A Phase I Study of [225Ac]-AZD2284 in Patients With Metastatic Castration-Resistant Prostate Cancer

Main Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Histologically confirmed diagnosis of adenocarcinoma of the prostate without strong clinical suspicion of majority neuroendocrine differentiation. * Must have had prior bilateral orchiectomy and/or ongoing androgen-deprivation therapy and a castrate level of serum/plasma testosterone (\< 50 ng/dL or \< 1.7 nmol/L). * At least one metastatic lesion present on baseline Computed Tomography (CT), Magnetic Resonance Imaging (MRI), or bone scan obtained ≤ 28 days prior to the first dose of Investigational Medicinal Product (IMP). Participants may have non-measurable lesions including bone only metastases. * Adequate organ function * Part A only: Metastatic prostate cancer considered to be stable or progressing metastatic castration resistant prostate cancer (mCRPC). * Part B only: Progressing mCRPC defined as meeting at least one of following documented criteria - 1. Serum/plasma PSA progression 2. Soft-tissue progression 3. Progression of bone disease * Part B Dose Escalation: Previously treated with at least 2 prior lines of systemic anti-cancer therapy for mCRPC. Prior lines must include: 1. At least 1 androgen receptor pathway inhibitor (ARPI) 2. A poly (adp-ribose) polymerase (PARP) inhibitor for participants with known BRCA mutation 3. A checkpoint inhibitor for participants with known microsatellite instability-high (MSI-H), deficient mismatch pair (dMMR), or tumor mutational burden (TMB) ≥ 10 mut/Mb * Part B Dose Expansion: Previously treated with at least 1 prior line of systemic anti-cancer therapy for mCRPC. Prior lines must include: 1. At least 1 ARPI 2. A PARP inhibitor for participants with known BRCA mutation per local practice, unless ineligible per Investigator decision. 3. A checkpoint inhibitor for participants with known MSI-H, dMMR, or TMB ≥ 10 mut/Mb. 4. No previous cytotoxic chemotherapy for CRPC. Taxanes for metastatic hormone sensitive prostate cancer (mHSPC) is acceptable if the last cycle Day 1 was \> 12 months before first study treatment. 5. Previous treatment with prostate specific membrane antigen radioligand therapy (PSMA-RLT) or Radium-223 is allowed but not required. Participants who have had prior radiation therapy, including therapeutic radiopharmaceuticals, external bean radiation therapy (EBRT), and/or brachytherapy are eligible, subject to satisfying all other inclusion/exclusion criteria. Therapeutic radiopharmaceuticals will be considered a prior line of systemic therapy. Main Exclusion Criteria: * Treatment with any radiopharmaceutical within 6 weeks of the first dose of Investigational Medicinal Product (IMP). * Radiation therapy (RT) or external beam radiation therapy (EBRT) within 28 days prior to the first dose and all RT-related events have not recovered to Grade ≤ 1. * Administration of any systemic cytotoxic or investigational therapy ≤ 28 days of the first dose of IMP or 5 half-lives, whichever is shorter. * All prior treatment-related adverse events must have resolved to Grade ≤ 1. * Concurrent severe and/or uncontrolled illness not related to cancer and/or social situation that would limit compliance with study requirements. * Known or suspected allergies or contraindications to any of the investigational drugs or any component of the investigational drug formulation. * Clinically relevant proteinuria * Diffuse and intense osseous radiotracer uptake on bone scintigraphy or PSMA imaging characteristic of a superscan. * Chronic corticosteroid use greater than 10 mg prednisone equivalent daily.