Patients with pediatric low-grade glioma (pLGG) who received tovorafenib (Ojemda) experienced deep and durable responses and were able to maintain disease control during extended periods off of therapy, according to updated data from the phase 2 FIREFLY-1 trial (NCT04775485) presented during the 

2025 Society for Neuro-Oncology Annual Meeting

At a median follow-up of 40.6 months, tovorafenib elicited an objective response rate of 53% by independent radiology review committee (IRC) assessment and RAPNO criteria in evaluable patients in arm 1 (n = 76); the partial response (PR) rate was 39%, the minor response (MR) rate was 13%, the stable disease rate was 29%, the progressive disease rate was 17%, and 1% of patients were not evaluable (NE) for response. The median time to response (TTR) was 5.4 months (range, 1.6-17.5), and the median duration of response (DOR) was 19.4 months (95% CI, 13.8-27.2). The median change in tumor size was –47.3% (–97.3% to –162.0).

The prespecified secondary end point of progression-free survival (PFS) was also assessed by IRC and RAPNO criteria and was reported to be a median of 16.6 months (95% CI, 8.3-19.1). The median radiographic PFS was also 16.6 months (95% CI, 10.9-22.0). Notably, the median time to next treatment, which was defined as time from the first tovorafenib dose to the start of first subsequent anticancer therapy or date of death, was 42.6 months (95% CI, 36.7-NE).

A total of 39 patients entered a treatment-free observation period, and most of them (77%) were treatment free for at least 1 year. The median treatment-free interval, which was defined as the end of primary treatment with tovorafenib to the initiation of the next subsequent anticancer therapy or death, was not reached (95% CI, NE-NE). The median duration of treatment was 24.6 months (range, 16.0-38.7), and the median follow-up from last dose to subsequent anticancer treatment was 16.0 months (range, 1.4-24.5).

Tumor rebound was reported to be minimal in the first 6 months off therapy, with 31% of patients experiencing an increase in tumor size of at least 25% from the last scan before the last dose. Additionally, early evidence of retreatment activity was observed in those who were retreated with the agent (n = 8). At the time of data cutoff, all 8 patients were still on therapy, and the median tumor size was smaller than the size recorded before retreatment was started, with a median change of –38.3%. The median duration of retreatment was 9.0 months (range, 2.6-18.0), and the median number of cycles of tovorafenib received during retreatment was 10.5.

“All of [this] is further supporting the clinical benefit of utilizing tovorafenib as an effective therapy in children and young adults with recurrent/refractory low-grade glioma,” Cassie Kline, MD, MAS, director of clinical research in the Division of Neuro-Oncology at the Children’s Hospital of Philadelphia, in Pennsylvania, said in a presentation of the data. In a news release,

 she added, “This approach has the potential to offer patients and their families meaningful time away from treatment.”

What was the design of the FIREFLY-1 trial, and what makes this research significant?

The open-label, single-arm, FIREFLY-1 trial enrolled patients with relapsed or refractory pLGG harboring an activating 

 alteration per local laboratory testing.

 To participate, patients needed to have at least 1 measurable lesion by RANO 2010 criteria, have received 1 or more prior lines of systemic therapy, and experienced radiographic progression. If patients had a known or suspected diagnosis of neurofibromatosis type 1 or had tumors harboring additional activating molecular alterations like 

Specifically, arm 1 was the registrational portion of the research, and included 77 children and young adults with recurrent or progressive pLGG and a known activating 

 Arm 2 was the pLGG extension and comprised 60 children and young adults with recurrent or progressive pLGG and a known or expected activating 

 V600 mutations. Arm C included up to 20 patients with advanced solid tumors.

Participants were given tovorafenib at an approximate dose of 420 mg/m

 once weekly in 28-day cycles according to body surface area, with doses ranging from 290 mg/m

 The primary treatment period consisted of 26 cycles of tovorafenib equating to approximately 24 months;

 treatment continued until progressive disease or intolerable toxicity.

 Subsequently, patients were able to continue treatment with tovorafenib or opt into a post-treatment observation period.

For arm 1, the primary end point was ORR by RANO-HGG criteria, and secondary end points included safety, ORR by RAPNO-LGG criteria, clinical benefit rate (CBR), TTR, DOR, and PFS based on RAPNO-LGG criteria. Exploratory end points were ORR and CBR by RANO-LGG criteria, time to next treatment, and treatment-free interval. Post-hoc analyses evaluated clinical and radiographic progression.

