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

NCT06879041 | Recruiting Phase 1 FDA Drug

• 1 other identifier: D7580C00001
• Study Type: interventional
• Target: 95
• Locations: 3 countries
• Sites: 15

Brief Summary

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

Conditions

Metastatic Castration-Resistant Prostate Cancer

Keywords

Dose Escalation Study; Metastatic Prostate Cancer; Radiopharmaceutical; Radiotheranostics; Castration-Resistant Prostate Cancer; Radiotherapy; Six Transmembrane Epithelial Antigen of the Prostate 2 (STEAP2); Actinium; Radioconjugate; Radioligand

Outcome Measures

Primary Outcomes (6)

• Number of participants with adverse event (AEs)

  Part A: From Screening (Day -28) to Day 28; Part B: Screening (Day -42 to Day -14) up to 5 years

• Number of participants with Dose Limiting Toxicities (DLTs)

  Part B: Screening (Day -42 to Day -14) up to 2 cycles (84 days) of AZD2284

• Estimates of residence time

  Part A: Up to Day 8 after dosing with AZD2287 on Day 1

• Absorbed radiation doses for AZD2287 and AZD2284

  Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14

• Compare organ uptake of AZD2287 with and without pre-dose administration of AZD2275

  Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14

• Tumor uptake of AZD2287 in selected regions of interest on SPECT/CT and/or planar images

  Part A: Up to Day 8 after dosing with AZD2287 on Day 1; Part B: Up to Day 8 after dosing with AZD2287 on Day -14

Secondary Outcomes (13)

• Overall Response Rate (ORR)

  Up to 12 months after the last dose of AZD2284

• Proportion of participants with Prostate-Specific Antigen (PSA) 50

  Up to 12 months after the last dose of AZD2284

• Proportion of participants with PSA90

  Up to 12 months after the last dose of AZD2284

• Time to maximum PSA % decline

  Up to 12 months after the last dose of AZD2284

• Duration of Response (DoR)

  Up to 12 months after the last dose of AZD2284

Study Arms (10)

Part A: Cohort A1: AZD2287 (Hot only)

EXPERIMENTAL

Participants will receive 1 dose of AZD2287. If eligible for treatment, will receive low dose of AZD2284.

Drug: AZD2287; Drug: AZD2284

Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot)

EXPERIMENTAL

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; Drug: AZD2275; Drug: AZD2284

Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot)

EXPERIMENTAL

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; Drug: AZD2275; Drug: AZD2284

Part A Expansion: AZD2287 + AZD2275 (Cold + Hot)

EXPERIMENTAL

Participants will receive dose of AZD2275 determined earlier in the study followed by 1 dose of AZD2287.

Drug: AZD2287; Drug: AZD2275

Part B (Actinium-225 Dose Escalation): low dose: AZD2284

EXPERIMENTAL

Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive low dose of AZD2284.

Drug: AZD2287; Drug: AZD2275; Drug: AZD2284

Part B (Actinium-225 Dose Escalation): medium dose: AZD2284

EXPERIMENTAL

Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive medium dose of AZD2284.

Drug: AZD2287; Drug: AZD2275; Drug: AZD2284

Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284

EXPERIMENTAL

Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284.

Drug: AZD2287; Drug: AZD2275; Drug: AZD2284

Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284

EXPERIMENTAL

Participants will receive AZD2287 (± AZD2275 as determined in Part A). If eligible for treatment, will receive high dose of AZD2284.

Drug: AZD2287; Drug: AZD2275; Drug: AZD2284

Part B: Cohort E1

EXPERIMENTAL

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; Drug: AZD2275; Drug: AZD2284

Part B: Cohort E2

EXPERIMENTAL

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; Drug: AZD2275; Drug: AZD2284

Interventions

AZD2287 DRUG

AZD2287 is administered through intravenous injection.

Part A Expansion: AZD2287 + AZD2275 (Cold + Hot); Part A: Cohort A1: AZD2287 (Hot only); Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot); Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot); Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284; Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284; Part B (Actinium-225 Dose Escalation): low dose: AZD2284; Part B (Actinium-225 Dose Escalation): medium dose: AZD2284; Part B: Cohort E1; Part B: Cohort E2

AZD2275 DRUG

AZD2275 is administered through intravenous infusion.

Part A Expansion: AZD2287 + AZD2275 (Cold + Hot); Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot); Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot); Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284; Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284; Part B (Actinium-225 Dose Escalation): low dose: AZD2284; Part B (Actinium-225 Dose Escalation): medium dose: AZD2284; Part B: Cohort E1; Part B: Cohort E2

AZD2284 DRUG

AZD2284 is administered through intravenous injection.

Part A: Cohort A1: AZD2287 (Hot only); Part A: Cohort A2: AZD2275 + AZD2287 (Cold +Hot); Part A: Cohort A3: AZD2275 + AZD2287 (Cold +Hot); Part B (Actinium-225 Dose Escalation): high dose 1: AZD2284; Part B (Actinium-225 Dose Escalation): high dose 2: AZD2284; Part B (Actinium-225 Dose Escalation): low dose: AZD2284; Part B (Actinium-225 Dose Escalation): medium dose: AZD2284; Part B: Cohort E1; Part B: Cohort E2

Eligibility Criteria

• Age: 18 Years+
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• AstraZeneca: lead
• Parexel: collaborator

Study Sites (15)

Research Site

Palo Alto, California, 94304, United States

NOT YET RECRUITING

Research Site

Miami, Florida, 33165, United States

RECRUITING

Research Site

Tampa, Florida, 33612, United States

RECRUITING

Research Site

Chicago, Illinois, 60637, United States

RECRUITING

Research Site

Metairie, Louisiana, 70006, United States

NOT YET RECRUITING

Research Site

Boston, Massachusetts, 02215, United States

RECRUITING

Research Site

Rochester, Minnesota, 55902, United States

NOT YET RECRUITING

Research Site

Omaha, Nebraska, 68130, United States

RECRUITING

Research Site

New York, New York, 10032, United States

NOT YET RECRUITING

Research Site

Cleveland, Ohio, 44195, United States

NOT YET RECRUITING

Research Site

Portland, Oregon, 97239, United States

NOT YET RECRUITING

Research Site

East Melbourne, 3002, Australia

RECRUITING

Research Site

CapeTown, 7925, South Africa

NOT YET RECRUITING

Research Site

Durban, 4013, South Africa

WITHDRAWN

Research Site

Pretoria, 181, South Africa

NOT YET RECRUITING

MeSH Terms

Conditions

Prostatic Neoplasms

Condition Hierarchy (Ancestors)

Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Prostatic Diseases; Male Urogenital Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 11, 2025
• First Posted: March 17, 2025
• Study Start: March 10, 2025
• Primary Completion (Estimated): April 16, 2029
• Study Completion (Estimated): April 16, 2029
• Last Updated: March 17, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment athttps://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

AU (1); ZA (3); US (11)