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

NCT07590934 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: D7642C000012025-524920-23
• Study Type: interventional
• Target: 152
• Locations: 7 countries
• Sites: 33

Brief 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.

Conditions

Metastatic Prostate Cancer

Keywords

Metastatic castration resistant prostate cancer; Prostate-specific membrane antigen-targeted radioligand therapy; Alpha particle therapy; Poly ADP-ribose polymerase 1 (PARP1) inhibitor therapy; Combination therapy; Docetaxel therapy

Outcome Measures

Primary Outcomes (4)

• Part A: Number of participants with treatment-emergent adverse events (TEAEs)including serious adverse events (SAEs), treatment-related AEs (TRAEs) and adverse events of special interests (AESIs)

  To assess the safety and tolerability of AZD9574 in combination with AZD2265 (FPI-2265).

  Up to approximately 1 year after last dose

• Part A: Number of participants with dose limiting toxicities (DLTs)

  To assess the safety and tolerability, and characterise the DLTs of AZD9574 in combination with AZD2265 (FPI-2265).

  From date of first dose up to approximately 2 cycles (up to 3 months)

• Part B: Number of participants with TEAEs

  To further assess the safety and tolerability, and determine the recommended Phase 3 dose (RP3D) of AZD9574 in combination with AZD2265 (FPI-2265).

  Up to approximately 1 year after last dose

• Part B: Prostate Specific Antigen 50 (PSA50) response rate

  PSA50 response rate is defined as proportion of participants achieving a ≥ 50% decrease in PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later, and occurring prior to confirmed PSA progression. PSA50 will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).

  Up to 3 years 4 months

Secondary Outcomes (22)

• Part A and Part B: PSA50 response rate

  Up to 3 years 4 months

• Part A and Part B: Prostate Specific Antigen 90 (PSA90) response rate

  Up to 3 years 4 months

• Part A and Part B: Time to PSA50 (TTPSA50) response

  Up to 3 years 4 months

• Part A and Part B: Time to PSA90 (TTPSA90) response

  Up to 3 years 4 months

• Part A and Part B: Duration of PSA50 (DoPSA50) response

  Up to 3 years 4 months

Study Arms (4)

Sub study 1 Part A (SS1A): escalating dose levels of AZD9574 in combination with AZD2265 (FPI-2265)

EXPERIMENTAL

Participants will receive escalating dose levels of AZD9574 once daily in combination with AZD2265 (FPI-2265) once every 6 weeks (Q6W).

Drug: AZD2265 (FPI-2265); Drug: AZD9574; Drug: AZD2287 (Imaging agent)

Sub study 1 Part B (SS1B): selected dose of AZD9574 in combination with AZD2265 (FPI-2265)

EXPERIMENTAL

Participants will receive AZD9574 chosen from the DE phase once daily in combination with AZD2265 (FPI-2265) Q6W.

Drug: AZD2265 (FPI-2265); Drug: AZD9574; Drug: AZD2287 (Imaging agent)

SS1B: AZD2265 (FPI-2265) monotherapy

EXPERIMENTAL

Participants will receive AZD2265 (FPI-2265) monotherapy Q6W.

Drug: AZD2265 (FPI-2265); Drug: AZD2287 (Imaging agent)

SS1B: Docetaxel

ACTIVE COMPARATOR

Participants will receive docetaxel as a standard of care (SoC) once every 3 weeks (Q3W).

Drug: Docetaxel; Drug: AZD2287 (Imaging agent)

Interventions

AZD2265 (FPI-2265) DRUG

AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.

Also known as: FPI-2265, 225Ac-PSMA-I&T

SS1B: AZD2265 (FPI-2265) monotherapy; Sub study 1 Part A (SS1A): escalating dose levels of AZD9574 in combination with AZD2265 (FPI-2265); Sub study 1 Part B (SS1B): selected dose of AZD9574 in combination with AZD2265 (FPI-2265)

AZD9574 DRUG

AZD9574 will be administered orally.

Sub study 1 Part A (SS1A): escalating dose levels of AZD9574 in combination with AZD2265 (FPI-2265); Sub study 1 Part B (SS1B): selected dose of AZD9574 in combination with AZD2265 (FPI-2265)

Docetaxel DRUG

Docetaxel will be administered as an IV infusion.

SS1B: Docetaxel

AZD2287 (Imaging agent) DRUG

AZD2287 will be administered as an IV injection.

