Jordan Hansford, MD, clinical lead, Neuro-Oncology Group, Royal Children’s Hospital Melbourne, discusses the phase 2 FIREFLY-1 trial (NCT04775485), which is investigating the pan-RAF inhibitor tovorafenib (DAY101) in children and young adults patients with low-grade glioma.

 and the 2023 SNO Pediatric Neuro-Oncology Research Conference, FIREFLY-1 investigators presented efficacy and safety findings from this 3-arm phase 2 trial, Hansford says. FIREFLY-1 enrolled patients aged 6 months to 25 years with 

-altered tumors who experienced radiographic progression on at least 1 prior line of systemic therapy. Arm 1 of this trial (n = 77) enrolled patients with low-grade glioma harboring a known activating 

 V600E mutation. Arm 2 (n = 59) included patients with low-grade glioma harboring a known activating 

 alteration. Arm 3 is enrolling patients with locally advanced or metastatic solid tumors harboring a known activating 

 fusion whose disease relapsed after, progressed on, or was unresponsive to available therapies.

Patients in arm 1, including those with prior exposure to BRAF or MEK inhibitors, experienced marked responses to tovorafenib, Hansford emphasizes. In this arm, the overall response rate (ORR) per the Response Assessment in Neuro-Oncology – High-Grade Glioma (RANO-HGG) criteria was 67%, including a 6% complete response rate and a 61% partial response (PR) rate. Per RANO-HGG criteria, the clinical benefit rate (CBR) was 93%, and the CBR in patients who maintained a response or stable disease for at least 12 months was 71%. In addition, the ORR per the Response Assessment in Neuro-Oncology – Low-Grade Glioma criteria was 49%, including a PR rate of 26%.

The ORR per the Response Assessment in Pediatric Neuro-Oncology – Low-Grade Glioma criteria was 51%, including a PR rate of 25%.

In the safety population, which included patients from arms 1 and 2, the most common grade 3 or higher treatment-emergent adverse effects were maculopapular rash, fatigue, decreased appetite, and vomiting.

These data support the ongoing phase 3 FIREFLY-2 study (NCT05566795) of tovorafenib monotherapy vs standard of care chemotherapy in pediatric patients with 

-altered low-grade glioma, Hansford concludes.

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Jordan Hansford, MD, discusses the phase 2 FIREFLY-1 trial, which is investigating the pan-RAF inhibitor tovorafenib (DAY101) in children and young adults with low-grade glioma.

Jordan Hansford, MD

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Dr Hansford on the FIREFLY-1 Trial of Tovorafenib in Pediatric Low-Grade Glioma