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

Purpose

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

Condition

Metastatic Castration-Resistant Prostate Cancer

Eligibility

Eligible Ages: Over 18 Years
Eligible Genders: Male
Accepts Healthy Volunteers: No

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

Study Design

Phase: Phase 1
Study Type: Interventional
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Primary Purpose: Treatment
Masking: None (Open Label)

Arm Groups

Arm	Description	Assigned Intervention
Experimental Part A: Cohort A1: AZD2287 (Hot only)	Participants will receive 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot)	Participants will receive low dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot)	Participants will receive medium dose of AZD2275 followed by 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part A Expansion: AZD2287 + AZD2275 (Cold + Hot)	Participants will receive dose of AZD2275 determined earlier in the study followed by 1 dose of AZD2287.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion.
Experimental Part B (Actinium-225 Dose Escalation): low dose: AZD2284	Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part B (Actinium-225 Dose Escalation): medium dose: AZD2284	Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284	Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284	Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part B: Cohort E1	Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.
Experimental Part B: Cohort E2	Participants will receive dose of AZD2284 determined by the earlier results. Expansion cohort may be opened to further characterize the safety and efficacy of the dose level.	Drug: AZD2287 AZD2287 is administered through intravenous injection. Drug: AZD2275 AZD2275 is administered through intravenous infusion. Drug: AZD2284 AZD2284 is administered through intravenous injection.

Recruiting Locations

Research Site
Miami, Florida 33165

Research Site
Omaha, Nebraska 68130

More Details

NCT ID: NCT06879041
Status: Recruiting
Sponsor: AstraZeneca

Study Contact

AstraZeneca Clinical Study Information Center
1-877-240-9479
information.center@astrazeneca.com

Detailed Description

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.