News|Articles|December 1, 2025
Tovorafenib Yields Durable, Long-Term Disease Control in R/R Low-Grade Glioma
Author(s)Paige Britt
Fact checked by: Andrea Eleazar, MHS
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Key Takeaways
- Tovorafenib provides durable disease control in pediatric patients with relapsed or refractory low-grade glioma harboring BRAF alterations.
- A significant majority of patients remained off subsequent anticancer treatment for at least 12 months post-therapy.
Tovorafenib shows promising long-term efficacy for pediatric low-grade glioma, with significant treatment-free intervals and manageable safety profile.
Three-year follow-up data from the phase 2 FIREFLY-1 (NCT04775485) trial show that tovorafenib (Ojema) provides durable, long-term disease control for pediatric patients with relapsed or refractory (R/R) low-grade glioma (pLGG) harboring a BRAF alteration.1,2
Data were presented at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting.
A significant majority (77%) of patients who entered a treatment-free observation period after completing therapy remained off any subsequent anticancer treatment for at least 12 months, highlighting the durability of the response.
The median time to next treatment following initiation of tovorafenib was 42.6 months (over 3.5 years), indicating a substantial delay in the need for subsequent therapies.
For patients whose disease progressed after stopping treatment, re-initiating tovorafenib proved effective (n = 8), achieving a median maximum tumor reduction of -38.3%.
The overall response rate was 53% (n = 40/76). The duration of response was 19.4 months (95% CI, 13.8–27.2). The median time to response was 5.4 months (95% CI, 1.6–17.5). The median progression-free survival was 16.6 months (95% CI, 10.9–22.0).
Safety Profile
The extended follow-up identified no new safety signals, reinforcing the established tolerability of the treatment.
The most common grade ≥3 adverse events, which occurred in ≥ 5% of patients, were decreased growth velocity, anemia, blood creatine phosphokinase elevation, maculopapular rash, and alanine aminotransferase elevation.
The most common adverse reactions, which occurred in ≥30% of patients, were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection.
The
About the FIREFLY-1 Trial
The objective of the study is to evaluate the safety and efficacy of tovorafenib as a once-weekly monotherapy in patients aged 6 months to 25 years with relapsed or progressive pLGG harboring a known activating BRAF alteration. Tovorafenib is a type 2 RAF kinase inhibitor designed to target mutant BRAF V600, wild-type BRAF, and wild-type CRAF kinases.
The pivotal study consisted of 2 arms. Arm 1 (n = 77) was used for efficacy analyses, while arm 2 (n = 60) was initiated to provide additional safety data and enable patient access.
The 3-year follow-up data is based on a data cutoff date of June 6, 2025, with a median study duration of 40.6 months for the 76 evaluable patients in arm 1.
“We are excited by these updated 3-year data showing that patients taking tovorafenib were able to spend meaningful time off therapy, with the option to retreat as needed,” said Elly Barry, MD, chief medical officer of Day One, in a news release.1 “These findings highlight the potential for a treatment approach to help support patients through the long-term course of their disease and further support our view that tovorafenib has the potential to become the second line standard of care in pLGG.”
Tovorafenib is currently being evaluated as a front-line therapy for patients aged 6 months to 25 years with pLGG in the phase 3 FIREFLY-2/LOGGIC trial (NCT05566795).3
REFERENCES
1.Day One announces three year follow-up data from the OJEMDA™ (tovorafenib) phase 2 FIREFLY-1 trial at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting. News release. Day One. Published November 24, 2025. Accessed November 26, 2025. https://tinyurl.com/bdek4dzh
2.A study to evaluate tovorafenib in pediatric and young adult participants with relapsed or progressive low-grade glioma and advance solid tumors (FIREFLY-1). ClincalTrials.gov. Updated April 10, 2025. Accessed November 26, 2025. https://clinicaltrials.gov/study/NCT04775485
3.DAY101 vs. standard of care chemotherapy in pediatric participants with low-grade glioma requiring first-line systemic therapy (LOGGIC/FIREFLY-2). ClinicalTrials.gov. Updated November 6, 2025. Accessed November 26, 2025. https://clinicaltrials.gov/study/NCT05566795
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