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

A Phase Ib/II, Open-label, Multi-centre, Platform Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Multiple Anti-Cancer Agents in Metastatic Prostate Cancer

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Metastatic Prostate Cancer
• Intervention / Treatment: Drug: AZD9574; Drug: AZD2265 (FPI-2265); Drug: AZD2287 (Imaging agent); Drug: Docetaxel

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).

• Study Type: Interventional
• Enrollment (Estimated): 152
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • North Adelaide, Australia, 5000
    • Research Site
• Germany
  • Essen, Germany, 45147
    • Research Site
  • Rostock, Germany, 18057
    • Research Site
  • Tübingen, Germany, 72076
    • Research Site
• Italy
  • Bergamo, Italy, 24127
    • Research Site
  • Meldola, Italy, 47014
    • Research Site
  • Milan, Italy, 20141
    • Research Site
  • Milan, Italy, 20133
    • Research Site
  • Roma, Italy, 00168
    • Research Site
• South Korea
  • Seoul, South Korea, 03080
    • Research Site
  • Seoul, South Korea, 03722
    • Research Site
  • Seoul, South Korea, 06351
    • Research Site
  • Seoul, South Korea, 06591
    • Research Site
  • Seoul, South Korea, 5505
    • Research Site
• Spain
  • Barcelona, Spain, 08028
    • Research Site
  • L'Hospitalet de Llobregat, Spain, 08908
    • Research Site
  • Madrid, Spain, 28031
    • Research Site
  • Madrid, Spain, 28041
    • Research Site
  • Pamplona, Spain, 31008
    • Research Site
• United Kingdom
  • Fulham, United Kingdom, SW3 6JJ
    • Research Site
  • Guildford, United Kingdom, CU2 7XX
    • Research Site
  • London, United Kingdom, WC1E 6DB
    • Research Site
  • Newcastle upon Tyne, United Kingdom, NE7 7DN
    • Research Site
  • Oxford, United Kingdom, OX3 7LE
    • Research Site
• United States
  • California
    • Encino, California, United States, 91436
      • Research Site
    • South Pasadena, California, United States, 91030
      • Research Site
  • Florida
    • Miami, Florida, United States, 33165
      • Research Site
    • Tampa, Florida, United States, 33612
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Research Site
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Research Site
  • New York
    • New York, New York, United States, 10065
      • Research Site
  • Oregon
    • Portland, Oregon, United States, 97239
      • Research Site
  • Texas
    • Houston, Texas, United States, 77030
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sub study 1 Part A (SS1A): escalating dose levels of AZD9574 in combination with AZD2265 (FPI-2265); Participants will receive escalating dose levels of AZD9574 once daily in combination with AZD2265 (FPI-2265) once every 6 weeks (Q6W).	Drug: AZD9574; AZD9574 will be administered orally.; Drug: AZD2265 (FPI-2265); AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.; Other Names: FPI-2265; 225Ac-PSMA-I&T; Drug: AZD2287 (Imaging agent); AZD2287 will be administered as an IV injection.
Experimental: Sub study 1 Part B (SS1B): selected dose of AZD9574 in combination with AZD2265 (FPI-2265); Participants will receive AZD9574 chosen from the DE phase once daily in combination with AZD2265 (FPI-2265) Q6W.	Drug: AZD9574; AZD9574 will be administered orally.; Drug: AZD2265 (FPI-2265); AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.; Other Names: FPI-2265; 225Ac-PSMA-I&T; Drug: AZD2287 (Imaging agent); AZD2287 will be administered as an IV injection.
Experimental: SS1B: AZD2265 (FPI-2265) monotherapy; Participants will receive AZD2265 (FPI-2265) monotherapy Q6W.	Drug: AZD2265 (FPI-2265); AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.; Other Names: FPI-2265; 225Ac-PSMA-I&T; Drug: AZD2287 (Imaging agent); AZD2287 will be administered as an IV injection.
Active Comparator: SS1B: Docetaxel; Participants will receive docetaxel as a standard of care (SoC) once every 3 weeks (Q3W).	Drug: AZD2287 (Imaging agent); AZD2287 will be administered as an IV injection.; Drug: Docetaxel; Docetaxel will be administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part A and Part B: 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) (Part A) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B).	Up to 3 years 4 months
Part A and Part B: Prostate Specific Antigen 90 (PSA90) response rate	PSA90 response rate is defined as proportion of participants achieving a ≥ 90% 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. PSA90 will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	Up to 3 years 4 months
Part A and Part B: Time to PSA50 (TTPSA50) response	TTPSA50 response is defined as the time from date of randomisation/first dose of study intervention until the date of first documented PSA50 response (≥ 50% decrease in PSA from baseline), confirmed by a second consecutive PSA assessment at least 3 weeks later. TTPSA50 response will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: Time to PSA90 (TTPSA90) response	TTPSA90 response is defined as the time from date of randomisation/first dose of study intervention until the date of first documented PSA90 response (≥ 90% decrease in PSA from baseline, respectively), confirmed by a second consecutive PSA assessment at least 3 weeks later. TTPSA90 response will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: Duration of PSA50 (DoPSA50) response	DoPSA50 response is defined as the time from the date of first documented PSA50 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression. DoPSA50 response will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: Duration of PSA90 (DoPSA90) response	DoPSA90 response is defined as the time from the date of first documented PSA90 response, that is subsequently confirmed by a second consecutive PSA assessment at least 3 weeks later, until the date of documented PSA progression. DoPSA90 response will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: Time to PSA progression	TTPSA progression is defined as time from the date of randomisation/first dose of study intervention until the date of documented PSA progression or the last PSA result in the absence of progression. PSA progression is defined as an increase in PSA of ≥ 25% from the nadir and an absolute increase of at least 2 ng/mL above nadir beyond 12 weeks. PSA progression must be confirmed by a second value taken at least 3 weeks later. TTPSA progression will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: PSA over time	PSA over time is defined as the longitudinal change in serum PSA from baseline across all on-study timepoints. PSA over time will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	Up to 3 years 4 months
