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Tovorafenib (Ojemda) has further solidified its place in the treatment landscape of relapsed/refractory pediatric low-grade glioma (pLGG) following updated data from the phase 2 FIREFLY-1 trial (NCT04775485), according to Cassie Kline, MD, MAS.

Findings from the updated 3-year analysis of FIREFLY-1 presented during the 2025 Society of Neuro-Oncology Annual Meeting demonstrated that efficacy-evaluable patients with relapsed/refractory pLGG who received tovorafenib in arm 1 (n = 76) achieved an overall response rate (ORR) of 53%.¹ The median duration of response (DOR) was 19.4 months (95% CI, 13.8-27.2) and the median time to response was 5.4 months (range, 1.6-17.5). The median time to next treatment (TTNT) was 42.6 months (95% CI, 36.7-not estimable).

“We were able to identify a very long period of TTNT [with] additional follow-up, [with] no new safety signals,” Kline said in an interview in OncLive®. “We now have a cohort, although [it’s] still small numbers, that have also entered a retreatment arm after coming off of the drug and seeing tumor changes that warranted retreatment. We were excited to see the response of the 3-year follow up data that are adding on to what was previously presented and published.”

In the interview, Kline, an attending physician and director of clinical research in the Department of Neuro-Oncology at Children’s Hospital of Philadelphia in Pennsylvania, discussed the design of FIREFLY-1, the mechanism of action of tovorafenib, and the significance of the key findings from the study.

OncLive: What was the rationale and study design characteristics of FIREFLY-1?

Kline: The trial was designed for [patients with] recurrent pLGG. There’s also a solid tumor cohort. As a pediatric-neuro oncologist, I [am] focused on the pLGG cohort, [which] was designed to identify the clinical benefit and efficacy of tovarafinib.

What is the mechanism of action of tovorafenib?

Tovarafinib [is a] pan-RAF inhibitor. Many of our agents target a single step in the active pathways of these tumors, whereas as a pan RAF inhibitor, [tovarafinib] is targeting the pathway in its entirety. Another unique [characteristic of] the agent is that it’s once-weekly oral dosing, which is nice for patients and families in terms of quality of life.

What prior data have been reported with tovorafenib?

[Tovarafinib] seemed to provide clinical benefit and disease response in our patients with pLGG. That was promising in comparison with other agents that were currently being utilized in this setting.

What were the key data that were shared in the 3-year update?

The [median] TTNT being over 40 months is giving our patients and families a long period of not necessarily needing additional therapies. We also saw that most patients, once they stopped treatment after 26 cycles, were able to remain treatment-free for up to a year, and that the majority of patients too were able to finish the 26 cycles of therapy also. All of that is very promising in terms of the potential clinical benefit, the tolerability of this agent, and then, ideally, the ongoing disease control once the patients have come off of treatment.

What are the next steps for this research?

It’s going to continue to be to [monitor] these long-term outcomes in terms of how long we’re able to maintain disease control. There are other long term toxicities that we’re all interested in exploring as well. Those will really be critical next steps.

Another question in the setting of pLGG is this question of rebound growth that can happen after targeted agents are stopped. We’re going to be very comprehensive in also exploring the incidence of rebound growth and what that means for our patients and families with tovorafenibspecifically

In light of the updated data from FIREFLY-1, what is the current role of tovorafenib in pLGG?

Right now, we’re in the setting of an FDA indication for recurrent disease.² Many in our community are readily utilizing that [indication] and at the first step of disease recurrence or primary or upfront treatment failure. It’s certainly fitting nicely in that paradigm. There are ongoing studies that are exploring randomization between the agent with standard chemotherapy. [Determining] where this fits in the upfront treatment schema will be a next rational step as we’re thinking about how we’re utilizing this agent to treat our [patients].

References

1. Kline C, Hargrave D, Khong-Quang DA, 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.
2. FDA grants accelerated approval to tovorafenib for patients with relapsed or refractory BRAF-altered pediatric low-grade glioma. FDA. Updated May 22, 2024. Accessed January 2, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-tovorafenib-patients-relapsed-or-refractory-braf-altered-pediatric