SC-9017: Day101-002 LOGGIC/FIREFLY-2: A Phase 3, Randomized, International Multicenter Trial Of DAY101 Monotherapy Versus Standard Of Care Chemotherapy In Patients With Pediatric Low-Grade Glioma Harboring An Activating RAF Alteration Requiring First-Line Systemic Therapy
SC-9017
What is the goal of the study?
LOGGIC/FIREFLY-2 (SC-9017) is a Phase 3, randomized trial evaluating the efficacy, safety, and tolerability of DAY101 vs. SoC chemotherapy in patients with pediatric low-grade glioma (pLGG) harboring an activating RAF alteration requiring first-line systemic therapy. DAY101 is an oral, type II pan-RAF kinase inhibitor that has been evaluated for safety in prior studies, PNOC-014 and PNOC-026. Randomization will be 1:1 between DAY101 (Arm 1) or SoC chemotherapy (Arm 2) regimens including COG–vincristine/carboplatin, SIOPe-LGG–vincristine/carboplatin, or vinblastine. The Arm 2 regimen will be determined prior to randomization and is the investigator’s choice. Our first-line therapy remains COG-V/C. There is a screening step prior to randomization. Tissue is required (sufficient FFPE or fresh frozen tumor tissue) or undergo biopsy. pLGG is the most common brain tumor diagnosed in children and BRAF fusions, in frame deletions, or point mutations are found in the majority of patients. Day101 inhibits both wild-type BRAF and CRAF/RAF1 kinases by directly inhibiting BRAF dimers, blocking downstream pERK signaling. It inhibits hyperactivated signaling resulting from BRAF fusions, including the KIAA1549:BRAF fusion, which is found in 70-80% of pilocytic astrocytomas. Notably, it is not associated with the paradoxical activation of the MAPK pathway reported for Type I BRAF inhibitors (vemurafenib) and in contrast to MEK inhibitors, DAY101 does not appear to have the severe dermatologic, cardiac, or ophthalmologic side effects. Early results from PNOC014 and PNOC026 show an ORR in patients with a confirmed RAF alteration of 63% (5/8 responses) and 64% (14/22 responses), respectively. The most common CTCAE Grade ≥ 3 treatment-emergent AEs, were rash (3 patients [12%]), anemia (3 patients [12%]), blood CPK increase (2 patients [8%]), and vomiting (2 patients [8%]). DAY101 is available in both tablet and powder for reconstitution as a liquid formulation.
Who can participate in the study?
Please contact the study team listed below to learn more.