Part A and Part B: Radiographic Progression-free survival (rPFS)	rPFS is defined as the time from date of randomisation/first dose of study intervention until the date of objective disease progression according to response evaluation criteria in solid tumors (RECIST) 1.1 (for soft tissue disease) and prostate cancer working group 3 (PCWG3) criteria (for bone disease) as assessed by the investigator at the local site, or death (by any cause in the absence of progression), regardless of whether the participant withdraws from therapy or receives another anti-cancer therapy prior to progression. rPFS will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	From Day 1 to 3 years 4 months
Part A and Part B: Overall Response Rate (ORR)	The ORR is defined as the percentage of participants who have a confirmed complete response (CR) or confirmed partial response (PR), as the time from the date of first documented objective response (which is subsequently confirmed) until the date of radiographic disease progression or censored according to rules for rPFS. The ORR will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	From Day 1 to 3 years 4 months
Part A and Part B: Best Overall Response (BOR)	The BOR is defined as the best overall visit response the participant achieves as determined by the investigator at the local site. The BOR will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	From Day 1 to 3 years 4 months
Part A and Part B: Duration of response (DoR)	The DoR is defined based on RECIST 1.1 (for soft tissue disease) and PCWG3 criteria (for bone disease) as the time from the date of first documented objective response (which is subsequently confirmed) until date of radiographic disease progression or censored according to rules for rPFS. The DoR will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	From Day 1 to 3 years 4 months
Part A and Part B: Time to Response (TTR)	The TTR is defined as the time from the date of randomisation/first dose of study intervention until the date of first documented objective response, which is subsequently confirmed. The TTR will be assessed to check the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + AZD9574 relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).	From Day 1 to 3 years 4 months
Part A and Part B: Percentage change in tumour size	To assess the anti-tumour activity of AZD9574 in combination with AZD2265 (FPI-2265).	From Day 1 to 3 years 4 months
Part A and Part B: Plasma concentration of AZD9574	To determine the PK of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle will be 42 days)
Part A and Part B: Plasma concentration of AZD2265 (FPI-2265)	To determine the PK of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 1 (each cycle will be 42 days)
Part A and Part B: Area under the concentration time curve (AUC)	To determine the PK (AUC) of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle will be 42 days)
Part A and Part B: Maximum observed drug concentration (Cmax)	To determine the PK (Cmax) of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle will be 42 days)
Part A and Part B: Time to reach Cmax (tmax)	To determine the PK (tmax) of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle will be 42 days)
Part A and Part B: Terminal elimination half-life (t½λz)	To determine the PK (t½λz) of AZD9574 in combination with AZD2265 (FPI-2265).	From Cycle 1 Day 1 to Cycle 2 Day 15 (each cycle will be 42 days)
Part A and Part B: Change from baseline in study-specific biomarker ABC in response to treatment	To investigate pharmacodynamics of AZD9574 in combination with AZD2265 (FPI-2265) (for Part A and Part B) and of AZD2265 (FPI-2265) monotherapy (for Part B only).	Up to 3 years 4 months
Part A and Part B: Change from baseline in study-specific biomarker XYZ in response to treatment	To investigate study-specific XYZ expression and relationship to response to the treatment.	Up to 3 years 4 months

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Estimated): May 14, 2026
• Primary Completion (Estimated): September 5, 2029
• Study Completion (Estimated): September 5, 2029

Study Registration Dates

• First Submitted: May 11, 2026
• First Submitted That Met QC Criteria: May 11, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 15, 2026
• Last Update Submitted That Met QC Criteria: May 11, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Metastatic castration resistant prostate cancer; Combination therapy; Prostate-specific membrane antigen-targeted radioligand therapy; Alpha particle therapy; Poly ADP-ribose polymerase 1 (PARP1) inhibitor therapy; Docetaxel therapy
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Taxoids; Cyclodecanes; Diterpenes; Docetaxel
• Other Study ID Numbers: D7642C00001; 2025-524920-23 (Other Identifier: EU CT number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

• IPD Sharing 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.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No