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

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)

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.

Study Overview

• Status: Recruiting
• Conditions: Metastatic Castration-resistant Prostate Cancer
• Intervention / Treatment: Drug: Enzalutamide; Drug: Darolutamide; Drug: AZD2265; Drug: Cabazitaxel; Drug: Abiraterone; Drug: Apalutamide; Drug: Rezvilutamide; Drug: Radium-223

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.

• Study Type: Interventional
• Enrollment (Estimated): 670
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: AstraZeneca Clinical Study Information Center; Phone Number: 1-877-240-9479; Email: information.center@astrazeneca.com

Study Locations

• Australia
  • Darlinghurst, Australia, 2010
    • Not yet recruiting
    • Research Site
  • Melbourne, Australia, 3000
    • Not yet recruiting
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• Austria
  • Linz, Austria, 4020
    • Not yet recruiting
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  • Salzburg, Austria, 5020
    • Not yet recruiting
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• Brazil
  • São Paulo, Brazil, 05652-900
    • Not yet recruiting
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  • São Paulo, Brazil, 01308-050
    • Not yet recruiting
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• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • Not yet recruiting
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  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 1V7
      • Not yet recruiting
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  • Ontario
    • Hamilton, Ontario, Canada, L8V 1C3
      • Not yet recruiting
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    • Toronto, Ontario, Canada, M4N 3M5
      • Not yet recruiting
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  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Not yet recruiting
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    • Montreal, Quebec, Canada, H3A 1A1
      • Not yet recruiting
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• China
  • Beijing, China, 100034
    • Not yet recruiting
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  • Chengdu, China, 610041
    • Not yet recruiting
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  • Chongqing, China, 400030
    • Not yet recruiting
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  • Fuzhou, China, 350005
    • Not yet recruiting
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  • Guangzhou, China, 510060
    • Not yet recruiting
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  • Guangzhou, China, 510630
    • Not yet recruiting
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  • Guangzhou, China, 510120
    • Not yet recruiting
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  • Nanjing, China, 210029
    • Not yet recruiting
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  • Nanjing, China, 210006
    • Not yet recruiting
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  • Shanghai, China, 200032
    • Not yet recruiting
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  • Shanghai, China, 200025
    • Not yet recruiting
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  • Wuhan, China, 430022
    • Not yet recruiting
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  • Wuhan, China, 430030
    • Not yet recruiting
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• France
  • Villejuif, France, 94800
    • Not yet recruiting
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• Germany
  • Berlin, Germany, 13353
    • Not yet recruiting
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  • Bonn, Germany, 53127
    • Not yet recruiting
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  • Dresden, Germany, 01307
    • Not yet recruiting
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  • Essen, Germany, 45122
    • Not yet recruiting
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  • Karlsruhe, Germany, 76133
    • Not yet recruiting
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  • Münster, Germany, 48149
    • Not yet recruiting
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  • Rostock, Germany, 18057
    • Not yet recruiting
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  • Tübingen, Germany, 72076
    • Not yet recruiting
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  • Würzburg, Germany, 97080
    • Not yet recruiting
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• India
  • Bangalore, India, 560017
    • Not yet recruiting
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  • Gurgaon, India, 122002
    • Not yet recruiting
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  • Gurgaon, India, 122001
    • Not yet recruiting
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  • Navi Mumbai, India, 410210
    • Not yet recruiting
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• Japan
  • Fukuoka, Japan, 812-8582
    • Not yet recruiting
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  • Kanazawa, Japan, 920-8641
    • Not yet recruiting
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  • Kashiwa, Japan, 227-8577
    • Not yet recruiting
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  • Sapporo, Japan, 060-8638
    • Not yet recruiting
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• South Korea
  • Goyang-si, South Korea, 10408
    • Not yet recruiting
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  • Seoul, South Korea, 3722
    • Not yet recruiting
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  • Seoul, South Korea, 5505
    • Not yet recruiting
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• Spain
  • Barcelona, Spain, 8035
    • Not yet recruiting
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  • Barcelona, Spain, 08025
    • Not yet recruiting
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  • L'Hospitalet de Llobregat, Spain, 08908
    • Not yet recruiting
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  • Madrid, Spain, 28041
    • Not yet recruiting
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  • Málaga, Spain, 29009
    • Not yet recruiting
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  • Santiago de Compostela, Spain, 15706
    • Not yet recruiting
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• Taiwan
  • Kaohsiung City, Taiwan, 833401
    • Not yet recruiting
