141 Participants Needed

DAY101 for Brain Tumor

(FIREFLY-1 Trial)

Recruiting at 37 trial locations
DO
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Overseen ByDay One Biopharmaceuticals, Inc.
Age: < 65
Sex: Any
Trial Phase: Phase 2
Sponsor: Day One Biopharmaceuticals, Inc.
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial
Approved in 1 JurisdictionThis treatment is already approved in other countries

Trial Summary

What is the purpose of this trial?

This trial is testing a new pill called DAY101 in young patients with certain brain tumors or advanced cancers. The pill works by blocking proteins that help cancer cells grow. The goal is to see if this treatment can control the disease in patients who have specific genetic changes.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the drug DAY101 (Tovorafenib) for brain tumors?

Research shows that Tovorafenib, a part of the DAY101 treatment, has been effective in treating pediatric low-grade glioma with BRAF alterations, achieving a 67% response rate in a clinical trial. This suggests it could be a promising option for brain tumors with similar genetic changes.12345

What safety data exists for the treatment Tovorafenib (DAY101) in humans?

In the FIREFLY-1 trial for pediatric low-grade glioma, Tovorafenib (DAY101) was generally safe but had some side effects. Common side effects included changes in hair color, increased levels of a muscle enzyme, and anemia (low red blood cell count). More severe side effects occurred in 42% of patients, and 7% of patients stopped treatment due to these effects.23678

What makes the drug DAY101 (Tovorafenib) unique for treating brain tumors?

DAY101 (Tovorafenib) is unique because it is an oral drug specifically targeting BRAF alterations, which are common in pediatric low-grade gliomas. Unlike standard chemotherapy, it is a selective type II RAF inhibitor that penetrates the central nervous system, offering a targeted approach for tumors with BRAF mutations.1291011

Eligibility Criteria

This trial is for young patients aged 6 months to 25 years with relapsed or progressive low-grade glioma (LGG) or advanced solid tumors that have a specific BRAF gene change. Participants must have at least one measurable tumor and, for certain arms of the study, must have tried at least one other treatment before joining.

Inclusion Criteria

My cancer is advanced or has spread, and tests show a RAF fusion.
I am between 6 months and 25 years old.
My low-grade glioma has returned or worsened with a known BRAF mutation.
See 3 more

Exclusion Criteria

There may be additional criteria for participation in the study as specified in the protocol.
I feel my cancer is getting worse even though scans don't show it.
I have been diagnosed with or suspected to have neurofibromatosis type 1.
See 1 more

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive tovorafenib weekly according to dose rounding guidelines and their baseline body surface area

48 months

End of Treatment (EOT) Visit

Participants undergo assessments to evaluate the end of treatment outcomes

Safety Follow-up

Participants are monitored for safety after the end of treatment

4 weeks

Long-term Follow-up

Participants are monitored for long-term safety and efficacy outcomes

48 months

Treatment Details

Interventions

  • DAY101
Trial OverviewThe FIREFLY-1 study is testing DAY101, an oral medication designed to inhibit a protein called pan-RAF which may be involved in tumor growth. The goal is to see if it's safe and effective in children and young adults with brain tumors or other solid tumors with BRAF alterations.
Participant Groups
3Treatment groups
Experimental Treatment
Group I: Arm 3: Advanced Solid TumorExperimental Treatment1 Intervention
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 II: Arm 2: Low-Grade Glioma Expanded AccessExperimental Treatment1 Intervention
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 III: Arm 1: Low-Grade GliomaExperimental Treatment1 Intervention
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).

DAY101 is already approved in United States for the following indications:

🇺🇸
Approved in United States as Ojemda for:
  • Pediatric low-grade glioma with BRAF gene mutations

Find a Clinic Near You

Who Is Running the Clinical Trial?

Day One Biopharmaceuticals, Inc.

Lead Sponsor

Trials
8
Recruited
1,100+

Pacific Pediatric Neuro-Oncology Consortium

Collaborator

Trials
16
Recruited
840+

Findings from Research

In a phase 2 trial involving 110 pediatric patients with low-grade glioma and BRAF V600 mutations, the combination of dabrafenib and trametinib resulted in a significantly higher overall response rate (47%) compared to standard chemotherapy (11%).
Dabrafenib plus trametinib also demonstrated a longer median progression-free survival (20.1 months) and a better safety profile, with fewer severe adverse events (47% vs. 94% for chemotherapy), making it a promising first-line treatment option.
Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations.Bouffet, E., Hansford, JR., Garrè, ML., et al.[2023]
In the phase 2 FIREFLY-1 trial, tovorafenib demonstrated a high overall response rate of 67% in treating pediatric low-grade glioma (pLGG) with BRAF alterations, with a median duration of response of 16.6 months.
While tovorafenib shows promise as an effective therapy, it is associated with notable treatment-related adverse events, including hair color changes (76%) and elevated creatine phosphokinase (56%), with 42% of patients experiencing grade ≥3 adverse events.
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial.Kilburn, LB., Khuong-Quang, DA., Hansford, JR., et al.[2023]
In a phase I/II study involving 139 pediatric patients with relapsed/refractory malignancies, trametinib was found to have a recommended dose of 0.032 mg/kg for children under 6 years and 0.025 mg/kg for those 6 years and older, with manageable safety profiles and no dose-limiting toxicities when combined with dabrafenib.
Among 49 patients with BRAF V600-mutant low-grade gliomas, the combination therapy of dabrafenib and trametinib showed a higher objective response rate of 25% compared to 15% for trametinib alone, indicating improved efficacy with the combination treatment.
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma.Bouffet, E., Geoerger, B., Moertel, C., et al.[2023]

References

Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. [2023]
The type II RAF inhibitor tovorafenib in relapsed/refractory pediatric low-grade glioma: the phase 2 FIREFLY-1 trial. [2023]
Efficacy and Safety of Trametinib Monotherapy or in Combination With Dabrafenib in Pediatric BRAF V600-Mutant Low-Grade Glioma. [2023]
Efficacy and Safety of Dabrafenib in Pediatric Patients with BRAF V600 Mutation-Positive Relapsed or Refractory Low-Grade Glioma: Results from a Phase I/IIa Study. [2023]
Response to the BRAF/MEK inhibitors dabrafenib/trametinib in an adolescent with a BRAF V600E mutated anaplastic ganglioglioma intolerant to vemurafenib. [2021]
Effect of early adverse events on response and survival outcomes of advanced melanoma patients treated with vemurafenib or vemurafenib plus cobimetinib: A pooled analysis of clinical trial data. [2020]
Dabrafenib plus trametinib in BRAFV600E-mutated rare cancers: the phase 2 ROAR trial. [2023]
FDA Approval Summary: Dabrafenib in combination with trametinib for BRAF V600E mutation-positive low-grade glioma. [2023]
Phase I Clinical Trial of the Wee1 Inhibitor Adavosertib (AZD1775) with Irinotecan in Children with Relapsed Solid Tumors: A COG Phase I Consortium Report (ADVL1312). [2021]
10.United Statespubmed.ncbi.nlm.nih.gov
Management of Inoperable Supra-Sellar Low-Grade Glioma With BRAF Mutation in Young Children. [2023]
Topoisomerase I inhibitors for the treatment of brain tumors. [2018]