Study of AZD0516 as Monotherapy and in Combination in Participants With Metastatic Prostate Cancer

Main Inclusion Criteria: * Histologically or cytologically confirmed diagnosis of metastatic adenocarcinoma of the prostate. Focal high grade neuroendocrine features are permitted. * Measurable PSA ≥ 1 μg/L (≥ 1 ng/mL). * Surgically or medically castrated with serum testosterone levels ≤ 50 ng/dL (≤ 1.75 nmol/L) within ≤ 28 days before treatment allocation. Ongoing androgen deprivation therapy (ADT) with a gonadotropin releasing hormone (GnRH) modulator for participants who have not undergone bilateral orchiectomy must be initiated at least 2 weeks prior to consent and must continue throughout the study. * Eastern cooperative oncology group (ECOG) performance status of 0 or 1. * Adequate organ and marrow function in the absence of blood transfusion or growth factor support (within 21 days prior to the scheduled first dose of study intervention). * Provision of baseline archival or newly obtained formalin-fixed paraffin-embedded (FFPE) tumour sample is mandatory. * Documented current evidence of metastatic prostate cancer * Life expectancy of at least 12 weeks in the opinion of the investigator * Documented mCRPC progression at screening as assessed by the investigator with at least one of the following criteria: 1. PSA progression defined by a minimum of 3 rising PSA levels with an interval of ≥ 1 week between each determination. The PSA value at the screening visit should be ≥ 1 μg/L (1 ng/mL). 2. Radiographic disease progression in soft tissue based on response evaluation criteria in solid tumors (RECIST) v1.1 criteria with or without PSA progression as per prostate cancer working group 3 (PCWG3). 3. Radiographic disease progression in bone defined as the appearance of 2 or more new bone lesions on a bone scan as per PCWG3 with or without PSA progression. Main Exclusion Criteria: * Cancer related spinal cord compression, or brain metastases 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 study enrolment. * History of leptomeningeal carcinomatosis. * Unresolved toxicities of Grade ≥ 2 (National Cancer Institute Common Terminology Criteria for Adverse Events v5.0) from prior therapy (excluding vitiligo, alopecia, and endocrine disorders that are controlled with replacement hormone therapy). * Uncontrolled intercurrent illness within the last 12 months. * Cardiovascular disorder (History of arrhythmia, uncontrolled hypertension, symptomatic hypotension, history of brain perfusion problems, symptomatic heart failure, prior or current cardiomyopathy, severe valvular heart disease) * History of malignancy * History of non-infectious interstitial lung disease (ILD)/pneumonitis * Active infection exclusions, including tuberculosis and infections with Hepatitis B Virus (HBV), Hepatitis C Virus (HCV) or Human Immunodeficiency Virus (HIV). * Any known predisposition to bleeding * Clinically severe pulmonary compromise * Participants with Myelodysplastic syndrome (MDS)/Acute Myeloid Leukemia (AML) or with features suggestive of MDS/AML. * Previous treatment with a STEAP2 targeting modality, chemotherapeutic agent that inhibits topoisomerase activity or metabolic enzymes.