Metastatic Prostate CancerPhase 1/2PROSPECTORNCT07590934
Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer
A Phase 1/2 study testing AZD2265 (FPI-2265), Palacaparib (AZD9574) and Docetaxel in people with Metastatic Prostate Cancer, run by AstraZeneca at 38 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 years, men only
- Conditions the study is for
- Metastatic Prostate Cancer
- What is being tested?
- AZD2265 (FPI-2265), Palacaparib (AZD9574) and Docetaxel
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 152 participants
- Where
- 38 sitesin 7 countries
- Study dates
- 3 Jun 2026to 25 Sep 2029
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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. Participants who were exposed to more than one ARPI due to toxicity or intolerance (not due to disease progression) are eligible.
- 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.
Who cannot join
- 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 .
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- 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.
- Skeletal metastases demonstrating a superscan appearance on bone scan.
- Participants have received prior therapy with palacaparib (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).
Trial locations and contacts
38 sites in 7 countries. Contact the study team or a site near you to ask about taking part.
AstraZeneca Clinical Study Information Center contact
38 sites in 7 countries
United States12 sites, 12 recruiting
- Not yet recruiting
Research Site
Duarte, California, 91010
- Not yet recruiting
Research Site
Encino, California, 91436
- Not yet recruiting
Research Site
Houston, Texas, 77030
- Not yet recruiting
Research Site
Metairie, Louisiana, 70006
- Recruiting
Research Site
Miami, Florida, 33165
- Not yet recruiting
Research Site
Minneapolis, Minnesota, 55455
- Not yet recruiting
Research Site
New York, New York, 10065
- Recruiting
Research Site
Omaha, Nebraska, 68130
- Not yet recruiting
Research Site
Orlando, Florida, 32806
- Not yet recruiting
Research Site
Portland, Oregon, 97239
- Recruiting
Research Site
South Pasadena, California, 91030
- Not yet recruiting
Research Site
Tampa, Florida, 33612
United Kingdom6 sites, 6 recruiting
- Not yet recruiting
Research Site
Belfast, BT9 7AB
- Not yet recruiting
Research Site
Fulham, SW3 6JJ
- Not yet recruiting
Research Site
Guildford, CU2 7XX
- Not yet recruiting
Research Site
London, WC1E 6DB
- Not yet recruiting
Research Site
Newcastle upon Tyne, NE7 7DN
- Not yet recruiting
Research Site
Oxford, OX3 7LE
Italy5 sites, 5 recruiting
- Not yet recruiting
Research Site
Bergamo, 24127
- Not yet recruiting
Research Site
Meldola, 47014
- Not yet recruiting
Research Site
Milan, 20133
- Not yet recruiting
Research Site
Milan, 20141
- Not yet recruiting
Research Site
Roma, 00168
South Korea5 sites, 4 recruiting
- Not yet recruiting
Research Site
Seoul, 03080
- Not yet recruiting
Research Site
Seoul, 03722
- Not yet recruiting
Research Site
Seoul, 06351
- Not yet recruiting
Research Site
Seoul, 06591
- Withdrawn
Research Site
Seoul, 5505
Spain5 sites, 5 recruiting
- Not yet recruiting
Research Site
Barcelona, 08028
- Not yet recruiting
Research Site
L'Hospitalet de Llobregat, 08908
- Not yet recruiting
Research Site
Madrid, 28031
- Not yet recruiting
Research Site
Madrid, 28041
- Not yet recruiting
Research Site
Pamplona, 31008
Germany4 sites, 4 recruiting
- Not yet recruiting
Research Site
Essen, 45147
- Not yet recruiting
Research Site
Jena, 07747
- Not yet recruiting
Research Site
Rostock, 18057
- Not yet recruiting
Research Site
Tübingen, 72076
Australia1 site, 1 recruiting
- Not yet recruiting
Research Site
North Adelaide, 5000
About this study
Official title: 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.
Read the 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) actinium (225Ac) zadavotide guraxetan [hereafter referred to as AZD2265 (FPI-2265)] in combination with palacaparib (AZD9574) compared with AZD2265 (FPI-2265) monotherapy and with standard-of-care (SoC) docetaxel chemotherapy in participants with metastatic castration resistant prostate cancer (mCRPC).
