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

Study Purpose

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 patients with pediatric low-grade glioma (LGG) harboring an activating rapidly accelerated fibrosarcoma (RAF) alteration requiring front-line systemic therapy.

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	N/A - 25 Years
Gender	All

More Inclusion & Exclusion Criteria

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:

- Patient has any of the following tumor-histological findings: 1.

Schwannoma. 2. Subependymal giant cell astrocytoma (Tuberous Sclerosis) 3. Diffuse intrinsic pontine glioma, even if histologically diagnosed as World Health Organization (WHO) Grade I-II.

- Patient's tumor has additional pathogenic molecular alterations, including but not limited to a) IDH 1/2 mutation, b) Histone H3 mutation, and c) NF-1 loss of function alteration.

- Known or suspected diagnosis of neurofibromatosis Type 1 or 2 (NF-1/NF-2) - Prior or ongoing nonsurgical anticancer therapy for this indication (eg, chemotherapy, oral/intravenous targeted therapy) including radiation

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05566795
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	Day One Biopharmaceuticals, Inc.
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	N/A
Principal Investigator Affiliation	N/A
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry, Other
Overall Status	Recruiting
Countries	Australia, Austria, Belgium, Canada, Czechia, Denmark, Finland, France, Germany, Greece, Hungary, Ireland, Israel, Italy, Korea, Republic of, Netherlands, New Zealand, Norway, Singapore, Slovenia, Spain, Sweden, Switzerland, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Low-grade Glioma

Additional Details

Approximately 400 treatment-naïve low-grade glioma patients 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. Patients will continue tovorafenib until any of the following occurs: disease progression based on Response Assessment in Neuro-Oncology (RANO-LGG) criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study. Arm 2 (Investigator's Choice of SoC Chemotherapy): patients will receive one of 3 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, or vinblastine (VBL) regimen.

The choice of SoC chemotherapy regimen will be selected prior to patient randomization. Treatment will continue until completion of therapy or until any of the following occurs: disease progression based on RANO-LGG criteria, unacceptable toxicity, withdrawal of consent to treatment, or end of study. Patients who discontinue treatment due to disease progression will have

(1) radiographic evidence of progressive disease based on RANO-LGG, as determined by the Investigator and confirmed by the IRC, or (2) clinical progression based on RANO-LGG criteria determined by the Investigator.

Investigators are encouraged to discuss cases of clinical progression and early radiographic progression without clinical symptom with the Sponsor Medical Monitor prior to treatment discontinuation or initiation of a different form of treatment for the malignancy. Patients may continue therapy beyond progressive disease

Arms & Interventions

Arms

Experimental: Arm #1

Tovorafenib

Active Comparator: Arm #2

Investigator's choice of one of the following current standard of care for pediatric patients with low-grade gliomas: Children's Oncology Group - Vincristine/Carboplatin (COG-V/C) International Society for Paediatric Oncology - Low-Grade Glioma Vincristine/Carboplatin (SIOPe-LGG-V/C) Vinblastine (VBL)

Interventions

Drug: - Tovorafenib

Oral type II RAF kinase inhibitor

Drug: - Chemotherapeutic Agent

Intravenous solution for injection

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Children's of Alabama, Birmingham, Alabama

Status

Recruiting

Address

Children's of Alabama

Birmingham, Alabama, 35233

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