Earlier findings from FIREFLY-1 revealed that tovorafenib (n = 76) elicited an ORR of 51% (95% CI, 40%-63%), which comprised a PR rate of 37% and a MR rate of 14%.

 The median DOR was 13.8 months (95% CI, 11.3- NE); the 6- and 12-month DOR rates were 85% and 23%, respectively. Additionally, the median TTR was 5.3 months (range, 1.6-11.2).

 fusions or rearrangements (n = 64), the ORR achieved with tovorafenib was 52%; in those with 

V600E mutation (n = 12), this rate was 50%. Moreover, those who had prior exposure to MAPK-targeted therapy (n = 45) experienced an ORR of 49%, and those who had not previously received that kind of targeted therapy (n = 31) had a slightly higher ORR of 55%. The ORR by RANO-LGG 2011 criteria was 53% (95% CI, 41%-64%).

These data supported the FDA’s decision in April 2024 to grant 

 for pediatric patients aged 6 months and older with relapsed or refractory low-grade glioma and a 

, of the University of Washington School of Medicine, further discussed the significance of the decision in an 

 “Pediatric low-grade gliomas are the most common tumors that we see in children. They are considered benign, but we believe that word is not appropriate when something is in the brain because it’s an essential part of how we function,” she said. “Low-grade glioma can be life threatening, and there were no FDA-approved medical therapies for low-grade glioma until tovorafenib—it’s the first drug to ever apply for FDA approval for this disease.”

Sarah E. S. Leary, MD, MS, discusses the FDA approval of tovorafenib for pediatric patients with relapsed/refractory, BRAF-mutant low-grade glioma.

Dr Leary on the FDA Approval of Tovorafenib for Pediatric R/R BRAF+ Low-Grade Glioma

What was learned about the safety profile of tovorafenib?

In the safety analysis set, comprised of patients in arms 1 and 2 (n = 137), no new safety signals were observed with additional follow-up.

 Treatment-related adverse effects (TRAEs) occurred in 99% of patients, and 66% of these effects were grade 3 or higher. Moreover, TRAEs led to discontinuation for 13% of patients.

The most common grade 3 or higher TRAEs were decreased growth velocity (34%), anemia (14%), increased creatinine phosphokinase (11%), maculopapular rash (8%), and increased alanine aminotransferase level (5%).

Kline C, Hargrave D, Khong-Quang D-A, et al. Clinical stability following tovorafenib treatment in relapsed/refractory pediatric low-grade glioma: Updated results from the phase 2 FIREFLY-1 trial. Presented at: 2025 Society of Neuro-Oncology Annual Meeting; November 19-23, 2025; Honolulu, HI. Abstract CTP-17.

Day One announces three year follow-up data from Ojemda (tovorafenib) phase 2 FIREFLY-1 trial at the 2025 Society for Neuro-Oncology (SNO) Annual Meeting. News release. Day One Biopharmaceuticals, Inc. November 25, 2025. Accessed December 2, 2025. https://ir.dayonebio.com/news-releases/news-release-details/day-one-announces-three-year-follow-data-ojemdatm-tovorafenib

Ojemda. Prescribing information. Day One Biopharmaceuticals, Inc; 2024. Accessed December 2, 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217700s000lbl.pdf

FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma. FDA. April 23, 2024. Accessed December 2, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tovorafenib-patients-relapsed-or-refractory-braf-altered-pediatric

Leary SES. Dr Leary on the FDA approval of tovorafenib for pediatric R/R 

+ low-grade glioma. OncLive.com. April 23, 2024. Accessed December 2, 2025. 

https://www.onclive.com/view/dr-leary-on-the-fda-approval-of-tovorafenib-for-pediatric-r-r-braf-low-grade-glioma

Hollasch M. Tovorafenib offers an efficacious option for R/R 

-positive pediatric low-grade glioma. OncLive.com. May 28, 2024. Accessed December 2, 2025. 

https://www.onclive.com/view/tovorafenib-offers-an-efficacious-option-for-r-r-braf-positive-pediatric-low-grade-glioma

Articles

Updated data from the phase 2 FIREFLY-1 trial demonstrate that tovorafenib (Ojemda) provides significant clinical benefits for patients with pediatric low-grade glioma (pLGG), showing deep and durable responses. The trial reported a 53% objective response rate, with a median duration of response of 19.4 months. Progression-free survival was 16.6 months, and the median time to next treatment was 42.6 months. The safety profile was consistent with previous findings, with no new safety signals. Tovorafenib's efficacy led to its accelerated FDA approval for relapsed or refractory BRAF-altered pLGG.

