Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5500 (AMX-500) in Prostate Cancer

Официальное название

A Phase 1, First-in-Human Study of the Safety, Pharmacokinetics, and Preliminary Efficacy of VIR-5500 (AMX-500) in Participants With Prostate Cancer

Обзор

The study will be conducted in 4 parts and will commence with dose escalation of VIR-5500 as a monotherapy (Part 1), followed by combination escalation (Part 3a), monotherapy dose expansion (Part 2) and combination dose expansion (Part 4a). * Part 1 (Monotherapy Dose Escalation): Single-agent VIR-5500 dose escalation * Part 2 (Monotherapy Dose Expansion): Single-agent VIR-5500 dose expansion * Part 3 (Combination Dose Escalation): VIR-5500 plus another therapeutic agent dose escalation Part 3a (Combination Dose Escalation): VIR-5500 in combination with an androgen receptor signaling inhibitor (ARSI) * Part 4 (Combination Dose Expansion): VIR-5500 plus another therapeutic agent dose expansion Part 4a (Combination Dose Expansion): VIR-5500 in combination with an androgen receptor signaling inhibitor (ARSI)

Подробное описание

Duration of the study up to approximately 48 months.

Вмешательства

• Препарат VIR-5500
  Pharmaceutical form: Solution for infusion Route of administration: Intravenous (IV) infusion
• Комбинированный продукт ARSI
  Oral administration

Первичные конечные точки

• Part 1 and 3a: Number of participants with treatment-emergent Adverse Events (AEs) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• Part 1 and 3a: Incidence of Dose Limiting Toxicities (DLTs) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to Day 21 or Day 28]
• Part 2 and 4a: Prostate-Specific Antigen (PSA) response rate [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• Part 2 and 4a: Objective Response Rate (ORR) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]

Вторичные конечные точки (10)

• Part 2 and 4a: Number of participants with Adverse Events (AEs) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• Part 1 and 3a: PSA response rate [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• Part 1 and 3a: Objective Response Rate (ORR) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Duration of response (DoR) [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Progression Free Survival PFS [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Assessment of PK parameters: Cmax [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Assessment of PK parameters: AUC [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Assessment of PK parameters: Tmax [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Incidence of baseline anti-drug antibodies (ADAs) to VIR-5500 [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]
• All parts: Incidence of treatment emergent anti-drug antibodies (ADAs) to VIR-5500 [Срок оценки: from the Cycle 1(each cycle is 21 or 28 days), Day 1 up to approximately 48 months]

Критерии участия

Критерии включения

Applicable to Parts 1 and 2

• Have metastatic disease, defined by ≥ 1 metastatic lesion that is present on baseline computed tomography (CT), magnetic resonance imaging (MRI), or bone scan imaging
• Have documented progressive mCRPC based on ≥ 1 of the criteria (per PCWG3)

• PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
• Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
• Appearance of ≥ 2 new lesions in bone scan
• Have been treated with ≥ 1 second-generation androgen-signaling inhibitor, including abiraterone, apalutamide, darolutamide, and/or enzalutamide
• Have been treated with ≥ 1 prior taxane regimens (e.g., docetaxel, cabazitaxel)
• Are deemed unsuitable for standard of care

Applicable to Part 2, 3a and Part 4a,

• Have metastatic CRPC, defined by ≥ 1 metastatic lesion that is present on baseline CT, MRI, or bone scan imaging that has documented progressive disease (PD) based on ≥ 1 of the following criteria (per PCWG3):

• PSA level ≥ 1 ng/mL that has increased on ≥ 2 successive occasions ≥ 1 week apart
• Nodal or visceral progression as defined by RECIST v1.1 with PCWG3 modifications
• Appearance of ≥2 new lesions in bone scan
• Participants with metastatic hormone sensitive prostate cancer (mHSPC) or with biochemical recurrent prostate cancer (BRPC) may also participate in select cohorts of this clinical trial.

Критерии исключения

• Presence of dominant histopathological features representative of sarcomatoid, spindle cell, or neuroendocrine small cell components
• Has acute or chronic infections
• Has a concomitant medical or inflammatory condition that may increase the risk of toxicity to VIR-5500 (AMX-500), per the Investigator
• Has lesions in proximity of vital organs
• Has known active CNS metastases and/or carcinomatous meningitis The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Испания · 5 центров

• Investigational Site Number: 251 — Barcelona
• Investigational Site Number: 250 — Barcelona
• Investigational Site Number: 254 — Madrid
• Investigational Site Number: 252 — Madrid
• Investigational Site Number: 253 — Pamplona

США · 4 центра

• Investigational Site Number: 403 — Palo Alto
• Investigational Site Number: 401 — Houston
• Investigational Site number: 404 — Fairfax
• Investigational Site Number: 400 — Seattle

Австралия · 2 центра

• Investigational Site Number: 100 — Melbourne
• Investigational Site Number: 101 — Sydney

Великобритания · 1 центр

• Investigational Site Number: 300 — London

Идентификаторы

NCT: NCT05997615 · VIR-5500-V101 · U1111-1287-6968 · 2023-503495-24 · AMX-500

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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