Tovorafenib Maintains Durable Clinical Benefit in Relapsed/Refractory Pediatric Low-Grade Glioma: Part 2

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Cassie Kline, MD, MAS, discusses updated data on rebound tumor growth and treatment-free interval among patients on the FIREFLY-1 study who entered the drug-free observation period.

Dr Kline is a pediatric neuro-oncologist at the Children's Hospital of Philadelphia and is the director of clinical research for the pediatric neuro-oncology group. 

Additionally, when we look at low-grade glioma outcomes, and certainly when we look at what happens when patients stop targeted treatment, we also want to look at rebound tumor growth, so how quickly does the tumor grow once you take the brakes off with the targeted therapy or stopping? And what we found was that there was minimal tumor rebound in patients when we followed them for 6 months off therapy. Again, we're looking at that N of 38 that entered the drug-free observation period.  

So specifically, we saw about a third or 12 patients out of the 39 that had an increase in tumor signs of at least 25% in the first 6 months. Of those 4 were BRAF V600E patients. But what's important to note is that even in the setting of the rebound growth, the majority of patients actually still had tumor size and tumor change that was below the baseline of their tumor size when they came into the study.  

And then we had 8 patients that did go on to have retreatment with tovorafenib, and of those, we were able to see some early signs of repeat efficacy. When we look at the maximal tumor change, after restarting tovorafenib, we saw a tumor shrinkage median value of about 38% and patients that were being treated for a median duration of about 9 months or 10.5 cycles of tovorafenib therapy.  

And then when we look at treatment-free interval, once patients have entered the drug-free observation period, the majority or 77% were able to achieve at least a 12-month treatment-free interval, and the end point of the treatment-free interval was actually not reached when we looked at this analysis.  

In conclusion, the updated 3-year analysis for FIREFLY-1, which looked at tovorafenib as a type II RAF inhibitor given once weekly in children, adolescents, and young adults with recurrent/refractory pediatric low-grade glioma showed us that 77% of patients who went into an observation period had a treatment-free interval of at least 12 months or more. They had a prolonged median time to next treatment of 42.6 months with minimal tumor rebound after drugs stop, early evidence of tovorafenib retreatment activity and no new safety signals. All of which is hopefully coming together to support tovorafenib as an effective therapy for recurrent refractory pediatric low-grade glioma. 

Source:  

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.