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

NCT ID: NCT04775485

Last Updated: 2025-04-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

141 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-22

Study Completion Date

2027-05-31

Brief Summary

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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.

Detailed Description

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Conditions

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Low-grade Glioma Advanced Solid Tumor

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 1: Low-Grade Glioma

Participants with recurrent or progressive low-grade glioma will receive 420 milligrams/meters square (mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline body surface area (BSA).

Group Type EXPERIMENTAL

Tovorafenib

Intervention Type DRUG

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

Arm 2: Low-Grade Glioma Expanded Access

Participants with recurrent or progressive low-grade glioma will receive 420 mg/m\^2 of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.

Group Type EXPERIMENTAL

Tovorafenib

Intervention Type DRUG

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

Arm 3: Advanced Solid Tumor

Participants with advanced solid tumors will receive 420 mg/m\^2) of tovorafenib weekly according to dose rounding guidelines and according to their baseline BSA.

Group Type EXPERIMENTAL

Tovorafenib

Intervention Type DRUG

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

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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DAY101

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

25 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Pacific Pediatric Neuro-Oncology Consortium

OTHER

Sponsor Role collaborator

Day One Biopharmaceuticals, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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UCSF Benioff Children's Hospital

San Francisco, California, United States

Site Status RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Lurie Children's Hospital of Chicago

Chicago, Illinois, United States

Site Status RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, United States

Site Status TERMINATED

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

CS Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status RECRUITING

NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Duke Cancer Center

Durham, North Carolina, United States

Site Status RECRUITING

Doernbecher Children's Hospital Oregon & Health Science University

Portland, Oregon, United States

Site Status TERMINATED

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status RECRUITING

Texas Children's Hospital

Houston, Texas, United States

Site Status RECRUITING

University of Utah

Salt Lake City, Utah, United States

Site Status RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status RECRUITING

Queensland Children's Hospital

Brisbane, , Australia

Site Status RECRUITING

Royal Children's Hospital

Parkville, , Australia

Site Status RECRUITING

Perth Children's Hospital

Perth, , Australia

Site Status RECRUITING

Sydney Children's Hospital

Randwick, , Australia

Site Status RECRUITING

The Children's Hospital at Westmead

Westmead, , Australia

Site Status RECRUITING

Centre Hospitalier Universitaire Ste-Justine

Montreal, Quebec, Canada

Site Status RECRUITING

Montreal Children's Hospital

Montreal, Quebec, Canada

Site Status RECRUITING

Centre Mère-Enfant Soleil du CHU

Québec, Quebec, Canada

Site Status RECRUITING

Rigshospitalet

Copenhagen, , Denmark

Site Status RECRUITING

Charité Universitätsmedizin Berlin, Campus Virchow Klinikum, Otto-Heubner-Centrum für Kinder

Berlin, , Germany

Site Status RECRUITING

Hopp-Kindertumorzentrum Heidelberg (KiTZ), KiTZ Clinical Trial Unit (ZIPO)

Heidelberg, , Germany

Site Status RECRUITING

Rambam Health Care Campus

Haifa, , Israel

Site Status RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, , Israel

Site Status RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, , Israel

Site Status RECRUITING

Princess Maxima Center for Pediatric Oncology

Utrecht, , Netherlands

Site Status RECRUITING

KK Women's and Children's Hospital

Singapore, , Singapore

Site Status RECRUITING

Seoul National University Hospital

Seoul, , South Korea

Site Status RECRUITING

Severance Hospital - Yonsei University

Seoul, , South Korea

Site Status RECRUITING

Universitäts-Kinderspital Zürich - Eleonorenstiftung

Zurich, , Switzerland

Site Status RECRUITING

UCL Great Ormond Street Institute of Child Health

London, , United Kingdom

Site Status RECRUITING

Newcastle University

Newcastle upon Tyne, , United Kingdom

Site Status RECRUITING

Countries

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United States Australia Canada Denmark Germany Israel Netherlands Singapore South Korea Switzerland United Kingdom

Central Contacts

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Day One Biopharmaceuticals, Inc.

Role: CONTACT

650-484-0899

Facility Contacts

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[email protected]

Role: primary

202-476-5000

References

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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 X, Walter A, Da Costa D, Manley P, Blackman SC, Packer RJ, Nysom K. The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. Nat Med. 2024 Jan;30(1):207-217. doi: 10.1038/s41591-023-02668-y. Epub 2023 Nov 17.

Reference Type DERIVED
PMID: 37978284 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

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DAY101-001/PNOC026

Identifier Type: -

Identifier Source: org_study_id

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