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  • Taipei, Taiwan, 11259
    • Not yet recruiting
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  • Taipei, Taiwan, 10002
    • Not yet recruiting
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  • Taipei, Taiwan, 11217
    • Not yet recruiting
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  • Taoyuan, Taiwan, 333
    • Not yet recruiting
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• Thailand
  • Bangkok, Thailand, 10700
    • Not yet recruiting
    • Research Site
  • Bangkok, Thailand, 10210
    • Not yet recruiting
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• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06530
    • Not yet recruiting
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  • Ankara, Turkey (Türkiye), 06620
    • Not yet recruiting
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  • Istanbul, Turkey (Türkiye), 34098
    • Not yet recruiting
    • Research Site
  • Istanbul, Turkey (Türkiye), 34752
    • Not yet recruiting
    • Research Site
• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Not yet recruiting
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  • Middlesbrough, United Kingdom, TS4 3BW
    • Not yet recruiting
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  • Southampton, United Kingdom, SO16 6YD
    • Not yet recruiting
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• United States
  • Alabama
    • Dothan, Alabama, United States, 36303
      • Not yet recruiting
      • Research Site
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Not yet recruiting
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  • California
    • Irvine, California, United States, 92618
      • Not yet recruiting
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    • Loma Linda, California, United States, 92354
      • Not yet recruiting
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    • San Francisco, California, United States, 94143
      • Not yet recruiting
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  • Colorado
    • Aurora, Colorado, United States, 80045
      • Not yet recruiting
      • Research Site
  • Florida
    • Miami, Florida, United States, 33165
      • Recruiting
      • Research Site
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • Not yet recruiting
      • Research Site
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Not yet recruiting
      • Research Site
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Not yet recruiting
      • Research Site
    • Grand Rapids, Michigan, United States, 49503
      • Not yet recruiting
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  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
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    • Omaha, Nebraska, United States, 68130
      • Not yet recruiting
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  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • Not yet recruiting
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  • New York
    • New Hyde Park, New York, United States, 11042
      • Not yet recruiting
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    • New York, New York, United States, 10065
      • Not yet recruiting
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  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Not yet recruiting
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    • Dayton, Ohio, United States, 45415
      • Not yet recruiting
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  • Oregon
    • Portland, Oregon, United States, 97239
      • Not yet recruiting
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  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Not yet recruiting
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  • South Carolina
    • Myrtle Beach, South Carolina, United States, 29572
      • Not yet recruiting
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  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Not yet recruiting
      • Research Site
  • Texas
    • Houston, Texas, United States, 77042
      • Not yet recruiting
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  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Not yet recruiting
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm A; AZD2265	Drug: AZD2265; IV; Other Names: FPI-2265
Active Comparator: Arm B; Investigator's choice of cabazitaxel, ARPI switch, or radium-223	Drug: Enzalutamide; Oral; Other Names: Xtandi; Drug: Darolutamide; Oral; Other Names: Nubeqa; Drug: Cabazitaxel; IV in combination with oral prednisone/prednisolone; Other Names: Jevtana; Drug: Abiraterone; Oral in combination with prednisone/prednisolone; Other Names: Zytiga; Drug: Apalutamide; Oral; Other Names: Erleada; Drug: Rezvilutamide; Oral; Other Names: Ariane; Drug: Radium-223; IV; Other Names: Xofigo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	From randomization until death from any cause (up to approximately 33 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	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.	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)	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).	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.	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.	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.	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)

Collaborators and Investigators

• Sponsor: AstraZeneca

Study record dates

Study Major Dates

• Study Start (Actual): May 4, 2026
• Primary Completion (Estimated): February 13, 2029
• Study Completion (Estimated): December 20, 2029

Study Registration Dates

• First Submitted: April 22, 2026
• First Submitted That Met QC Criteria: May 20, 2026
• First Posted (Actual): May 28, 2026

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: AZD2265; prostate cancer; mCRPC; PSMA; FPI-2265; 225Ac
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Genital Neoplasms, Male; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Genital Diseases, Male; Prostatic Diseases; Male Urogenital Diseases; Prostatic Neoplasms; Polycyclic Compounds; Steroids; Fused-Ring Compounds; Androstenes; Androstanes; Abiraterone Acetate; darolutamide; abiraterone; enzalutamide; cabazitaxel; Radium-223; apalutamide; radium Ra 223 dichloride
• Other Study ID Numbers: D9735C00001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Access Criteria: When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool. Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No