An Open-label, Phase II Study of AZD4635 in Patients With Prostate Cancer

Inclusion Criteria for all Patients in all Modules:

• Provision of signed and dated, written informed consent form prior to any mandatory study specific procedures, sampling, and analyses
• Participant must be ≥18 years of age at the time of signing the inform consent form (ICF)
• Participants must have prostate cancer with histological or cytological confirmation
• Participants must have previously received and progressed on standard-of-care therapy(ies)
• Participants must be able to provide an archival tumor tissue sample. If archival tumor tissue is not available, then tissue from a fresh tumor biopsy is required.
• All participants will be required to have a site of disease that is safely accessible for biopsy (paired) upon enrollment unless there are sufficient paired samples for the analysis. Accessible lesions are defined as those which are biopsiable (at screening) and amenable to repeat biopsy (after 2 weeks of AZD4635 therapy), unless clinically contraindicated. The provision of paired biopsies will be closely monitored to ensure the desired number of biopsiable participants are enrolled and investigators are aware of this requirement at all times.
• Participants with measurable disease must have at least 1 documented lesion on either a bone scan or a computed tomography (CT)/ magnetic resonance imaging (MRI) scan that can be followed for response and is suitable for repeated measurement, or participants with non-measurable disease must have measurable PSA ≥1.0 ng/mL if the confirmed rise is the only indication of progression (excluding small cell carcinoma) 8 Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 with no clinical deterioration over the previous 2 weeks prior to the 28-day screening period and likely able to complete at least 12 weeks of treatment.
• Ability to swallow and retain oral medication. 10. Must have life expectancy of at least 12 weeks 11. Body weight ≥ 35 kg at screening 12. Willingness to adhere to the study treatment-specific contraception requirements: Participants must be surgically sterile or using an acceptable method of contraception (defined as barrier methods in conjunction with spermicides) for the duration of the study (from the time they sign ICF) and for 3 months after the last dose of AZD4635 to prevent pregnancy in a female partner. Male participants must not donate or bank sperm for 24 weeks after treatment.

Inclusion Criteria for Modules 1 and 2:

• Participants must have metastatic castrate resistant prostate cancer with histological or cytological confirmation. Participant may have bone-only metastatic disease.
• Participants must have had either orchiectomy or be on luteinizing hormone-releasing hormone (LHRH) agonist or antagonist therapy with testosterone 470 msec obtained from 3 ECGs
• Any clinically important abnormalities in rhythm, conduction, or morphology of resting ECGs, e.g., complete left bundle branch block, third degree heart block
• Any concomitant medication with known QT interval prolongation. Participants receiving a medication(s) known to prolong the QT interval may be discussed with the Medical Monitor or Sponsor for study approval.
• Ejection fraction 2.5 times the upper limit of normal (ULN) if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
• Aspartate aminotransferase (AST) >2.5 times ULN if no demonstrable liver metastases or >5 times ULN in the presence of liver metastases
• Total bilirubin (TBL) >1.5 times ULN
• Creatinine >1.5 times ULN concurrent with creatinine clearance 1.5 times ULN.
• Involvement in the planning and/or conduct of the study (applies to AstraZeneca staff and its representatives and/or staff at the study site).
• Judgment by the Investigator or Medical Monitor that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions and requirements.
• Participation in another clinical interve