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