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

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

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

Первичные конечные точки

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

Вторичные конечные точки (7)

• Progression-Free Survival (PFS) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: From randomization until first symptomatic skeletal event or death from any cause, whichever occurs first (up to approximately 33 months)]
• Plasma concentrations of AZD2265 [Срок оценки: 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)]

Критерии участия

Критерии включения

• ≥ 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Простое слепое

Основная цель

Лечение

Центры проведения

США · 25 центров

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Китай · 17 центров

• Research Site — Пекин
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• Research Site — Гуанчжоу
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Германия · 14 центров

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Канада · 7 центров

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Испания · 7 центров

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Тайвань · 5 центров

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Индия · 4 центра

• Research Site — Bangalore
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Япония · 4 центра

• Research Site — Fukuoka
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Turkey (Türkiye) · 4 центра

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South Korea · 3 центра

• Research Site — Goyang-si
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Великобритания · 3 центра

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Австралия · 2 центра

• Research Site — Darlinghurst
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Австрия · 2 центра

• Research Site — Linz
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Бразилия · 2 центра

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

Швеция · 2 центра

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Таиланд · 2 центра

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Франция · 1 центр

• Research Site — Villejuif

Идентификаторы

NCT: NCT07611110 · D9735C00001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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