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.
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).
Eligibility
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 \
