%0 Journal Article %A van Tilburg, Cornelis Martinus %A Kilburn, Lindsay B %A Perreault, Sébastien %A Schmidt, Rene %A Azizi, Amedeo A %A Cruz-Martínez, Ofelia %A Zápotocký, Michal %A Scheinemann, Katrin %A Meeteren, Antoinette Y N Schouten-van %A Sehested, Astrid %A Opocher, Enrico %A Driever, Pablo Hernáiz %A Avula, Shivaram %A Ziegler, David S %A Capper, David %A Koch, Arend %A Sahm, Felix %A Qiu, Jiaheng %A Tsao, Li-Pen %A Blackman, Samuel C %A Manley, Peter %A Milde, Till %A Witt, Ruth %A Jones, David T W %A Hargrave, Darren %A Witt, Olaf %T 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. %J BMC cancer %V 24 %N 1 %@ 1471-2407 %C Heidelberg %I Springer %M DKFZ-2024-00242 %P 147 %D 2024 %Z #EA:B310#LA:B310# %X 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 %K BRAF (Other) %K Chemotherapy (Other) %K Child (Other) %K First-line (Other) %K MAPK (Other) %K Pediatric low-grade glioma (Other) %K Tovorafenib (Other) %K pLGG (Other) %F PUB:(DE-HGF)16 %9 Journal Article %$ pmid:38291372 %R 10.1186/s12885-024-11820-x %U https://inrepo02.dkfz.de/record/287439