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NCT Number: NCT05566795

DAY101 vs. Standard of Care Chemotherapy in Pediatric Participants With Low-Grade Glioma Requiring First-Line Systemic Therapy (LOGGIC/FIREFLY-2)

This is a 2-arm, randomized, open-label, multicenter, global, Phase 3 trial to evaluate the efficacy, safety, and tolerability of tovorafenib monotherapy versus standard of care (SoC) chemotherapy in participants with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring first-line systemic therapy.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Low-grade Glioma Noonan Syndrome 5 Pediatric Low-grade Glioma Rapidly Accelerated Fibrosarcoma (RAF) Altered Glioma

Age range

Up to 25 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Children's Health Queensland Hospital and Health Service, South Brisbane, Queensland, Australia

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About this study

Approximately 400 treatment-naïve LGG participants will be randomized 1:1 to either tovorafenib (Arm 1) or an Investigator's choice of SoC chemotherapy (Arm 2).

Arm 1 (tovorafenib): Treatment cycles will repeat every 28 days in the absence of disease progression. Participants will continue tovorafenib until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Arm 2 (Investigator's Choice of SoC Chemotherapy): Participants will receive one of 4 SoC chemotherapy options selected by the treating Investigator: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) regimen, International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) regimen, vinblastine (VBL) regimen, or monthly carboplatin. The choice of SoC chemotherapy regimen will be selected prior to participant randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression, unacceptable toxicity, withdrawal of consent to treatment, or end of study.

Participants who discontinue treatment due to disease progression will have (1) radiographic evidence of disease progression, as determined by the Investigator, or (2) clinical progression, as determined by the Investigator. Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptoms with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Participants may continue therapy beyond progressive disease (PD).

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Less than 25 years of age with LGG with known activating RAF alteration.
  • Histopathologic diagnosis of glioma or glioneuronal tumor.
  • At least one measurable lesion as defined by RANO criteria.
  • Meet indication for first-line systemic therapy.

Exclusion criteria

  • Participant has any of the following tumor-histological findings:
  • Schwannoma
  • Subependymal giant cell astrocytoma (Tuberous Sclerosis)
  • Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II
  • Participant's tumor has additional pathogenic molecular alterations, including but not limited to a) isocitrate dehydrogenase (IDH) 1/2 mutation, b) Histone H3 mutation, and c) neurofibromatosis Type 1 (NF-1) loss of function alteration.
  • Known or suspected diagnosis of NF-1/ neurofibromatosis Type 2 (NF-2).
  • Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/IV targeted therapy) including radiation.

Treatment and study plan

Tovorafenib

Drug

Oral Tablet Powder for Oral Suspension

Other names: DAY101, Ojemda

Chemotherapeutic Agent

Drug

Intravenous solution for injection

Other names: COG-V/C, SIOPe-LGG-V/C, VBL, Carboplatin

Primary outcomes

  1. Objective response rate (ORR) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    ORR assessed per Response Assessment in Pediatric Neuro Oncology (RAPNO) criteria by Independent Review Committee (IRC), and defined as the proportion of participants with overall confirmed response of complete response (CR), partial response (PR), or minor response (MR).

Secondary outcomes

  1. Progression-free survival (PFS) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    PFS assessed per RAPNO criteria by IRC, and defined as time from randomization to PD or death from any cause, whichever comes first.

  2. Event-free survival (EFS) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    EFS assessed per RAPNO criteria by IRC, defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.

  3. Overall survival (OS) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    Overall survival is defined as time from randomization up to death from any cause.

  4. Number of participants with any treatment-emergent adverse events, and Serious adverse events

    Time frame: Up to 60 months

    Type, frequency, and severity of adverse events of tovorafenib monotherapy versus SoC chemotherapy will be assessed.

  5. . Number of participants with clinically significant vital signs and laboratory abnormalities findings

    Time frame: Up to 60 months

    Type, frequency, and severity of vital signs and laboratory abnormalities of tovorafenib monotherapy versus SoC chemotherapy will be assessed.

