A Study to Evaluate Tovorafenib in Pediatric and Young Adult Participants With Relapsed or Progressive Low-Grade Glioma and Advance Solid Tumors

Официальное название

FIREFLY-1: A Phase 2, Open-Label, Multicenter Study to Evaluate the Safety and Efficacy of the Oral Pan-RAF Inhibitor DAY101 in Pediatric Patients With RAF-Altered, Recurrent or Progressive Low-Grade Glioma and Advanced Solid Tumors

Обзор

This is a Phase 2, multi center, open-label study to evaluate the safety and efficacy of Type II RAF (tovorafenib) in pediatric participants with low-grade glioma or advanced solid tumors. Qualifying genomic alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories prior to enrollment into any of the arms. The study will consist of a screening period, a treatment period, a long-term extension phase, end of treatment (EOT) visit(s), a safety follow-up visit, and long-term follow-up assessments.

Вмешательства

• Препарат Tovorafenib
  Tovorafenib is an oral Type II RAF kinase inhibitor available in 100 mg immediate-release tablet or 25 mg/milliliter (mL) powder for reconstitution.

Первичные конечные точки

• Arm 1: Overall response rate [Срок оценки: Up to 48 months]
• Arm 2: Number of participants reporting adverse events [Срок оценки: Up to 48 months]
• Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters [Срок оценки: Up to 48 months]
• Arm 2: Number of participants with clinically significant changes in hematology parameters [Срок оценки: Up to 48 months]
• Arm 3: Overall response rate [Срок оценки: Up to 48 months]

Вторичные конечные точки (12)

• Arm 1 and 3: Number of participants reporting adverse events [Срок оценки: Up to 48 months]
• Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters [Срок оценки: Up to 48 months]
• Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters [Срок оценки: Up to 48 months]
• Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib [Срок оценки: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1]
• Arm 1: Minimum drug concentration (Cmin) [Срок оценки: Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1]
• Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (ΔQTcF) [Срок оценки: Baseline to 48 months]
• Arm 1: Change from Baseline PR interval (ΔPR) [Срок оценки: Baseline to 48 months]
• Arm 1: Change from Baseline QRS interval (ΔQRS) [Срок оценки: Baseline to 48 months]
• Arm 1: Change from baseline heart rate (ΔHR) [Срок оценки: Baseline to 48 months]
• Arm 1: Change in electrocardiogram (ECG) waveform morphology [Срок оценки: Baseline to 48 months]
• Arm 1 and Arm 2: Overall response rate [Срок оценки: Up to 48 months]
• Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants [Срок оценки: Up to 48 months]

Критерии участия

Критерии включения

• Low Grade Glioma \& Low-Grade Glioma Extension: a relapsed or progressive LGG with documented known activating BRAF alteration.
• Advanced Solid Tumor: locally advanced or metastatic solid tumor with documented known or expected to be activating RAF fusion.
• Participants must have histopathologic verification of malignancy at either original diagnosis or relapse.
• Must have received at least one line of prior systemic therapy and have documented evidence of radiographic progression.
• Must have at least 1 measurable lesion as defined by RANO (Arms 1 \& 2) or RECIST v1.1 (Arm 3) criteria

Критерии исключения

• Participant's tumor has additional previously-known activating molecular alterations.
• Participant has symptoms of without radiographically recurrent or radiographically progressive disease.
• Known or suspected diagnosis of neurofibromatosis type 1 (NF-1) via genetic testing or current diagnostic criteria.

Other inclusion/exclusion criteria as stipulated by protocol may apply

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 14 центров

• UCSF Benioff Children's Hospital — San Francisco
• Children's National Medical Center — Washington D.C.
• Lurie Children's Hospital of Chicago — Chicago
• Johns Hopkins Hospital — Baltimore
• Dana-Farber Cancer Institute — Boston
• CS Mott Children's Hospital — Ann Arbor
• St. Louis Children's Hospital — St Louis
• NYU Langone Health — New York
• … и ещё 6 центров

Австралия · 5 центров

• Queensland Children's Hospital — Brisbane
• Royal Children's Hospital — Parkville
• Perth Children's Hospital — Perth
• Sydney Children's Hospital — Randwick
• The Children's Hospital at Westmead — Westmead

Канада · 3 центра

• Centre Hospitalier Universitaire Ste-Justine — Montreal
• Montreal Children's Hospital — Montreal
• Centre Mère-Enfant Soleil du CHU — Québec

Израиль · 3 центра

• Rambam Health Care Campus — Haifa
• Schneider Children's Medical Center of Israel — Petah Tikva
• The Chaim Sheba Medical Center — Ramat Gan

Германия · 2 центра

• Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Otto-Heubner-Centrum für Kind — Berlin
• Hopp-Kindertumorzentrum Heidelberg (KiTZ), KiTZ Clinical Trial Unit (ZIPO) — Heidelberg

South Korea · 2 центра

• Seoul National University Hospital — Seoul
• Severance Hospital - Yonsei University — Seoul

Великобритания · 2 центра

• UCL Great Ormond Street Institute of Child Health — London
• Newcastle University — Newcastle upon Tyne

Дания · 1 центр

• Rigshospitalet — Copenhagen

Нидерланды · 1 центр

• Princess Maxima Center for Pediatric Oncology — Utrecht

Сингапур · 1 центр

• KK Women's and Children's Hospital — Singapore

Швейцария · 1 центр

• Universitäts-Kinderspital Zürich - Eleonorenstiftung — Zurich

Публикации

• Kilburn LB, Khuong-Quang DA, Hansford JR, Landi D, van der Lugt J, Leary SES, Driever PH, Bailey S, Perreault S, McCowage G, Waanders AJ, Ziegler DS, Witt O, Baxter PA, Kang HJ, Hassall TE, Han JW, Hargrave D, Franson AT, Yalon Oren M, Toledano H, Larouche V, Kline C, Abdelbaki MS, Jabado N, Gottardo NG, Gerber NU, Whipple NS, Segal D, Chi SN, Oren L, Tan EEK, Mueller S, Cornelio I, McLeod L, Zhao PMID 37978284

Идентификаторы

NCT: NCT04775485 · DAY101-001/PNOC026

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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