Tremelimumab and Durvalumab With or Without Radiation Therapy in Patients With Relapsed Small Cell Lung Cancer

Inclusion Criteria

• Written informed consent and any locally-required authorization (e.g.,) obtained from the subject prior to performing any protocol-related procedures, including screening evaluations
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• 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 bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); this will not apply to subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤ 5 x ULN
• Serum creatinine clearance (CL) > 40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
• Female subjects must either be of non-reproductive potential (i.e., post-menopausal by history: ≥ 60 years old and no menses for ≥ 1 year without an alternative medical cause; OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of bilateral oophorectomy) or must have a negative serum pregnancy upon study entry
• 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
• Patients must have baseline evaluations performed prior to the first dose of study drug and must meet all inclusion and exclusion criteria
• Patients must have histologically or cytologically confirmed small cell lung cancer
• Patients must have measurable disease, defined as at least one lesion (excluding the lesion for XRT) that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
• Patient must have failed or found to be intolerant of standard frontline platinum-based regimens and must not have received > 2 prior lines of therapy (nota bene [NB]: retreatment with a platinum-based doublet for sensitive relapse counts as another line therapy; however substitution of cisplatin with carboplatin or vice versa due to toxicity does not count as a separate regimen)
• Negative serum pregnancy test within 48 hours before starting study treatment in women with childbearing potential
• Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site)
• Previous enrollment or randomization in the present study
• Treatment with an investigational product during the last 2 weeks
• Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA4), including tremelimumab
• Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤ 14 days prior to the first dose of study drug (≤ 7 days or four half-lives, whichever is longer, prior to the first dose of study drug for subjects who have received prior tyrosine kinase inhibitors [TKIs] [e.g., erlotinib, gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C)
• Mean QT interval corrected for heart rate (QTc) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) using Fredericia's Correction
• Current or prior use of immunosuppressive medication withi