The intention of the study is to demonstrate superiority of AZD2265 relative to standard of care treatments by assessment of radiographic progression-free survival (rPFS) and overall survival (OS) in participants with mCRPC.
Approximately 670 adult participants with mCRPC will be randomized to receive either AZD2265 or standard of care treatment (investigator's choice of cabazitaxel, ARPI, or radium-223). They will receive their assigned treatment until disease progression, unacceptable toxicity, or other discontinuation criteria are met. Tumor evaluation scans will continue after treatment discontinuation until radiographically confirmed progression or death. All patients will be followed for survival until the end of the study. An Independent Data Monitoring Committee (IDMC) composed of independent experts will be convened to monitor the safety and scientific integrity of the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
670
IV in combination with oral prednisone/prednisolone
Oral in combination with prednisone/prednisolone
Radiographic Progression-Free Survival (rPFS)
rPFS is defined as the time from randomisation to radiographic progression, as assessed by the BICR per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone), or death due to any cause.
Time frame: From randomization until first radiographic progression per RECIST 1.1/PCWG3 by BICR, or death from any cause, whichever occurs first (up to approximately 33 months)
Overall Survival (OS)
OS is defined as the length of time from randomisation until the date of death due to any cause.
Time frame: From randomization until death from any cause (up to approximately 33 months)
Progression-Free Survival (PFS)
PFS is defined as the time from randomisation to the earliest of progression (defined as radiographic progression assessed by BICR per RECIST 1.1 and/or PCWG3 criteria, clinical progression, or PSA progression), or death due to any cause.
Time frame: From randomization until first documented progression (radiographic, clinical, or PSA progression) or death in the absence of progression, whichever occurs first (up to approximately 33 months)
Assessment of PSA50 (≥50% prostate-specific antigen reduction)
Proportion of participants achieving a \>= 50% decrease in PSA from baseline.
Time frame: From C1D1, assessed each treatment cycle then every 8 weeks after EOT until BICR-assessed radiographic progression per RECIST 1.1/PCWG3 (up to approximately 33 months)
Assessment of PSA90 (≥90% prostate-specific antigen reduction)
Proportion of participants achieving \>=90% decrease in PSA from baseline.
Time frame: From C1D1, assessed each treatment cycle then every 8 weeks after EOT until BICR-assessed radiographic progression per RECIST 1.1/PCWG3 (up to approximately 33 months)
AstraZeneca Clinical Study Information Center
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Oral
Oral; Available only to participants randomized under Protocol Version 2.0; not offered to participants randomized under Protocol Version 3.0 (04 June 2026)
Oral; Available only to participants randomized under Protocol Version 2.0; not offered to participants randomized under Protocol Version 3.0 (04 June 2026)
Oral; available in China only
IV
Research Site
Dothan, Alabama, United States
RECRUITINGResearch Site
Phoenix, Arizona, United States
NOT_YET_RECRUITINGResearch Site
Duarte, California, United States
NOT_YET_RECRUITINGResearch Site
Irvine, California, United States
NOT_YET_RECRUITINGResearch Site
Newport Beach, California, United States
RECRUITINGResearch Site
San Francisco, California, United States
NOT_YET_RECRUITINGResearch Site
Aurora, Colorado, United States
NOT_YET_RECRUITINGResearch Site
Miami, Florida, United States
RECRUITINGResearch Site
O'Fallon, Illinois, United States
NOT_YET_RECRUITINGResearch Site
Metairie, Louisiana, United States
RECRUITING...and 122 more locations
Objective Response Rate (ORR)
ORR is defined as the proportion of participants with measurable soft tissue disease at baseline who have a CR or PR as determined by BICR, per RECIST 1.1 (soft tissue) and PCWG3 criteria (bone).
Time frame: From baseline; assessed by BICR per RECIST 1.1/PCWG3 every 8 weeks for first 32 weeks, then every 12 weeks until radiographic progression (up to approximately 33 months)
Duration of Response (DoR)
DoR is defined as the time from the date of first documented response until date of documented progression per RECIST 1.1 (soft tissue) and/or PCWG3 criteria (bone) as determined by BICR or death in the absence of disease progression.
Time frame: From first documented response until progression per RECIST 1.1/PCWG3 by BICR, or death in the absence of progression, whichever occurs first (up to approximately 33 months)
Symptomatic Skeletal Event-Free Survival (SSE-FS)
SSE-FS is defined as the time from randomisation to the earliest of the following: * Use of radiation therapy to prevent or relieve skeletal symptoms. * Occurrence of new symptomatic pathological bone fractures (vertebral or non-vertebral). * Occurrence of spinal cord compression. * Orthopaedic surgical intervention for bone metastasis. * Death due to any cause.
Time frame: From randomization until first symptomatic skeletal event or death from any cause, whichever occurs first (up to approximately 33 months)
Plasma concentrations of AZD2265
Plasma concentrations of AZD2265 pre-dose and post-dose.
Time frame: Pre-dose and post-dose on Day 1 of Cycles 1 and 2; 3-24 hours post-dose on Cycle 1 Day 1 only (up to approximately 7 weeks)