- Conditions
- Metastatic Prostate Cancer
- Being tested
- AZD2265 (FPI-2265), Palacaparib (AZD9574), Docetaxel, AZD2287 (Imaging agent)
- 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
- Medical subject headings
- Prostatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD2265 (FPI-2265)Drug
Also called FPI-2265, 225Ac-PSMA-I&T
AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.
Palacaparib (AZD9574)Drug
Palacaparib (AZD9574) will be administered orally.
DocetaxelDrug
Docetaxel will be administered as an IV infusion.
AZD2287 (Imaging agent)Drug
AZD2287 will be administered as an IV injection.
| Study group | Role | What they receive |
|---|---|---|
| Substudy 1 Part A(SS1A): escalating dose levels of palacaparib in combination with AZD2265(FPI-2265) | Experimental | Participants will receive escalating dose levels of palacaparib (AZD9574) once daily in combination with AZD2265 (FPI-2265) once every 6 weeks (Q6W). Receives: Drug: AZD2265 (FPI-2265); Drug: Palacaparib (AZD9574); Drug: AZD2287 (Imaging agent) |
| Sub study 1 Part B(SS1B): selected dose of palacaparib in combination with AZD2265(FPI-2265) | Experimental | Participants will receive palacaparib (AZD9574) chosen from the DE phase once daily in combination with AZD2265 (FPI-2265) Q6W. Receives: Drug: AZD2265 (FPI-2265); Drug: Palacaparib (AZD9574); Drug: AZD2287 (Imaging agent) |
| SS1B: AZD2265 (FPI-2265) monotherapy | Experimental | Participants will receive AZD2265 (FPI-2265) monotherapy Q6W. Receives: 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). Receives: Drug: Docetaxel; Drug: AZD2287 (Imaging agent) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: Up to 3 years 4 months
Secondary outcomes (23)
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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (Part A and Part B) and to demonstrate effectiveness of AZD2265 (FPI-2265) + palacaparib (AZD9574) relative to AZD2265 (FPI-2265) alone and relative to docetaxel (Part B only).
Measured: From Day 1 to 3 years 4 months
Part A: Disease control rate (DCR)
To assess the anti-tumour activity of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265)
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: From Day 1 to 3 years 4 months
Part A and Part B: Plasma concentration of palacaparib (AZD9574)
To determine the PK of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Measured: 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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265) (for Part A and Part B) and of AZD2265 (FPI-2265) monotherapy (for Part B only).
Measured: 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.
Measured: Up to 3 years 4 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 May 2026
- Study start3 Jun 2026
- Primary completion25 Sep 2029 (estimated)
- Study completion25 Sep 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Prostate CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 152 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07590934
- Sponsor's protocol ID
- D7642C00001
- Other IDs
- 2025-524920-23, 2025
- Acronym
- PROSPECTOR
- Status last verified
- Oct 2026
- First submitted
- 11 May 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07590934
- Acronym / sponsor ID
- PROSPECTOR / D7642C00001
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 152 participants (estimated)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 3 Jun 2026 (actual)
- Primary completion
- 25 Sep 2029 (estimated)
- Study completion
- 25 Sep 2029 (estimated)
- First posted
- 15 May 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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) actinium (225Ac) zadavotide guraxetan [hereafter referred to as AZD2265 (FPI-2265)] in combination with palacaparib (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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Substudy 1 Part A(SS1A): escalating dose levels of palacaparib in combination with AZD2265(FPI-2265) | Experimental | Drug: AZD2265 (FPI-2265), Drug: Palacaparib (AZD9574), Drug: AZD2287 (Imaging agent)Participants will receive escalating dose levels of palacaparib (AZD9574) once daily in combination with AZD2265 (FPI-2265) once every 6 weeks (Q6W). |
| Sub study 1 Part B(SS1B): selected dose of palacaparib in combination with AZD2265(FPI-2265) | Experimental | Drug: AZD2265 (FPI-2265), Drug: Palacaparib (AZD9574), Drug: AZD2287 (Imaging agent)Participants will receive palacaparib (AZD9574) chosen from the DE phase once daily in combination with AZD2265 (FPI-2265) Q6W. |
| SS1B: AZD2265 (FPI-2265) monotherapy | Experimental | Drug: AZD2265 (FPI-2265), Drug: AZD2287 (Imaging agent)Participants will receive AZD2265 (FPI-2265) monotherapy Q6W. |