  6. Change from baseline in Adaptive Behavior Composite Score (ABS) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    Adaptive behavior Composite Score will be evaluated using domain scores collected from the comprehensive Vineland III Adaptive Behavior Scale (VABS).

  7. Change from baseline in the Motor Skills Domain Score of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    The motor skills (gross and fine) will be assessed using the Motor Skills Score domain of the VABS in pediatric participants.

  8. Change from baseline in the Daily Living Domain Score of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    The daily living (personal, domestic and community) will be assessed using Daily Living Domain Score of VABS.

  9. Change from baseline in the Communication Domain Score of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    The communication skills (receptive, expressive and written) will be assessed using Communication Domain Score of VABS.

  10. Change from baseline in the Socialization Domain Score of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    The socialization skills (Interpersonal relationships, play and leisure time and coping skills) will be assessed using Socialization Domain Score of VABS.

  11. Change in age-adjusted visual acuity (VA) of tovorafenib monotherapy versus SoC chemotherapy in optic pathway glioma (OPG) participants aged < 3 years

    Time frame: Baseline and up to 5 years

    Visual acuity testing using current age-appropriate testing methodology will be performed for all participants at Screening. For participants with OPG or an underlying visual deficit related to the primary malignancy, visual acuity testing will be performed every time participants have a radiographic response assessment. Assessments will be performed in each eye separately at a recommended testing distance of 3 meters.

  12. Change in best corrected visual acuity of tovorafenib monotherapy versus SoC chemotherapy in OPG participants aged ≥ 3 years

    Time frame: Baseline and up to 5 years

    Visual acuity assessments to be performed by an ophthalmologist or another qualified site clinical personnel.

  13. Visual progression-free survival (v-PFS) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    Visual progression-free survival is defined as the time from start of treatment to visual event for OPG participants aged ≥ 3 years.

  14. ORR of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    ORR, defined as the proportion of participants with overall confirmed response per Response Assessment in Neuro-Oncology for High-Grade Glioma (RANO-HGG) criteria (CR or PR) and RANO-LGG criteria (CR, PR, or MR), as applicable.

  15. Clinical benefit rate (CBR) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    CBR, defined as the proportion of participants with radiological tumor stabilization or regression per RANO-LGG (CR, PR, MR, or SD lasting 12 months or more), RANO-HGG (CR, PR, or SD lasting 12 months or more) or RAPNO criteria (CR, PR, MR or SD lasting 12 months or more), as applicable.

  16. Time to response (TTR) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    TTR, measured by the time following randomization to first imaging of tumor response that was subsequently confirmed per RANO-HGG criteria (CR or PR), RANO-LGG criteria (CR, or PR, or MR), or RAPNO criteria (CR, PR, or MR), as applicable.

  17. PFS of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    PFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD or death from any cause, whichever occurs first.

  18. EFS of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    EFS per RANO-HGG or RANO-LGG criteria (as applicable), defined as time from randomization to PD, death from any cause, or initiation of any new anticancer therapy, whichever comes first.

  19. Duration of response (DOR) of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Up to 60 months

    DOR, defined as time from first imaging of tumor response per RANO-LGG, RANO-HGG or RAPNO criteria, as applicable, that was subsequently confirmed to radiographic PD or death from any cause, whichever comes first.

  20. Change from Baseline in health-related quality of life (HRQoL) total score of tovorafenib monotherapy versus SoC chemotherapy

    Time frame: Baseline, Year 1, 2 and 5

    The Patient-Reported Outcomes Measurement Information System (PROMIS®) Pediatric/Parent Proxy Profile 49 v2.0 will be used to assess mental and social HRQoL.

Sponsors and collaborators

Lead sponsor

Day One Biopharmaceuticals, Inc.

Industry

Collaborators

  • SIOPe Brain Tumor Group LOGGIC Consortium

Registry information

Official study title

LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial of DAY101 Monotherapy Versus Standard of Care Chemotherapy in Patients With Pediatric Low-Grade Glioma Harboring an Activating RAF Alteration Requiring First-Line Systemic Therapy

Important dates

Study start
2023
Primary completion
2027
Study completion
2031
First posted
Oct 4, 2022
Registry last updated
May 14, 2026

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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