Ph II Trial of Carboplatin and Pemetrexed With or Without AZD1775 for Untreated Lung Cancer

Inclusion Criteria * Provision of informed consent prior to any study specific procedures * Histologic or cytologic diagnosis of advanced NSCLC, Recurrent or Stage IV disease (according to American Joint Committee on Cancer (AJCC) staging system, v7.0). * No prior chemotherapy for locally advanced or metastatic disease * Subjects with a known EGFR mutation must have received previous treatment with an EGFR tyrosine kinase inhibitor; and subjects with a known ALK translocation must have received previous treatment with an ALK inhibitor. * No prior radiation therapy to the whole pelvis or to ≥25% of the total bone marrow area. * At least one measurable lesion according to Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 * Mandatory availability of tumour tissue (archival or fresh if archival is not available) for TP53 determination. * Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or 1. * Absolute neutrophil count (ANC) ≥1500/μL * Hemoglobin (Hgb) ≥10 g/dL * Platelets ≥100,000/μL * Alanine aminotransferase (ALT) and aspartate aminotransferase (AST), ≤3.0 x the upper limit of normal (ULN); 5 x ULN if known hepatic metastases * Total bilirubin ≤1.5 x ULN, unless secondary to Gilbert's disease * Serum creatinine ≤1.5 x ULN and a calculate creatinine clearance (CrCl) ≥45 mL/min by the Cockcroft-Gault method * Ability to swallow oral medication * Fertile male subjects willing to use at least one medically acceptable form of birth control for the duration of the study and for 2 weeks after treatment stops * Female subjects who are not of childbearing potential and fertile female subjects of childbearing potential who agree to use adequate contraceptive measures who are not breastfeeding, and who have a negative serum or urine pregnancy test within 72 hours prior to start of study treatment * Predicted life expectancy ≥12 weeks * Must be ≥18 years of age * Willingness and ability to comply with study and follow-up procedures * Ability to understand the nature of this trial and give written informed consent Exclusion criteria * Use of a study drug ≤21 days or 5 half-lives (whichever is shorter) prior to the first dose of AZD1775 * Major surgical procedures ≤28 days of beginning AZD1775, or minor surgical procedures ≤7 days * Known central nervous system (CNS) disease * Subject has had prescription or non-prescription drugs or other products (i.e. grapefruit juice) known to be sensitive CYP3A4 substrates * Any known hypersensitivity or contraindication to the components of study treatment * Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (\[NYHA\] Appendix G) ≥ Class 2 * Corrected QT interval (QTc) \>470 msec (as calculated by Fridericia correction formula) at study entry or congenital long QT syndrome. * Pregnant or lactating * Any serious, active underlying medical condition that would impair the ability of the subjects to receive study treatment * Unable or unwilling to take folic acid or vitamin B12 * Presence of other active cancers, or history of treatment for invasive cancer ≤3 years * Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol