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

NCT04775485 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: DAY101-001/PNOC026
• Study Type: interventional
• Target: 141
• Locations: 11 countries
• Sites: 35

Brief Summary

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.

Conditions

Low-grade Glioma; Advanced Solid Tumor

Keywords

Low-grade Glioma; Advanced Solid Tumor; FIREFLY-1; DAY101; Tovorafenib

Outcome Measures

Primary Outcomes (5)

• Arm 1: Overall response rate

  ORR is defined as percentage of participants with best overall confirmed response of complete response (CR) or partial response (PR) by the Response Assessment in Neuro-Oncology - high-grade glioma (RANO-HGG) criteria.

  Up to 48 months

• Arm 2: Number of participants reporting adverse events

  An adverse event (AE) is any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention.

  Up to 48 months

• Arm 2: Number of participants with clinically significant changes in clinical chemistry parameters

  Up to 48 months

• Arm 2: Number of participants with clinically significant changes in hematology parameters

  Up to 48 months

• Arm 3: Overall response rate

  Determined by the treating investigator and measured by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 or RANO-HGG criteria, as appropriate.

  Up to 48 months

Secondary Outcomes (19)

• Arm 1 and 3: Number of participants reporting adverse events

  Up to 48 months

• Arm 1 and 3: Number of participants with clinically significant changes in clinical chemistry parameters

  Up to 48 months

• Arm 1 and 3: Number of participants with clinically significant changes in hematology parameters

  Up to 48 months

• Arm 1: Area under the concentration-time curve (AUC) of Tovorafenib

  Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1

• Arm 1: Minimum drug concentration (Cmin)

  Cycle 1: Day 1 and Day 15; Cycles 2, 4, 7, 10 and 13: Day 1

Study Arms (3)

Arm 1: Low-Grade Glioma

EXPERIMENTAL

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).

Drug: Tovorafenib

Arm 2: Low-Grade Glioma Expanded Access

EXPERIMENTAL

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.

Drug: Tovorafenib

Arm 3: Advanced Solid Tumor

EXPERIMENTAL

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.

Drug: Tovorafenib

Interventions

Tovorafenib 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.

Also known as: DAY101

Arm 1: Low-Grade Glioma; Arm 2: Low-Grade Glioma Expanded Access; Arm 3: Advanced Solid Tumor

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Day One Biopharmaceuticals, Inc.: lead
• Pacific Pediatric Neuro-Oncology Consortium: collaborator

Study Sites (35)

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

RECRUITING

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Lurie Children's Hospital of Chicago

Chicago, Illinois, 60611, United States

RECRUITING

Johns Hopkins Hospital

Baltimore, Maryland, 21231, United States

TERMINATED

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

RECRUITING

CS Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

RECRUITING

St. Louis Children's Hospital

St Louis, Missouri, 63110, United States

RECRUITING

NYU Langone Health

New York, New York, 10016, United States

RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Doernbecher Children's Hospital Oregon & Health Science University

Portland, Oregon, 97239, United States

TERMINATED

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Texas Children's Hospital

Houston, Texas, 77030, United States

RECRUITING

University of Utah

Salt Lake City, Utah, 84113, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

RECRUITING

Queensland Children's Hospital

Brisbane, 4101, Australia

RECRUITING

Royal Children's Hospital

Parkville, 3052, Australia

RECRUITING

Perth Children's Hospital

Perth, WA 6009, Australia

RECRUITING

Sydney Children's Hospital

Randwick, NSW 2031, Australia

RECRUITING

The Children's Hospital at Westmead

Westmead, 2145, Australia

RECRUITING

Centre Hospitalier Universitaire Ste-Justine

Montreal, Quebec, H3T 1C5, Canada

RECRUITING

Montreal Children's Hospital

Montreal, Quebec, H4A 3J1, Canada

RECRUITING

Centre Mère-Enfant Soleil du CHU

Québec, Quebec, G1V 4G2, Canada

RECRUITING

Rigshospitalet

Copenhagen, Denmark

RECRUITING

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

Berlin, 13353, Germany

RECRUITING

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

Heidelberg, 69120, Germany

RECRUITING

Rambam Health Care Campus

Haifa, 3109601, Israel

RECRUITING

Schneider Children's Medical Center of Israel

Petah Tikva, 4920235, Israel

RECRUITING

The Chaim Sheba Medical Center

Ramat Gan, 5265601, Israel

RECRUITING

Princess Maxima Center for Pediatric Oncology

Utrecht, 3584 CS, Netherlands

RECRUITING

KK Women's and Children's Hospital

Singapore, 229899, Singapore

RECRUITING

Seoul National University Hospital

Seoul, 3080, South Korea

RECRUITING

Severance Hospital - Yonsei University

Seoul, 3722, South Korea

RECRUITING

Universitäts-Kinderspital Zürich - Eleonorenstiftung

Zurich, 8032, Switzerland

RECRUITING

UCL Great Ormond Street Institute of Child Health

London, WC1N 1EH, United Kingdom

RECRUITING

Newcastle University

Newcastle upon Tyne, NE1 7RU, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 37978284 DERIVED

MeSH Terms

Interventions

tovorafenib

Central Study Contacts

Day One Biopharmaceuticals, Inc.

CONTACT

650-484-0899; firefly-1@dayonebio.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: March 1, 2021
• Study Start: April 22, 2021
• Primary Completion (Estimated): May 31, 2027
• Study Completion (Estimated): May 31, 2027
• Last Updated: April 10, 2025

Record last verified: 2025-03

Locations

US (14); AU (5); CA (3); SG (1); KR (2); DE (2); IL (3); NL (1); CH (1); GB (2); DK (1)