| SS1B: Docetaxel | Active comparator | Drug: Docetaxel, Drug: AZD2287 (Imaging agent)Participants will receive docetaxel as a standard of care (SoC) once every 3 weeks (Q3W). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (17 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD2265 (FPI-2265)Also: FPI-2265, 225Ac-PSMA-I&TAZD2265 (FPI-2265) will be administered as an intravenous (IV) injection. | Drug | SS1B: AZD2265 (FPI-2265) monotherapy, Sub study 1 Part B(SS1B): selected dose of palacaparib in combination with AZD2265(FPI-2265), Substudy 1 Part A(SS1A): escalating dose levels of palacaparib in combination with AZD2265(FPI-2265) |
| Palacaparib (AZD9574)Palacaparib (AZD9574) will be administered orally. | Drug | Sub study 1 Part B(SS1B): selected dose of palacaparib in combination with AZD2265(FPI-2265), Substudy 1 Part A(SS1A): escalating dose levels of palacaparib in combination with AZD2265(FPI-2265) |
| DocetaxelDocetaxel will be administered as an IV infusion. | Drug | SS1B: Docetaxel |
| AZD2287 (Imaging agent)AZD2287 will be administered as an IV injection. | Drug | SS1B: AZD2265 (FPI-2265) monotherapy, SS1B: Docetaxel, Sub study 1 Part B(SS1B): selected dose of palacaparib in combination with AZD2265(FPI-2265), Substudy 1 Part A(SS1A): escalating dose levels of palacaparib in combination with AZD2265(FPI-2265) |
Primary outcome
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)
Time frame: Up to approximately 1 year after last dose
To assess the safety and tolerability of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part A: Number of participants with dose limiting toxicities (DLTs)
Time frame: From date of first dose up to approximately 2 cycles (up to 3 months)
To assess the safety and tolerability, and characterise the DLTs of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part B: Number of participants with TEAEs
Time frame: Up to approximately 1 year after last dose
To further assess the safety and tolerability, and determine the recommended Phase 3 dose (RP3D) of palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
Part B: Prostate Specific Antigen 50 (PSA50) response rate
Time frame: Up to 3 years 4 months
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 palacaparib (AZD9574) in combination with AZD2265 (FPI-2265).
23 secondary outcomes
Part A and Part B: PSA50 response rate
Time frame: Up to 3 years 4 months
Part A and Part B: Prostate Specific Antigen 90 (PSA90) response rate
Time frame: Up to 3 years 4 months
Part A and Part B: Time to PSA50 (TTPSA50) response
Time frame: Up to 3 years 4 months
Part A and Part B: Time to PSA90 (TTPSA90) response
Time frame: Up to 3 years 4 months
Part A and Part B: Duration of PSA50 (DoPSA50) response
Time frame: Up to 3 years 4 months
Part A and Part B: Duration of PSA90 (DoPSA90) response
Time frame: Up to 3 years 4 months
Part A and Part B: Time to PSA progression
Time frame: Up to 3 years 4 months
Part A and Part B: PSA over time
Time frame: Up to 3 years 4 months
Part A and Part B: Radiographic Progression-free survival (rPFS)
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Overall Response Rate (ORR)
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Best Overall Response (BOR)
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Duration of response (DoR)
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Time to Response (TTR)
Time frame: From Day 1 to 3 years 4 months
Part A: Disease control rate (DCR)
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Percentage change in tumour size
Time frame: From Day 1 to 3 years 4 months
Part A and Part B: Plasma concentration of palacaparib (AZD9574)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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)
Time frame: 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
Time frame: Up to 3 years 4 months
Part A and Part B: Change from baseline in study-specific biomarker XYZ in response to treatment
Time frame: Up to 3 years 4 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Oct 2026.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
AstraZeneca Clinical Study Information Center contact
38 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD2265 (FPI-2265), Palacaparib (AZD9574) and Docetaxel in people with Metastatic Prostate Cancer, run by AstraZeneca at 38 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 38 sites in United States, United Kingdom, Italy, South Korea, Spain and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact AstraZeneca Clinical Study Information Center (1-877-240-9479, information.center@astrazeneca.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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) (time frame: Up to approximately 1 year after last dose). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Oct 2026.