1. Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses.

NOTE: If a participant declines to participate in any voluntary exploratory research and/or optional genetic component of the study, there will be no penalty or loss of benefit to the participant, and he/she will not be excluded from other aspects of the study.

2. Age ≥ 18 years at the time of screening.

3. Eastern Cooperative Oncology Group performance status (ECOG PS: 0-2) with no deterioration over the previous 2 weeks.

4. Life expectancy ≥ 12 weeks.

5. Progressive cancer at the time of study entry.

6. Female participants of childbearing potential:

   (a) Must have a negative pregnancy test result at screening and prior to each cycle of study treatment.

   (b) If sexually active with a non-sterilised male partner, must use at least one highly effective method of birth control plus a barrier method (eg, condom with spermicide [in accordance with local guidelines]) from screening to approximately 6 months after the last dose of study treatment. Refer to Appendix F for definitions of females of childbearing potential and highly effective methods of contraception.

7. Female participants 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 treatment.

8. 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 (Note: Male condoms are not reliable as a sole contraception method. In countries where spermicide is not approved, use of male condoms without spermicide is permitted).

9. IT IS STRONGLY RECOMMENDED THAT female partners of male participants 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. Refer to Appendix F for definitions of females of childbearing potential and highly effective methods of contraception. Other requirements for contraception in females of childbearing potential are detailed in the module-specific inclusion criteria.

10. 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.

11. Adequate organ and marrow function (in the absence of transfusions or growth factor support within 14 days prior to enrolment).

12. Participants should be capable of self-administering oral formulations.

13. 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 (if, for example, it is routine at a site to undertake biopsy of metastatic lesions if deemed safe).

1. Treatment with any of the following:

   (a) Any investigational agents or study interventions 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 the following time periods prior to the first dose of study intervention: (i) Cytotoxic and non-cytotoxic treatment: 3 weeks or 5 half-lives (whichever is shorter) (ii) Biological products including immuno-oncology agents: 4 weeks before enrolment.

2. Any live virus or bacterial cancer vaccine within 4 weeks of the first dose of study intervention.

3. Major surgery within 4 weeks of the first dose of study intervention.

4. 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.

5. 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.
Note: Participants may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to > Grade 2 for at least 3 months prior to enrolment and managed with standard of care treatment) that the Investigator deems related to previous anti-cancer therapy, such as: (a) Chemotherapy-induced neuropathy (b) Fatigue (c) Residual toxicities from prior immune-oncology treatment: Grade 1 or Grade 2 (d) Endocrinopathies which may include: (i) Hypothyroidism/hyperthyroidism (ii) Type 1 diabetes (iii) Hyperglycaemia (iv) Adrenal insufficiency (v) Adrenalitis (vi) Skin hypopigmentation (vitiligo)

6. Any known history of persisting (> 2 weeks) severe pancytopenia due to any cause (absolute neutrophil count [ANC] < 0.5 × 109 /L or platelets < 50 × 109 /L).

7. Participants with spinal cord compression are excluded unless they are 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. Participants with evidence of impending spinal cord compression on imaging at screening should receive local therapy before study enrolment.

8. History of uncontrolled seizures (despite adequate antiepileptic therapy) or with need for concurrent administration of more than 2 antiepileptic drugs, or history of epileptic disorder or any seizure history unrelated to tumour.

9. History of severe brain injury or stroke.

10. 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.

11. 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.

12. Any known predisposition to bleeding (eg, active peptic ulceration, recent [within 6 months] haemorrhagic stroke, proliferative diabetic retinopathy).

13. Any of the following cardiac criteria:

   (a) Mean resting corrected QTcF >450 milliseconds obtained from triplicate ECGs and averaged, recorded within 5 minutes

   (b) Any factors that increase the risk of QT prolongation or risk of arrhythmic events such as hypokalaemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years of age or any concomitant medication known to prolong the QT interval and/or have a known risk of Torsades de Pointes (see Appendix G)

   (c) Any clinically important abnormalities in rhythm, conduction or morphology of resting ECG, eg, complete left bundle branch block, second or third degree atrioventricular (AV) block and clinically significant sinus node dysfunction not treated with pacemaker.

14. Other cardiovascular diseases as defined by any of the following:

   (a) Symptomatic heart failure (as defined by New York Heart Association [NYHA] class ≥ 2)

   (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; participants with atrial fibrillation and optimally controlled ventricular rate (resting HR < 100 bpm) are permitted

   (h) Transient ischaemic attack, or stroke within 6 months prior to screening

   (i) Participants with symptomatic hypotension at screening.

15. Participants with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML. Note: Participants with leukaemia who have been cured with bone marrow transplant at least 5 years before are eligible.

16. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD9574.

17. Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

18. 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 (no increase for 7 days) prior to the baseline MRI.

19. Any concurrent anti-cancer therapy or concurrent use of prohibited medications listed in Section 6.6.

20. 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.

21. 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.

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

23. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).

24. Previous study intervention assignment in the present study (ie, dosing with AZD9574 previously initiated in this study).

In addition, the following are considered criteria for exclusion from the exploratory genetic research:

• Previous allogeneic bone marrow transplant.

• Non-leukocyte depleted whole blood transfusion within 120 days of the date of the genetic sample collection.