Safety and Efficacy Study of Safusidenib in Participants With Grade 2 IDH1-Mutant Glioma

Официальное название

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study to Evaluate the Efficacy and Safety of Safusidenib in Participants With Grade 2 Isocitrate Dehydrogenase 1 (IDH1)-Mutant Glioma

Обзор

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study comparing the efficacy and safety of safusidenib versus placebo in participants with residual or recurrent Grade 2 glioma (oligodendroglioma or astrocytoma) with an IDH1 mutation who have undergone surgery as their only treatment and are not in need of immediate chemotherapy or radiotherapy.

Вмешательства

• Препарат Safusidenib
  Safusidenib administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment until disease progression or another reason for discontinuation occurs.
• Препарат Placebo
  Placebo administered twice daily as a single agent dosed orally on Days 1 through 28 of a 28-day cycle. Participants may continue treatment with placebo until disease progression or another reason for discontinuation occurs.

Первичные конечные точки

• Progression Free Survival (PFS) assessed by Blinded Independent Central Review (BICR) per modified Response Assessment in Neuro-Oncology (RANO) 2.0 [Срок оценки: From the date of randomization until the date of first documented disease progression, approximately 30 months]

Вторичные конечные точки (12)

• Objective Response Rate (ORR) assessed by BICR per modified RANO 2.0 [Срок оценки: From the date of randomization until the date of first documented disease progression, approximately 30 months]
• Time to Next Intervention (TTNI) [Срок оценки: From the date of randomization until the date of the start of another anticancer treatment or date of death, approximately 30 months]
• PFS assessed by the Investigator per modified RANO 2.0 [Срок оценки: From the date of randomization until the date of first documented disease progression, approximately 30 months]
• ORR assessed by the Investigator per modified RANO 2.0 [Срок оценки: From the date of randomization until the date of the first documented disease progression, approximately 30 months]
• Duration of Response (DOR) assessed by BICR and by the Investigator per modified RANO 2.0 [Срок оценки: From the date of randomization until the date of first documented disease progression, approximately 30 months]
• Time to Response (TTR) assessed by BICR and by the Investigator per modified RANO 2.0 [Срок оценки: From randomization to the first documentation of objective response (CR, PR, or MR), approximately 30 months]
• Disease Control Rate (DCR) assessed by BICR and by the Investigator per modified RANO 2.0 [Срок оценки: From the date of randomization until the date of first documented disease progression, approximately 30 months]
• Tumor Growth Rate (TGR) by volume assessed by BICR [Срок оценки: From historical scans through the final scan in the study, approximately 30 months]
• Overall Survival (OS) [Срок оценки: From the date of randomization until the date of death, approximately 30 months]
• Safety and tolerability [Срок оценки: From the first dose of study drug until 30 days after treatment discontinuation, approximately 30 months]
• Safusidenib PK Profile [Срок оценки: From the first dose of study drug through approximately 16 weeks]
• Health-Related Quality of Life [Срок оценки: From the first dose of study drug to treatment discontinuation, approximately 30 months]

Критерии участия

Критерии включения

• Expected survival of ≥12 months.
• At least 1 prior surgery for glioma (biopsy, sub-total resection, or gross total resection), with the most recent surgery having occurred at least 90 days (or at least 28 days if biopsy only and postoperative changes have resolved per BICR) and no longer than 5 years before the date of randomization
• Have not had any other prior anticancer therapy, including chemotherapy and radiotherapy; and are not in need of immediate chemotherapy or radiotherapy in the opinion of the Investigator.
• Histologically confirmed Grade 2, IDH1-mutant oligodendroglioma or astrocytoma according to World Health Organization Central Nervous System 2021 classification criteria per Investigator assessment.
• IDH1 mutation (R132H/C/G/S/L), identified by polymerase chain reaction, next-generation sequencing (NGS), or immunohistochemistry; and confirmed 1p19q codeletion status by fluorescence in situ hybridization, NGS, or array comparative genomic hybridization.
• Residual or recurrent, measurable, non-enhancing disease, as confirmed by BICR per RANO 2.0, assessed at Screening.
• Adequate hematologic and organ functions

Критерии исключения

• Any prior anticancer therapy other than surgery (biopsy, sub-total, or gross total resection) for treatment of glioma, including chemotherapy, investigational therapies, prior therapies targeting IDH1 or IDH2, anti-angiogenic therapies, tumor-treating fields, or radiotherapy.
• High-risk features as assessed by the Investigator, including brainstem or spinal cord involvement either as primary location or by significant tumor extension, clinically relevant functional or neurocognitive deficits due to the tumor (deficits resulting from surgery are allowed), or uncontrolled seizures (defined as persistent seizures interfering with ability to comply with protocol requirements).
• Evidence of leptomeningeal disease.
• Use of therapeutic doses of steroids for signs/symptoms of glioma. Participants taking physiologic doses (defined as equivalent of <1.5 mg of dexamethasone equivalent) for medical conditions not related to glioma will be permitted.

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

Четверное слепое

Основная цель

Лечение

Центры проведения

Список центров уточняется — проверьте первичный протокол.

Идентификаторы

NCT: NCT07712757 · NUV-218-G307

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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