A Phase I clinical trial is currently underway to evaluate the safety, tolerability, and initial efficacy of three investigational agents—AZD2284, AZD2287, and AZD2275—in patients with metastatic castration-resistant prostate cancer (mCRPC). This non-randomized, open-label, first-in-human study aims to explore innovative approaches to imaging and targeted treatment.

The study is structured into two key parts:

Part A (Imaging Phase) consists of two components. First, the “Cold Antibody Exploration” segment is designed to determine the optimal dosing strategy for AZD2287, examining its performance with or without pre-administration of AZD2275, an unconjugated antibody. The goal is to enhance the biodistribution and effectiveness of AZD2287. The second component, “Part A Expansion,” focuses on assessing the prevalence of crucial biomarkers—Prostate-Specific Membrane Antigen (PSMA) and Six-Transmembrane Epithelial Antigen of Prostate 2 (STEAP2)—using advanced imaging techniques.

Part B (Therapeutic Phase) builds on findings from Part A. Initially, “Actinium-225 Dose Escalation” aims to determine the safety, tolerability, and preliminary efficacy of increasing doses of AZD2284, guided by dosing insights from the imaging studies. Following this, the “Part B Expansion Cohorts 1 and 2” will further evaluate the therapeutic efficacy of ²²⁵Ac-AZD2284 at identified optimal dosages.

Due to the innovative and exploratory nature of this trial, comprehensive data on AZD2284, AZD2287, and AZD2275 remain limited. Outcomes from this study will inform future research directions, potentially opening new avenues for the treatment of mCRPC.

NOTE: While it may be logical to hypothesize that simultaneous expression of both PSMA and STEAP2 biomarkers could be required to fully activate the molecule and enhance precision delivery, currently, this remains speculative

Clinical trial.