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

Official title

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)

Overview

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

• Drug AZD2265
  IV
• Drug Cabazitaxel
  IV in combination with oral prednisone/prednisolone
• Drug Abiraterone
  Oral in combination with prednisone/prednisolone
• Drug Enzalutamide
  Oral
• Drug Apalutamide
  Oral
• Drug Darolutamide
  Oral
• Drug Rezvilutamide
  Oral
• Drug Radium-223
  IV

Primary outcome measures

• Radiographic Progression-Free Survival (rPFS) [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) [Time frame: From randomization until death from any cause (up to approximately 33 months)]

Secondary outcome measures (7)

• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Single blind

Primary purpose

Treatment

Study locations

United States · 25 centers

• Research Site — Dothan
• Research Site — Phoenix
• Research Site — Duarte
• Research Site — Irvine
• Research Site — Newport Beach
• Research Site — San Francisco
• Research Site — Aurora
• Research Site — Miami
• … and 17 more centers

China · 17 centers

• Research Site — Beijing
• Research Site — Beijing
• Research Site — Chengdu
• Research Site — Chongqing
• Research Site — Fuzhou
• Research Site — Guangzhou
• Research Site — Guangzhou
• Research Site — Guangzhou
• … and 9 more centers

Germany · 14 centers

• Research Site — Augsburg
• Research Site — Berlin
• Research Site — Bonn
• Research Site — Cologne
• Research Site — Dresden
• Research Site — Essen
• Research Site — Jena
• Research Site — Karlsruhe
• … and 6 more centers

Canada · 7 centers

• Research Site — Edmonton
• Research Site — Halifax
• Research Site — Hamilton
• Research Site — Toronto
• Research Site — Toronto
• Research Site — Montreal
• Research Site — Montreal

Spain · 7 centers

Center list to be confirmed — check the primary protocol.

Taiwan · 5 centers

Center list to be confirmed — check the primary protocol.

India · 4 centers

• Research Site — Bangalore
• Research Site — Gurgaon
• Research Site — Gurgaon
• Research Site — Navi Mumbai

Japan · 4 centers

• Research Site — Fukuoka
• Research Site — Kanazawa
• Research Site — Kashiwa
• Research Site — Sapporo

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

South Korea · 3 centers

• Research Site — Goyang-si
• Research Site — Seoul
• … and 1 more center

United Kingdom · 3 centers

Center list to be confirmed — check the primary protocol.

Australia · 2 centers

• Research Site — Darlinghurst
• Research Site — Melbourne

Austria · 2 centers

• Research Site — Linz
• Research Site — Salzburg

Brazil · 2 centers

• Research Site — São Paulo
• Research Site — São Paulo

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Thailand · 2 centers

Center list to be confirmed — check the primary protocol.

France · 1 center

• Research Site — Villejuif

Identifiers

NCT: NCT07611110 · D9735C00001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