TY - JOUR AU - van Tilburg, Cornelis Martinus AU - Kilburn, Lindsay B AU - Perreault, Sébastien AU - Schmidt, Rene AU - Azizi, Amedeo A AU - Cruz-Martínez, Ofelia AU - Zápotocký, Michal AU - Scheinemann, Katrin AU - Meeteren, Antoinette Y N Schouten-van AU - Sehested, Astrid AU - Opocher, Enrico AU - Driever, Pablo Hernáiz AU - Avula, Shivaram AU - Ziegler, David S AU - Capper, David AU - Koch, Arend AU - Sahm, Felix AU - Qiu, Jiaheng AU - Tsao, Li-Pen AU - Blackman, Samuel C AU - Manley, Peter AU - Milde, Till AU - Witt, Ruth AU - Jones, David T W AU - Hargrave, Darren AU - Witt, Olaf TI - LOGGIC/FIREFLY-2: a phase 3, randomized trial of tovorafenib vs. chemotherapy in pediatric and young adult patients with newly diagnosed low-grade glioma harboring an activating RAF alteration. JO - BMC cancer VL - 24 IS - 1 SN - 1471-2407 CY - Heidelberg PB - Springer M1 - DKFZ-2024-00242 SP - 147 PY - 2024 N1 - #EA:B310#LA:B310# AB - Pediatric low-grade glioma (pLGG) is essentially a single pathway disease, with most tumors driven by genomic alterations affecting the mitogen-activated protein kinase/ERK (MAPK) pathway, predominantly KIAA1549::BRAF fusions and BRAF V600E mutations. This makes pLGG an ideal candidate for MAPK pathway-targeted treatments. The type I BRAF inhibitor, dabrafenib, in combination with the MEK inhibitor, trametinib, has been approved by the United States Food and Drug Administration for the systemic treatment of BRAF V600E-mutated pLGG. However, this combination is not approved for the treatment of patients with tumors harboring BRAF fusions as type I RAF inhibitors are ineffective in this setting and may paradoxically enhance tumor growth. The type II RAF inhibitor, tovorafenib (formerly DAY101, TAK-580, MLN2480), has shown promising activity and good tolerability in patients with BRAF-altered pLGG in the phase 2 FIREFLY-1 study, with an objective response rate (ORR) per Response Assessment in Neuro-Oncology high-grade glioma (RANO-HGG) criteria of 67 KW - BRAF (Other) KW - Chemotherapy (Other) KW - Child (Other) KW - First-line (Other) KW - MAPK (Other) KW - Pediatric low-grade glioma (Other) KW - Tovorafenib (Other) KW - pLGG (Other) LB - PUB:(DE-HGF)16 C6 - pmid:38291372 DO - DOI:10.1186/s12885-024-11820-x UR - https://inrepo02.dkfz.de/record/287439 ER -