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

NCT07590934 · AstraZeneca
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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
About this study
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
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 design
Enrollment target: 152 participants
Allocation: randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2026-06-03
Estimated completion: 2029-09-25
Last updated: 2026-06-30
Interventions
Drug: AZD2265 (FPI-2265)Drug: AZD9574Drug: DocetaxelDrug: AZD2287 (Imaging agent)
Primary outcomes
  • 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) (Up to approximately 1 year after last dose)
  • Part A: Number of participants with dose limiting toxicities (DLTs) (From date of first dose up to approximately 2 cycles (up to 3 months))
  • Part B: Number of participants with TEAEs (Up to approximately 1 year after last dose)
Sponsor
AstraZeneca · industry
Contacts & investigators
ContactAstraZeneca Clinical Study Information Center · contact · information.center@astrazeneca.com · 1-877-240-9479
All locations (35)
Research SiteNot Yet Recruiting
Encino, California, United States
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South Pasadena, California, United States
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Miami, Florida, United States
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Tampa, Florida, United States
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Metairie, Louisiana, United States
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Minneapolis, Minnesota, United States
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Omaha, Nebraska, United States
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New York, New York, United States
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Portland, Oregon, United States
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Houston, Texas, United States
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North Adelaide, Australia
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Essen, Germany
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Jena, Germany
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Rostock, Germany
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Tübingen, Germany
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Bergamo, Italy
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Meldola, Italy
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Milan, Italy
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Milan, Italy
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Roma, Italy
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Seoul, South Korea
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Barcelona, Spain
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L'Hospitalet de Llobregat, Spain
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Madrid, Spain
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Madrid, Spain
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Pamplona, Spain
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Fulham, United Kingdom
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Guildford, United Kingdom
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London, United Kingdom
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Newcastle upon Tyne, United Kingdom
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Oxford, United Kingdom
Phase Ib/II Platform Study of Multiple Anti-Cancer Agents in Participants With Metastatic Prostate Cancer · TrialPath