Tovorafenib produced deep, durable responses in pLGG, with long treatment-free intervals and minimal tumor rebound after therapy.

Updated FIREFLY-1 Data Further Support Tovorafenib as a SOC in R/R Pediatric Low-Grade Glioma

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, we had the pleasure of speaking with Cassie Kline, MD, MAS, about updated efficacy data from the phase 2 FIREFLY-1 study (NCT04775485) of tovorafenib (Ojemda) in patients with relapsed/refractory pediatric low-grade glioma (pLGG) that were presented at the 2025 Society of Neuro-Oncology Annual Meeting. Dr Kline is an attending physician and director of Clinical Research in the Department of Neuro-Oncology at Children's Hospital of Philadelphia in Pennsylvania.

In our exclusive interview, Dr Kline discussed longer-term efficacy and safety data from the trial, noting the sustained response rates, continued tumor shrinkage, and rates of patients who remained treatment free after approximately 36 months of follow-up.

That’s all we have for today! Thank you for listening to this episode of 

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Podcasts

Dr Kline discusses longer-term efficacy data from the FIREFLY-1 study of tovorafenib in patients with relapsed/refractory pediatric low-grade glioma.

Tovorafenib Yields Long-Term Efficacy in Pediatric Low-Grade Glioma: With Cassie Kline, MD, MAS

Dr Kline on Updated Efficacy Data With Tovorafenib in R/R Pediatric Low Grade Glioma

"The time to next treatment being over 40 months for our patient population, ideally, is giving our patients and families this nice long period of not necessarily needing additional therapies."

Cassie Kline, MD, MAS, an attending physician and director of clinical research in the Department of Neuro-Oncology at the Children's Hospital of Philadelphia, shared updated results from the ongoing phase 2 FIREFLY-1 study (NCT04775485) evaluating tovorafenib (Ojemda) in relapsed/refractory pediatric low-grade glioma (pLGG).

supported the FDA approval of tovorafenib

-altered pLGG in April 2024. The updated data, encompassing approximately 36 months of follow-up, were presented at the 

The results demonstrated that tovorafenib induced durable responses in patients with recurrent 

-altered pLGG. Updated data showed that evaluable patients (n = 76) achieved an overall response rate (ORR) of 53%, including a partial response rate of 39% and a minor response rate of 13%. The median duration of response was 19.4 months (95% CI, 13.8-27.2), and the median time to response was 5.4 months (95% CI, 1.6-17.5). Kline highlighted that the updated data identified a very long period of time to next treatment, which was 42.6 months (95% CI, 36.7-not evaluable). 

However, the study also confirmed favorable treatment completion and treatment-free intervals, she said. The majority of patients (58%) were able to finish at least 26 cycles of therapy, and most who stopped treatment after completing 26 cycles were able to remain treatment-free for up to a year. This long interval could offer patients and families a significant period without needing additional therapies, Kline noted.

These findings are promising regarding the agent's potential clinical benefit, tolerability, and ongoing disease control once patients cease treatment, Kline stated. Furthermore, the updated follow-up identified no new safety signals, she added. The cohort now includes a small number of patients who have entered a retreatment arm after coming off the drug and experiencing tumor changes that warranted a second course of therapy. Kline expressed excitement over seeing the response data from the 3-year follow-up and the retreatment cohort.

Videos

Cassie Kline, MD, MAS, discusses 3-year follow-up data with tovorafenib in patients with pediatric low-grade glioma from FIREFLY-1. 



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Updated FIREFLY-1 Data Further Support Tovorafenib as a SOC in R/R Pediatric Low-Grade Glioma

Tovorafenib Yields Long-Term Efficacy in Pediatric Low-Grade Glioma: With Cassie Kline, MD, MAS

Dr Kline on Updated Efficacy Data With Tovorafenib in R/R Pediatric Low Grade Glioma