation of study treatment or interpretation of patient safety or study results
• •Known allergy or hypersensitivity to durvalumab, olaparib or any excipients