Study of Oral MRT-2359 With Apalutamide in Prostate Cancer

Официальное название

MODeFIRe-1 (Molecular Degrader for Inhibitor Resistance): A Phase 2, Open-Label, Multicenter Study of Oral MRT-2359 in Combination With Apalutamide in Patients With Castration-Resistant Prostate Cancer

Обзор

This Phase 2, open-label, multicenter study is conducted in patients with castration-resistant prostate cancer. Patients in this study receive MRT-2359, an investigational oral medicine, in combination with apalutamide, an oral medicine used to treat prostate cancer. The main purpose of the study is to assess whether this treatment combination can lower prostate-specific antigen (PSA) The study will also evaluate the safety and tolerability of the treatment combination and assess additional measures of anti-tumor activity.

Подробное описание

This Phase 2, open-label, multicenter study is designed to assess the efficacy, safety, tolerability, pharmacokinetic (PK), pharmacodynamic (PD), and clinical activity of MRT-2359 in combination with apalutamide in patients with castration-resistant prostate cancer.

The primary aim of the study is to assess the PSA response rate of MRT-2359 in combination with apalutamide as determined by PCWG4 criteria.

Secondary aims include further evaluation of safety and tolerability, additional measures of anti-tumor activity, and characterization of the PK profile of MRT-2359 in combination with apalutamide.

Вмешательства

• Препарат Oral MRT-2359
  Orally administered tablets of MRT-2359
• Препарат Apalutamide
  Orally administered apalutamide

Первичные конечные точки

• Assess the efficacy of MRT-2359 combined with apalutamide [Срок оценки: 14 months]

Вторичные конечные точки (11)

• Further evaluation of the safety and tolerability of MRT-2359 administered orally in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To assess additional measures of the efficacy of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]
• To characterize the population pharmacokinetic profile of MRT-2359 in combination with apalutamide [Срок оценки: 20 months]

Критерии участия

Критерии включения

• Age > 18 years
• A predicted life expectancy of ≥ 3 months and an ECOG performance status ≤ 1
• Have histologically or cytologically confirmed castration-resistant adenocarcinoma of the prostate without small cell histology and with androgen receptor (AR) mutations
• Have not had prior treatment with more than 1 prior taxane-based chemotherapy regimen for castration-resistant prostate cancer
• Have no prior treatment with an AR degrader, opevesostat, or similar therapy
• Has ongoing (chemical or surgical) androgen deprivation with serum testosterone < 50 ng/dL (< 1.7 nM)
• Has received prior treatment with poly(ADP-ribose) polymerase (PARP) inhibitor, if appropriate, or deemed ineligible to receive treatment by the Investigator, or has refused PARP inhibitor treatment
• Has received prior treatment with at least 1 line of ARPi
• Have disease measurable per Prostate Cancer Working Group 4 (PCWG4) criteria, with or without measurable disease by RECIST 1.1
• Be able to provide a tumor biopsy for biomarker analysis during the Screening period
• Have adequate organ function

Критерии исключения

• • Have received prior chemotherapy, definitive radiation, or biological cancer therapy within 21 days before the first dose of study treatment or have any AEs that have failed to recover to baseline

• Have received prior therapy with a GSPT1 degrader that was discontinued due to an AE
• Have received prior auto-HCT and have not fully recovered from effects of the last transplant
• Have received allogeneic hematopoietic stem cell transplantation within past 6 months and/or have symptoms of graft-versus-host disease
• Current use of chronic systemic steroid therapy in excess of replacement doses
• Have clinically active central nervous system involvement and/or carcinomatous meningitis
• Have a confirmed history of (noninfectious) pneumonitis that required steroids
• Clinically significant cardiac disease

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 14 центров

• START Los Angeles — Los Angeles
• Hoag Memorial Hospital Presbyterian — Newport Beach
• Rocky Mountain Cancer Center — Colorado Springs
• Kansas University Cancer Center — Kansas City
• University of Maryland Greenebaum Cancer Center — Baltimore
• Henry Ford — Novi
• XCancer Omaha — Omaha
• START New Jersey — East Brunswick
• … и ещё 6 центров

Идентификаторы

NCT: NCT07745361 · MRT-2359-002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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