Study of AZD9574 as monotherapy and in combination with anti-cancer agents in patients with advanced solid malignancies

Prior treatment

• Treatment with any of the following: (a) Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study intervention (b) Any other anti-cancer treatment within 5 half-lives or 3 weeks for cytotoxic and non-cytotoxic treatment or 4 weeks before enrollment for biological products
• Any concurrent anti-cancer therapy or concurrent use of prohibited medications
• Major surgery within 4 weeks of the first dose of study intervention
• Concurrent enrolment in another clinical study unless it is an observational (non-interventional) clinical study eg. PET imaging study, or during the follow-up period of an interventional study.
• Previous study intervention assignment in the present study Other module specific criteria may apply.
• Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study intervention
• With the exception of alopecia, any unresolved toxicities from prior therapy greater than Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 at the time of starting study intervention
• Spinal cord compression unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of > 10 mg prednisone/day or equivalent for at least 4 weeks prior to start of study intervention
• History of uncontrolled seizures or with need for concurrent administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumour
• Other cardiovascular diseases as defined by any of the following: (a) Symptomatic heart failure (b) Uncontrolled hypertension (c) Hypertensive heart disease with significant left ventricular hypertrophy (d) Acute coronary syndrome/acute myocardial infarction, unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention or coronary artery bypass grafting or cardiac valve replacement/repairment within 6 months (e) Cardiomyopathy of any aetiology (f) Presence of clinically significant valvular heart disease (g) History of atrial or ventricular arrhythmia requiring treatment (h) Transient ischaemic attack, or stroke within 6 months prior to screening (i) Patients with symptomatic hypotension at screening
• Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of the investigational product(s) (IP).
• Known contra-indication to gadolinium-enhanced MRI imaging or, if applicable, not able to be maintained on a stable or decreasing dose of corticosteroid regimen prior to the baseline MRI.

Other illness

• Any condition that, in the opinion of the Investigator, would interfere with evaluation of the study intervention or interpretation of participant safety or study results
• Any known history of persisting (> 2 weeks) severe pancytopenia due to any cause
• Uncontrolled intercurrent illness within the last 12 months, including but not limited to, active interstitial lung disease, serious chronic GI conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent.
• History of severe brain injury or stroke
• As judged by the Investigator, any evidence of severe or uncontrolled systemic diseases, including active bleeding diatheses, active infection including hepatitis B, hepatitis C and human immunodeficiency virus (HIV). Screening for chronic conditions is not required
• Any live virus or bacterial cancer vaccine within 4 weeks of the first dose of study intervention
• Any known predisposition to bleeding
• Patients with myelodysplastic syndrome/acute myeloid leukaemia
• Known allergy or hypersensitivity to IP(s) or any of the excipients of the IP(s)

Lab values

• Any of the following cardiac criteria: (a) Mean resting corrected QT interval (QTcF) >450 milliseconds (b) Any factors that increase the risk of QT prolongation or risk of arrhythmic events (c) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG and clinically significant sinus node dysfunction not treated with pacemaker

Other

• Judgement by the Investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements
• Involvement in the planning and/or conduct of the study

• Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses.
• Male participants must refrain from fathering a child or donating sperm from the start of study intervention and for approximately 3 months after the last dose of study intervention
• Adequate organ and marrow function as defined by the protocol
• Participants should be capable of self-administering oral formulations
• Provision of archival formalin-fixed and paraffin-embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific module. An archival tissue specimen is preferred but a new tissue sample may be used
• Age ≥ 18 years at the time of screening.
• Eastern Cooperative Oncology Group performance status (ECOG PS: 0-2) with no deterioration over the previous 2 weeks.
• Life expectancy ≥ 12 weeks.
• Progressive cancer at the time of study entry.
• Female subjects of childbearing potential: Must have negative pregnancy test result at screening and prior to each cycle administration of study treatment and must use at least one highly effective method of birth control
• Female subjects must not breastfeed and must not donate or retrieve ova for their own use, from screening to approximately 6 months after the last dose of study intervention.
• Non-sterilised male participants who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 3 months after the last dose of study intervention
• Female partners of male participants must also use at least one highly effective method of contraception from screening to approximately 3 months after the last dose of study intervention of the male participant