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