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

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

Overview

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).

Interventions

• Drug AZD2265 (FPI-2265)
  AZD2265 (FPI-2265) will be administered as an intravenous (IV) injection.
• Drug AZD9574
  AZD9574 will be administered orally.
• Drug Docetaxel
  Docetaxel will be administered as an IV infusion.
• Drug AZD2287 (Imaging agent)
  AZD2287 will be administered as an IV injection.

Primary outcome measures

• 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]
• 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)]
• Part B: Number of participants with TEAEs [Time frame: Up to approximately 1 year after last dose]
• Part B: Prostate Specific Antigen 50 (PSA50) response rate [Time frame: Up to 3 years 4 months]

Secondary outcome measures (12)

• 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]

Eligibility criteria

Inclusion criteria

• 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.

Inclusion Criteria for Sub study 1:

• 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.

Exclusion criteria

• 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.

Exclusion Criteria for Sub study 1:

• 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 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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 10 centers

• Research Site — Encino
• Research Site — South Pasadena
• Research Site — Miami
• Research Site — Tampa
• Research Site — Metairie
• Research Site — Minneapolis
• Research Site — Omaha
• Research Site — New York
• … and 2 more centers

Italy · 5 centers

• Research Site — Bergamo
• Research Site — Meldola
• Research Site — Milan
• Research Site — Milan
• Research Site — Roma

South Korea · 5 centers

• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul
• Research Site — Seoul

Spain · 5 centers

• Research Site — Barcelona
• Research Site — L'Hospitalet de Llobregat
• Research Site — Madrid
• Research Site — Madrid
• Research Site — Pamplona

United Kingdom · 5 centers

• Research Site — Fulham
• Research Site — Guildford
• Research Site — London
• Research Site — Newcastle upon Tyne
• Research Site — Oxford

Germany · 4 centers

• Research Site — Essen
• Research Site — Jena
• Research Site — Rostock
• Research Site — Tübingen

Australia · 1 center

• Research Site — North Adelaide

Identifiers

NCT: NCT07590934 · D7642C00001 · 2025-524920-23

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