AZD2265 Compared With Standard of Care in PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)

AstraZeneca

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Castration-resistant Prostate Cancer

Treatments: Drug: Abiraterone; Drug: Rezvilutamide; Drug: Cabazitaxel; Drug: Radium-223; Drug: Apalutamide; Drug: Darolutamide; Drug: Enzalutamide; Drug: AZD2265

Study type: Interventional

Funder types: Industry

Identifiers

NCT07611110

D9735C00001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 670 estimated patients

Sex: Male

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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670 participants in 2 patient groups

Arm A

Experimental group

Description:

AZD2265

Treatment:

Drug: AZD2265

Arm B

Active Comparator group

Description:

Investigator's choice of cabazitaxel, ARPI switch, or radium-223

Treatment:

Drug: Enzalutamide

Drug: Darolutamide

Drug: Radium-223

Drug: Apalutamide

Drug: Rezvilutamide

Drug: Cabazitaxel

Drug: Abiraterone