Day One Biopharmaceuticals, now part of Servier Group, has completed enrollment in the global Phase 3 FIREFLY-2 trial evaluating OJEMDA (tovorafenib) versus standard chemotherapy as first-line treatment for RAF-altered pediatric low-grade glioma.
Written By: Mahathi Palivela, PharmD
Reviewed By: Pharmacally Editorial Team
Day One Biopharmaceuticals, now part of the Servier Group, has completed enrollment in the Phase 3 FIREFLY‑2 trial evaluating tovorafenib (OJEMDA) versus standard chemotherapy as first‑line systemic therapy for pediatric low‑grade glioma (pLGG). The global study is being conducted in collaboration with the European Society for Paediatric Oncology (SIOPe) Brain Tumour Group LOGGIC Consortium.
FIREFLY‑2 is assessing the efficacy, safety, and tolerability of once‑weekly oral tovorafenib in patients aged 6 months to 25 years with RAF‑altered pLGG requiring front‑line systemic treatment. The trial enrolled approximately 400 participants across nearly 140 sites in the United States, Canada, Europe, Australia, South America, the Middle East, and Asia. Patients are randomized to receive either tovorafenib or one of several standard‑of‑care chemotherapy regimens.
The study’s primary endpoint is overall response rate (ORR), including duration of response (DOR), assessed using RAPNO‑LGG criteria. Key secondary endpoints include progression‑free survival (PFS), event‑free survival (EFS), time to next treatment (TTNT), overall survival (OS), and patient‑reported outcomes. Preliminary insights are expected in 2027, with the primary efficacy analysis planned about 12 months after final patient enrollment.
Elly Barry, Chief Medical Officer at Day One, said the company aims to establish OJEMDA across all lines of therapy for BRAF‑altered pLGG by moving targeted treatment earlier in the disease course. She added that positive FIREFLY‑2 results could support a shift in the treatment paradigm for newly diagnosed patients who currently receive chemotherapy‑based first‑line therapy.
David K. Lee, CEO of Servier Pharmaceuticals, said this enrollment milestone reflects the combined scientific and global development capabilities following Servier’s acquisition of Day One and could help advance targeted therapies for children with pLGG.
OJEMDA is currently approved in the United States for patients aged 6 months and older with relapsed or refractory pLGG harboring a BRAF fusion, rearrangement, or BRAF V600 mutation, under the FDA’s accelerated approval pathway. The European Commission has granted conditional marketing authorization for OJEMDA as monotherapy for patients aged 6 months and older with pLGG harboring a BRAF fusion or rearrangement or BRAF V600 mutation whose disease has progressed after one or more prior systemic therapies, based on results from the Phase II FIREFLY‑1 trial. Ipsen holds the exclusive ex‑U.S. regulatory and commercial rights for tovorafenib, including in Europe.
Tovorafenib has received FDA Breakthrough Therapy and Rare Pediatric Disease designations, as well as Orphan Drug designation from the FDA for malignant glioma, and additional Orphan Drug designation from the European Commission for glioma treatment.
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About the Writer
Mahathi Palivela (LinkedIn) is pursuing PharmD and has a strong interest in Clinical Pharmacy and Patient safety. She is passionate about handling and analyzing patient data, and translating clinical insights into clear, meaningful summaries. She aims to apply this interest in Medical Writing and Pharmacovigilance, focusing on improving patient outcomes through careful data interpretation and communication.