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RecruitingInterventionalPhase 3

A Phase III, Multicentre, Randomised Controlled Study to Evaluate the Efficacy and Safety of AZD2265 (FPI-2265) ²²⁵Ac-PSMA-I&T Compared With Standard of Care in Patients With PSMA-positive Metastatic Castration-resistant Prostate Cancer (VECTRA-01)

NCT ID: NCT07611110Sponsor: AstraZenecaLast updated: 2026-05-28

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.

Arms & 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

Outcome measures

Primary

  • 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)

Secondary

  • Progression-Free Survival (PFS)

    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)

    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)

    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)

  • Objective Response Rate (ORR)

    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)

    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)

    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

    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)

Eligibility criteria

Sex: MaleAge: 18 Years and olderHealthy 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.

Study locations (24)

Research Site

Dothan, Alabama, 36303

Not Yet Recruiting

Research Site

Phoenix, Arizona, 85004

Not Yet Recruiting

Research Site

Irvine, California, 92618

Not Yet Recruiting

Research Site

Loma Linda, California, 92354

Not Yet Recruiting

Research Site

San Francisco, California, 94143

Not Yet Recruiting

Research Site

Aurora, Colorado, 80045

Not Yet Recruiting

Research Site

Miami, Florida, 33165

Recruiting

Research Site

O'Fallon, Illinois, 62269

Not Yet Recruiting

Research Site

Metairie, Louisiana, 70006

Not Yet Recruiting

Research Site

Detroit, Michigan, 48201

Not Yet Recruiting

Research Site

Grand Rapids, Michigan, 49503

Not Yet Recruiting

Research Site

Omaha, Nebraska, 68130

Recruiting

Research Site

Omaha, Nebraska, 68130

Not Yet Recruiting

Research Site

Albuquerque, New Mexico, 87109

Not Yet Recruiting

Research Site

New Hyde Park, New York, 11042

Not Yet Recruiting

Research Site

New York, New York, 10065

Not Yet Recruiting

Research Site

Cleveland, Ohio, 44195

Not Yet Recruiting

Research Site

Dayton, Ohio, 45415

Not Yet Recruiting

Research Site

Portland, Oregon, 97239

Not Yet Recruiting

Research Site

Pittsburgh, Pennsylvania, 15232

Not Yet Recruiting

Research Site

Myrtle Beach, South Carolina, 29572

Not Yet Recruiting

Research Site

Nashville, Tennessee, 37203

Not Yet Recruiting

Research Site

Houston, Texas, 77042

Not Yet Recruiting

Research Site

Salt Lake City, Utah, 84106

Not Yet Recruiting