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NCT Number: NCT04775485

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

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.

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Key information

Conditions

Low-grade Glioma Advanced Solid Tumor

Age range

6 month–25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Queensland Children's Hospital, Brisbane, Australia

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Other inclusion/exclusion criteria as stipulated by protocol may apply

Treatment and study plan

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.

Other names: DAY101

Primary outcomes

  1. Arm 1: Overall response rate

    Time frame: Up to 48 months

    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.

  2. Arm 2: Number of participants reporting adverse events

    Time frame: Up to 48 months

    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.

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

    Time frame: Up to 48 months

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

    Time frame: Up to 48 months

  5. Arm 3: Overall response rate

    Time frame: Up to 48 months

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

Secondary outcomes

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

    Time frame: Up to 48 months

    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.

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

    Time frame: Up to 48 months

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

    Time frame: Up to 48 months

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

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

  5. Arm 1: Minimum drug concentration (Cmin)

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

  6. Arm 1: Change from Baseline QT interval corrected for heart rate by Fridericia's formula (ΔQTcF)

    Time frame: Baseline to 48 months

  7. Arm 1: Change from Baseline PR interval (ΔPR)

    Time frame: Baseline to 48 months

  8. Arm 1: Change from Baseline QRS interval (ΔQRS)

    Time frame: Baseline to 48 months

  9. Arm 1: Change from baseline heart rate (ΔHR)

    Time frame: Baseline to 48 months

  10. Arm 1: Change in electrocardiogram (ECG) waveform morphology

    Time frame: Baseline to 48 months

  11. Arm 1 and Arm 2: Overall response rate

    Time frame: Up to 48 months

    ORR is defined as percentage of participants with best overall confirmed response of CR or PR by the RANO-HGG criteria.

  12. Arm 1, Arm 2 and Arm 3: Overall response rate in Pediatric participants

    Time frame: Up to 48 months

    ORR is defined as percentage of participants with best overall confirmed response of CR or PR or minor response (MR) by Response Assessment in Pediatric Neuro-Oncology (RAPNO) criteria.CR or PR by RECIST v1.1 criteria.

  13. Arm 1, Arm 2 and Arm 3: duration of progression-free survival (PFS)

    Time frame: Up to 48 months

    PFS as defined by the time following initiation of tovorafenib to progression or death in participants treated with tovorafenib measured by RECIST v1.1, RAPNO, or RANO-HGG criteria as determined by the treating investigator and an IRC.

  14. Arm 1, Arm 2 and Arm 3: Duration of response (DOR)

    Time frame: Up to 48 months

    DOR as defined by the length of response in participants with best overall confirmed response of CR or PR or MR and measured by RANO-HGG, RAPNO, and/or RECIST v1.1 criteria, as applicable.

  15. Arm 1, Arm 2 and Arm 3: Time to response (TTR)

    Time frame: Up to 48 months

    TTR as defined as the time to first response following initiation of tovorafenib in participants with best overall confirmed response of CR or PR measured by RECIST v1.1 or RANO-HGG criteria, as applicable.

  16. Arm 1, Arm 2 and Arm 3: Clinical benefit rate (CBR)

    Time frame: Up to 48 months

    CBR as defined as participants with BOR of CR, PR or stable disease (SD) measured by RECIST v1.1 or RANO-HGG, as applicable, and lasting 12 months or more following initiation of tovorafenib.

  17. Arm 1 and Arm 2: Duration of overall survival

    Time frame: Up to 48 months

    Overall survival as defined by the time following initiation of tovorafenib to death of any cause in participants treated with tovorafenib.

  18. Arm 1: Change from baseline in best corrected visual acuity (BCVA) outcomes

    Time frame: Baseline to 48 months

  19. Arm 1: Changes in molecular analysis of cells obtained from archival tissue

    Time frame: At Screening

Study contacts

Contact information is provided by the study sponsor or research team.

Day One Biopharmaceuticals, Inc.

CONTACT

[email protected]

650-484-0899

Sponsors and collaborators

Lead sponsor

Day One Biopharmaceuticals, Inc.

Industry

Collaborators

  • Pacific Pediatric Neuro-Oncology Consortium

Registry information

Official study title

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

Acronym: FIREFLY-1

Important dates

Study start
2021
Primary completion
2027
Study completion
2027
First posted
Mar 1, 2021
Registry last updated
Apr 10, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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