AZD1775 Continued Access Study to Assess Safety and Tolerability for Patients Enrolled in AZD1775 Clinical Pharmacology Studies

This is an open-label, non-randomised study designed to provide continued access to AZD1775
for eligible patients with advanced solid tumours who have previously completed an AZD1775
clinical pharmacology study and to investigate the safety of a once daily monotherapy regimen
of AZD1775 in patients with advanced solid tumours.

All patients who completed 1 of the parent clinical pharmacology studies are eligible for
this study after a washout period of at least 4 days (minimum duration defined in the parent
study protocol) and meet the eligibility criteria specified in this protocol. Patients who
discontinue early from the parent study will be considered by the Sponsor and treating
physician on a case-by-case basis.

During the study, patients will continue to receive AZD1775 as long as they are benefiting
from treatment in the Investigator's opinion and do not meet any other discontinuation
criteria.

Inclusion Criteria:

For inclusion in this study, patients must fulfil the following criteria:

- Has read and understands the informed consent form (ICF) and has given written
informed consent prior to any study procedures.

- Female or male aged ≥18 years.

- Has completed 1 of the parent AZD1775 clinical pharmacology studies (ie, D6014C00002,
D6014C00003, D6014C00004, D6014C00005, or D6014C00006) and in the Investigator's
opinion will continue to benefit from treatment with AZD1775. Patients who discontinue
early from the parent study will be considered by the Sponsor and treating physician
on a case-by-case basis.

- Any prior radiation must have been completed at least 7 days prior to the start of
study treatment, and patients must have recovered from any acute effects prior to the
start of study treatment.

- Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 to 1.

- Baseline laboratory values within 7 days of study treatment initiation in the CA
study:

- Absolute neutrophil count (ANC) ≥1500/μL.

- Haemoglobin ≥9 g/dL.

- Platelets ≥100,000/μL.

- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤3 x upper
limit of normal (ULN) or ≤5 x ULN if known hepatic metastases.

- Serum bilirubin within normal limits or ≤1.5 x ULN in patients with liver
metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin within normal
limits in patients with well documented Gilbert's Syndrome.

- Serum creatinine ≤1.5 x ULN, or measured creatinine clearance (CrCl) calculated
by Cockcroft-Gault method ≥45 mL/min (confirmation of creatinine clearance is
only required when creatinine is >1.5 x ULN) CrCl (glomerular filtration rate) =
(140-age) x (weight/kg) x Fa (72 x serum creatinine mg/dL) where F = 0.85 for
females and F = 1 for males.

- Female patients who are of non-childbearing potential and fertile women of
childbearing potential (WoCBP) who agree to use adequate contraceptive measures that
are in place during screening (or consent), for the duration of the study, and for 1
month after treatment stops; who are not breastfeeding; and who have a negative serum
or urine pregnancy test prior to the start of study treatment.

- Male patients must be willing to use barrier contraception (ie, condoms) for the
duration of the study and for 3 months after study treatment discontinuation.

- Willingness and ability to comply with the study and the follow-up procedures.

Exclusion Criteria:

Patients must not enrol in this study if any of the following exclusion criteria are
fulfilled:

- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
personnel and/or personnel at the study centre).

- Previous enrolment and received study treatment in the present study. Patients can,
however, be re-screened if the reason for the screen failure no longer exists.

- Concurrent enrolment in another clinical study, unless it is an observational
(non-interventional) clinical study or the follow-up period of an interventional
study.

- Must not have received another systemic anti-cancer therapy in the interval following
participation in the AZD1775 clinical pharmacology study and the start of treatment on
the CA protocol.

- Not developed any clinical findings suggestive of brain metastasis. Patients continue
to be neurological stable and remain off systemic corticosteroids following treatment
of known brain metastases.

- Did not tolerate AZD1775 in the parent study in the opinion of the Investigator.

- Where a course of palliative radiotherapy was indicated, the last fraction must have
been delivered before the start of study treatment on the CA study.

- Major surgical procedures ≤28 days of beginning study treatment, or minor surgical
procedures ≤7 days. No waiting period required following port-a-cath placement or
other central venous access placement.

- Grade >1 toxicities from prior therapy, according to the Common Terminology Criteria
for Adverse Events (CTCAE), excluding alopecia or anorexia.

- Continue to be able to swallow oral medication, did not undergo placement of a
percutaneous endoscopic gastrostomy tube and did not require total parenteral
nutrition.

- Has had prescription or non-prescription drugs or other products known to be sensitive
to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or to be
moderate to strong inhibitors/inducers of CYP3A4 between the parent study and entry
into this CA study. Co administration of aprepitant or fosaprepitant during this study
is prohibited.

- Has consumed herbal preparations between the parent study and entry into this CA
study.

- Has consumed grapefruit, grapefruit juice, Seville oranges, Seville orange marmalade,
or other products containing grapefruit or Seville oranges between the parent study
and entry into the CA study.

- Any known hypersensitivity or contraindication to AZD1775 or to the components
thereof.

- Any of the following cardiac diseases currently or within the last 6 months as defined
by the New York Heart Association ≥Class 2:

- Unstable angina pectoris.

- Congestive heart failure.

- Acute myocardial infarction.

- Conduction abnormality not controlled with pacemaker or medication.

- Significant ventricular or supraventricular arrhythmias (patients with chronic
rate-controlled atrial fibrillation in the absence of other cardiac abnormalities
are eligible).

- AZD1775 should not be given to patients who have a history of Torsades de pointes
unless all risk factors that contributed to Torsades have been corrected. AZD1775 has
not been studied in patients with ventricular arrhythmias or recent myocardial
infarction.

- Patient with mean resting QTc interval (specifically QTc calculated using the
Fridericia formula [QTcF]) >450 ms for males and >470 ms for females from 3
electrocardiograms (ECGs) performed within 2 to 5 minutes apart during screening, or
congenital long QT syndrome.

- Pregnant or lactating female patients.

- Serious, symptomatic active infection at the time of study entry, or another serious
underlying medical condition that would impair the ability of the patient to receive
study treatment.

- Active infection with hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).