Metastatic Castration-resistant Prostate Cancer
Conditions
Keywords
AZD2265; prostate cancer; mCRPC; PSMA; FPI-2265; 225Ac
Brief summary
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.
Detailed description
Approximately 670 adult participants with mCRPC will be randomized to receive either AZD2265 or standard of care treatment (investigator's choice of cabazitaxel, ARPI switch, 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.
Interventions
DRUGAZD2265
IV
DRUGCabazitaxel
IV in combination with oral prednisone/prednisolone
DRUGAbiraterone
Oral in combination with prednisone/prednisolone
DRUGEnzalutamide
Oral
DRUGApalutamide
Oral
DRUGDarolutamide
Oral
DRUGRezvilutamide
Oral
DRUGRadium-223
IV
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Open-label
Intervention model description
Participants are randomized to receive either AZD2265 or standard of care treatment (investigator's choice of cabazitaxel, ARPI switch, or radium-223).
Eligibility
Sex/Gender
MALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years of age. * Diagnosis of adenocarcinoma of prostate. * Must have had prior orchiectomy and/or ongoing ADT and a castrate level of plasma/serum testosterone. * Progressive mCRPC following the most recent treatment at the time of study entry, with at least 1 metastatic lesion (measurable and/or non-measurable) that is suitable for repeated assessment by CT and/or MRI and/or bone scan. * Previously treated with at least 2 cycles of PSMA-directed β-emitting radioconjugate. * Previously treated with at least 1 taxane-based chemotherapy regimen for either metastatic hormone-sensitive prostate cancer or CRPC. * Previously treated with at least 1 ARPI (eg, enzalutamide, abiraterone, etc.). * Positive PSMA PET/CT scans, obtained with PSMA ligands (⁶⁸Ga-PSMA-11 or ¹⁸F-DCFPyL). * ECOG performance status of 0 to 2. * Adequate organ and bone marrow function as described in study protocol. * Participants must not father children or donate sperm from signing ICF, during the study intervention and for 6 months after the last dose of study intervention. * Participants must use a condom from signing ICF, during study intervention, and for 6 months after the last dose of study drug, with all sexual partners.
Exclusion criteria
* Prior treatment with an α-emitting molecular targeted therapeutic radioconjugate (prior treatment with radium-223 is permitted). * Progression on PSMA-directed β-emitting radioconjugate prior to the administration of Cycle 3. * Receipt of \> 6 cycles of PSMA-directed β-emitting therapeutic RC. * History of another primary malignancy, with exceptions. * Persistent toxicities (CTCAE Grade ≥ 2) caused by previous anticancer therapy, with exceptions. * Spinal cord compression or brain metastases unless asymptomatic, stable, and not requiring steroids for at least 4 weeks prior to start of study intervention. * Clinically significant ECG abnormalities, with exceptions.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Radiographic Progression-Free Survival (rPFS) | 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) | 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. |
| Overall Survival (OS) | From randomization until death from any cause (up to approximately 33 months) | OS is defined as the length of time from randomisation until the date of death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of PSA50 (≥50% prostate-specific antigen reduction) | 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) | Proportion of participants achieving a \>= 50% decrease in PSA from baseline. |
| Assessment of PSA90 (≥90% prostate-specific antigen reduction) | 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) | Proportion of participants achieving \>=90% decrease in PSA from baseline. |
| Objective Response Rate (ORR) | 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) | 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), in the absence of progression by PCWG3 criteria (bone). |
| Symptomatic Skeletal Event-Free Survival (SSE-FS) | From randomization until first symptomatic skeletal event or death from any cause, whichever occurs first (up to approximately 33 months) | 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. |
| Duration of Response (DoR) | 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) | 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. |
| Plasma concentrations of AZD2265 | 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) | Plasma concentrations of AZD2265 pre-dose and post-dose. |
| Progression-Free Survival (PFS) | 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) | 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. |
Countries
Australia, Austria, Brazil, Canada, China, France, Germany, India, Japan, South Korea, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed