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NCT07590934PHASE1, PHASE2Recruiting

Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer

AstraZeneca

Start Date

6/3/2026

Completion Date

9/25/2029

Summary

The purpose of the study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of multiple anti-cancer agents in participants with metastatic prostate cancer.

Detailed Description

This is a multicentre, open-label and platform study to evaluate multiple anti-cancer agents in participants with metastatic prostate cancer. This platform study will comprise a series of substudies. Each substudy will follow a 2-part structure (unless otherwise stated in the individual substudy): * Part A: A dose escalation (DE) phase to identify dose limiting toxicities (DLTs), characterise safety, PK, pharmacodynamics, preliminary efficacy, and determine biologically and clinically suitable dose levels to proceed into the dose optimisation/expansion. * Part B: A dose optimisation/expansion phase to inform recommended Phase 3 dose (RP3D), explore efficacy with Prostate-specific antigen (PSA) decrease ≥ 50% (PSA50) rate as primary endpoints, alongside continued safety monitoring. Sub-study 1 focuses on a specific combination regimen and it will assess the safety, tolerability, PK, pharmacodynamics, and preliminary anti-tumour activity of AZD2265 (FPI-2265) in combination with AZD9574 compared with AZD2265 (FPI-2265) monotherapy and with standard-of-care (SoC) docetaxel chemotherapy in participants with metastatic castration resistant prostate cancer (mCRPC).

Eligibility Criteria

Age Range: 18 years to 99 years

Inclusion Criteria: 1. Participants with a diagnosis of histologically confirmed adenocarcinoma of the prostate (no small cell, neuroendocrine, sarcomatoid, spindle or signet cell). 2. Minimum life expectancy of 3 months or more. 3. Eastern Cooperative Oncology Group (ECOG) performance status of O or 1 at screening, with no deterioration. 4. PCWG3 (Prostate Cancer Working Group 3) modified RECIST Version 1.1 evaluable disease. 5. Must have received at least one novel androgen receptor pathway inhibitor (ARPI), such as enzalutamide or darolutamide or apalutamide or abiraterone acetate. 6. Must have one or more unresectable metastatic lesions. 7. Must have had prior orchiectomy and/or ongoing androgen deprivation therapy, and a castrate level of serum testosterone (\<50ng/dL or \<l.7nmol/L). 8. Progressive metastatic castration-resistant prostate cancer (mCRPC) following the most recent treatment at time of study entry. 9. Adequate organ and marrow function. 10. Non sterilised participants who are sexually active with a partner of childbearing potential must use a condom (plus spermicide, if available), must refrain from fathering a child, freezing or donating sperm, and it is recommended for the partner to also use a highly effective contraceptive method. Inclusion Criteria for Sub study 1: 1. Must have received a single line of ARPI, such as enzalutamide, darolutamide, apalutamide or abiraterone acetate. 2. PSMA positive mCRPC by computed tomography positron emission tomography, obtained with PSMA ligand defined as at least 1 PSMA positive metastatic lesion with tracer uptake greater than liver, and no PSMA negative lesions. All measurable or intraprostatic lesions must be PSMA positive. 3. Capable of self-administering oral formulations. Exclusion Criteria: 1. Any evidence of non adenocarcinomatous forms of prostate cancer (including small cell, spindle cell, signet cell, neuroendocrine, sarcomatous). 2. Known, unresolved urinary tract obstruction. 3. Participants with a history of central nervous system metastases. 4. Symptomatic malignant spinal cord compression or findings indicative of impending cord compression. 5. Participants with a history of leptomeningeal carcinomatosis. 6. Previous or concurrent cancer distinct from the cancer under investigation in primary site or histology . 7. Concurrent serious medical conditions. 8. Previous history of interstitial lung disease or non-infectious pneumonitis. 9. Participants with a history or clinical/laboratory features suggestive of myelodysplastic syndrome or acute myeloid leukaemia. 10. Persistent toxicities caused by previous therapy. 11. Participants unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with absorption. 12. Active infection, including tuberculosis, hepatitis C virus, and hepatitis B virus infection. 13. Known hypersensitivity to study intervention or any of their excipients. Exclusion Criteria for Sub study 1: 1. History of uncontrolled seizures or requirement for \>2 antiepileptic drugs. 2. History of severe brain injury or stroke. 3. Skeletal metastases demonstrating a superscan appearance on bone scan. 4. Participants have received prior therapy with AZD9574 or more than 1 prior line of any other Poly-ADP-ribose polymerase inhibitor (PARPi)-based regimen (either as a treatment or as maintenance).

Interventions

DRUG

AZD2265 (FPI-2265)

DRUG

AZD9574

DRUG

Docetaxel

DRUG

AZD2287 (Imaging agent)

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Conditions

Metastatic Prostate Cancer

Locations

Research Site

Encino, California 91436

United States

Research Site

South Pasadena, California 91030

United States

Research Site

Miami, Florida 33165

United States

Research Site

Tampa, Florida 33612

United States

Research Site

Metairie, Louisiana 70006

United States

Research Site

Minneapolis, Minnesota 55455

United States

Research Site

Omaha, Nebraska 68130

United States

Research Site

New York, New York 10065

United States

Research Site

Portland, Oregon 97239

United States

Research Site

Houston, Texas 77030

United States

Research Site

North Adelaide, 5000

Australia

Research Site

Essen, 45147

Germany

Research Site

Jena, 07747

Germany

Research Site

Rostock, 18057

Germany

Research Site

Tübingen, 72076

Germany

Research Site

Bergamo, 24127

Italy

Research Site

Meldola, 47014

Italy

Research Site

Milan, 20133

Italy

Research Site

Milan, 20141

Italy

Research Site

Roma, 00168

Italy

Research Site

Seoul, 03080

South Korea

Research Site

Seoul, 03722

South Korea

Research Site

Seoul, 06351

South Korea

Research Site

Seoul, 06591

South Korea

Research Site

Seoul, 5505

South Korea

Research Site

Barcelona, 08028

Spain

Research Site

L'Hospitalet de Llobregat, 08908

Spain

Research Site

Madrid, 28031

Spain

Research Site

Madrid, 28041

Spain

Research Site

Pamplona, 31008

Spain

Research Site

Fulham, SW3 6JJ

United Kingdom

Research Site

Guildford, CU2 7XX

United Kingdom

Research Site

London, WC1E 6DB

United Kingdom

Research Site

Newcastle upon Tyne, NE7 7DN

United Kingdom

Research Site

Oxford, OX3 7LE

United Kingdom