A Study to Assess the Safety and Tolerability of Adavosertib for Patients With Advanced Solid Tumours

Exclusion Criteria

• •1. Persistent toxicities (Common Terminology Criteria for Adverse Events \[CTCAE\] Grade \> 2) caused by previous anticancer therapy, excluding alopecia and CTCAE Grade 2 peripheral neuropathy.
• •2. Refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of adavosertib.
• •3. Any significant cardiac diseases currently or within the last 6 months such as:
• •1. unstable angina pectoris
• •2. acute myocardial infarction, congestive heart failure
• •3. conduction abnormality not controlled with pacemaker or medication
• •4. significant ventricular or supraventricular arrhythmias
• •4. Any of the following: History or current evidence of congenital long QT syndrome; concomitant medications known to prolong QT interval or history of medication-related QT prolongation.
• •5. Known to have tested positive for human immunodeficiency virus or active tuberculosis infection.
• •6. Known active hepatitis infection, positive hepatitis C antibody, hepatitis B virus surface antigen or hepatitis B virus core antibody, at screening.
• •7. Any evidence of diseases (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension, renal transplant, active infections, and active bleeding diseases) which prohibit participating in the study.
• •8. Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention.
• •9. Use of an anti-cancer treatment drug ≤ 21 days (≤ 6 weeks for nitroureas or mitomycin C) or use of an investigational product within 5 half-lives prior to the first dose of adavosertib.
• •10. Patient uses drugs that are sensitive to CYP3A4 substrates or CYP3A4 substrates with a narrow therapeutic index, or are moderate to strong inhibitors/inducers of CYP3A4 which cannot be discontinued 2 weeks or 5 halflives (whichever is longer) prior to Day 1 of dosing.
• •11. Receipt of live virus and live bacterial vaccines whilst the patient is receiving the study intervention and during the 30-day follow-up period. Inactivated vaccines are permitted.
• •12. Currently pregnant (confirmed with positive pregnancy test) or breast feeding.