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

This is a randomised, double-blind, placebo-controlled, phase II trial comparing AZD1775
plus carboplatin and pemetrexed with a maintenance phase.

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