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

The main purpose of the study is to assess the safety and tolerability of AZD2284, AZD2287, and AZD2275.

This is a first-in-human, Phase I, non-randomized, open-label clinical trial designed to evaluate AZD2284, AZD2287, and AZD2275. This trial will consist of 2 Parts: Part A (Imaging): * Part A (Cold Antibody Exploration): aims to determine the optimal dosing regimen, with or without unconjugated antibody (AZD2275) pre-administration to improve the biodistribution of AZD2287. * Part A Expansion: aims to explore the prevalence of PSMA and STEAP2 expression by imaging. Part B (Therapeutic): * Part B (Actinium-225 Dose Escalation): aims to assess the safety, tolerability, and efficacy of escalating doses of AZD2284 informed by the optimal dosing regimen identified in Part A. * Part B Expansion Cohorts 1 and 2: aims to explore efficacy of AZD2284.

Main Inclusion Criteria: * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. * Histologically confirmed diagnosis of adenocarcinoma of the prostate or neuroendocrine differentiated prostate cancer. * 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 Main Exclusion Criteria: * Treatment with any radiopharmaceutical within 6 weeks of the first dose of Investigational Medicinal Product (IMP). * Radiation therapy (RT) 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