Phase Ib Study to Determine MTD of AZD1775 Monotherapy in Patients With Locally Advanced or Metastatic Solid Tumours.

Inclusion Criteria:

1. Prior palliative radiation completed ≥ 7 days prior to the start of AZD1775 and recovered from any acute adverse effects.
2. ECOG PS score 0 or 1.
3. Baseline laboratory values:

   * ANC ≥1500/μL
   * Hemoglobin (HgB) ≥9 g/dL
   * Platelets ≥100,000/μL
   * ALT and AST ≤3 x ULN or ≤5 x ULN if known hepatic metastases.
   * Serum bilirubin WNL or ≤1.5 x ULN in patients with liver metastases; or total bilirubin ≤3.0 x ULN with direct bilirubin WNL in patients with well documented Gilbert's Syndrome.
   * Serum creatinine ≤1.5 x ULN, or measured creatinine clearance ≥45 mL/min.
4. Females who are not of child-bearing potential and fertile females of child-bearing potential who agree to use adequate contraceptive measures, who are not breastfeeding, and who have a negative serum or urine pregnancy test within 3 days prior to, and on the day of starting study treatment.
5. Males willing to use at least one medically acceptable form of contraception for duration of study and for 3 months after treatment stops.
6. Predicted life expectancy ≥12 wks.
7. Age ≥18
8. Histologically or cytologically documented locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
9. Measurable or non-measurable disease according to RECIST v1.1.

Exclusion Criteria:

1. Use of a treatment drug 21 days or 5 half-lives (whichever is shorter) prior to AZD1775. For drugs for which 5 half-lives is ≤21 days, a minimum of 10 days between termination of the prior treatment and administration of AZD1775 treatment is required.
2. Use of an investigational drug during the past 30 days or 5 half-lives (whichever is longer) prior to first dose of study treatment.
3. Major surgical procedures ≤28 days of beginning study treatment, or minor surgical procedures ≤7 days.
4. Grade \>1 toxicity from prior therapy (except alopecia or anorexia).
5. Inability to swallow oral medications.
6. Palliative radiation therapy completed ≤7 days prior to start of study drug.
7. Known malignant CNS disease other than neurologically stable, treated brain metastases.
8. Rx or non-Rx drugs or 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 which cannot be discontinued 2 weeks prior to dosing and withheld until 2 weeks after the last dose of study drug.
9. Patients should stop using herbal medications 7 days prior to first dose of study treatment.
10. Any of the following cardiac diseases currently or within the last 6 months as defined by New York Heart Association (NYHA) ≥ 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)
11. History of Torsades de pointes unless all risk factors that contributed to Torsades have been corrected.

11\. Mean resting QTc interval \>470 msec (as calculated per institutional standards) at study entry obtained from 3 ECGs within 5 minutes or congenital long QT syndrome.

12\. Pregnant or lactating. 13. Serious 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.

14\. Presence of other active invasive cancers. 15. Psychological, familial, sociological, or geographical conditions that do not permit compliance with protocol.