SS1B: AZD2265 (FPI-2265) monotherapy; SS1B: Docetaxel; Sub study 1 Part A (SS1A): escalating dose levels of AZD9574 in combination with AZD2265 (FPI-2265); Sub study 1 Part B (SS1B): selected dose of AZD9574 in combination with AZD2265 (FPI-2265)

Eligibility Criteria

• Age: 18 Years - 99 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants with a diagnosis of histologically confirmed adenocarcinoma of the prostate (no small cell, neuroendocrine, sarcomatoid, spindle or signet cell).
• Minimum life expectancy of 3 months or more.
• Eastern Cooperative Oncology Group (ECOG) performance status of O or 1 at screening, with no deterioration.
• PCWG3 (Prostate Cancer Working Group 3) modified RECIST Version 1.1 evaluable disease.
• Must have received at least one novel androgen receptor pathway inhibitor (ARPI), such as enzalutamide or darolutamide or apalutamide or abiraterone acetate.
• Must have one or more unresectable metastatic lesions.
• Must have had prior orchiectomy and/or ongoing androgen deprivation therapy, and a castrate level of serum testosterone (\<50ng/dL or \<l.7nmol/L).
• Progressive metastatic castration-resistant prostate cancer (mCRPC) following the most recent treatment at time of study entry.
• Adequate organ and marrow function.
• 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.
• Must have received a single line of ARPI, such as enzalutamide, darolutamide, apalutamide or abiraterone acetate.
• 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.
• Capable of self-administering oral formulations.

You may not qualify if:

• Any evidence of non adenocarcinomatous forms of prostate cancer (including small cell, spindle cell, signet cell, neuroendocrine, sarcomatous).
• Known, unresolved urinary tract obstruction.
• Participants with a history of central nervous system metastases.
• Symptomatic malignant spinal cord compression or findings indicative of impending cord compression.
• Participants with a history of leptomeningeal carcinomatosis.
• Previous or concurrent cancer distinct from the cancer under investigation in primary site or histology .
• Concurrent serious medical conditions.
• Previous history of interstitial lung disease or non-infectious pneumonitis.
• Participants with a history or clinical/laboratory features suggestive of myelodysplastic syndrome or acute myeloid leukaemia.
• Persistent toxicities caused by previous therapy.
• Participants unable to swallow orally administered medications or with gastrointestinal disorders likely to interfere with absorption.
• Active infection, including tuberculosis, hepatitis C virus, and hepatitis B virus infection.
• Known hypersensitivity to study intervention or any of their excipients.
• History of uncontrolled seizures or requirement for \>2 antiepileptic drugs.
• History of severe brain injury or stroke.

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (33)

Research Site

Encino, California, 91436, United States

Location

Research Site

South Pasadena, California, 91030, United States

Location

Research Site

Miami, Florida, 33165, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Minneapolis, Minnesota, 55455, United States

Location

Research Site

Omaha, Nebraska, 68130, United States

Location

Research Site

New York, New York, 10065, United States

Location

Research Site

Portland, Oregon, 97239, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

North Adelaide, 5000, Australia

Location

Research Site

Essen, 45147, Germany

Location

Research Site

Rostock, 18057, Germany

Location

Research Site

Tübingen, 72076, Germany

Location

Research Site

Bergamo, 24127, Italy

Location

Research Site

Meldola, 47014, Italy

Location

Research Site

Milan, 20133, Italy

Location

Research Site

Milan, 20141, Italy

Location

Research Site

Roma, 00168, Italy

Location

Research Site

Seoul, 03080, South Korea

Location

Research Site

Seoul, 03722, South Korea

Location

Research Site

Seoul, 06351, South Korea

Location

Research Site

Seoul, 06591, South Korea

Location

Research Site

Seoul, 5505, South Korea

Location

Research Site

Barcelona, 08028, Spain

Location

Research Site

L'Hospitalet de Llobregat, 08908, Spain

Location

Research Site

Madrid, 28031, Spain

Location

Research Site

Madrid, 28041, Spain

Location

Research Site

Pamplona, 31008, Spain

Location

Research Site

Fulham, SW3 6JJ, United Kingdom

Location

Research Site

Guildford, CU2 7XX, United Kingdom

Location

Research Site

London, WC1E 6DB, United Kingdom

Location

Research Site

Newcastle upon Tyne, NE7 7DN, United Kingdom

Location

Research Site

Oxford, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Prostatic Neoplasms

Interventions

Docetaxel

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

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: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 11, 2026
• First Posted: May 15, 2026
• Study Start: May 14, 2026
• Primary Completion (Estimated): September 5, 2029
• Study Completion (Estimated): September 5, 2029
• Last Updated: May 15, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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 rerefer to our disclosure commitment at https://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. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

GB (5); DE (3); IT (5); US (9); ES (5); KR (5); AU (1)