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@ARTICLE{vanTilburg:287439,
      author       = {C. M. van Tilburg$^*$ and L. B. Kilburn and S. Perreault
                      and R. Schmidt and A. A. Azizi and O. Cruz-Martínez and M.
                      Zápotocký and K. Scheinemann and A. Y. N. S. Meeteren and
                      A. Sehested and E. Opocher and P. H. Driever and S. Avula
                      and D. S. Ziegler and D. Capper$^*$ and A. Koch and F.
                      Sahm$^*$ and J. Qiu and L.-P. Tsao and S. C. Blackman and P.
                      Manley and T. Milde$^*$ and R. Witt$^*$ and D. T. W.
                      Jones$^*$ and D. Hargrave and O. Witt$^*$},
      title        = {{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.},
      journal      = {BMC cancer},
      volume       = {24},
      number       = {1},
      issn         = {1471-2407},
      address      = {Heidelberg},
      publisher    = {Springer},
      reportid     = {DKFZ-2024-00242},
      pages        = {147},
      year         = {2024},
      note         = {#EA:B310#LA:B310#},
      abstract     = {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
                      $67\%.$ Tumor response was independent of histologic
                      subtype, BRAF alteration type (fusion vs. mutation), number
                      of prior lines of therapy, and prior MAPK-pathway inhibitor
                      use.LOGGIC/FIREFLY-2 is a two-arm, randomized, open-label,
                      multicenter, global, phase 3 trial to evaluate the efficacy,
                      safety, and tolerability of tovorafenib monotherapy vs.
                      current standard of care (SoC) chemotherapy in patients < 25
                      years of age with pLGG harboring an activating RAF
                      alteration who require first-line systemic therapy. Patients
                      are randomized 1:1 to either tovorafenib, administered once
                      weekly at 420 mg/m2 (not to exceed 600 mg), or
                      investigator's choice of prespecified SoC chemotherapy
                      regimens. The primary objective is to compare ORR between
                      the two treatment arms, as assessed by independent review
                      per RANO-LGG criteria. Secondary objectives include
                      comparisons of progression-free survival, duration of
                      response, safety, neurologic function, and clinical benefit
                      rate.The promising tovorafenib activity data,
                      CNS-penetration properties, strong scientific rationale
                      combined with the manageable tolerability and safety profile
                      seen in patients with pLGG led to the SIOPe-BTG-LGG working
                      group to nominate tovorafenib for comparison with SoC
                      chemotherapy in this first-line phase 3 trial. The efficacy,
                      safety, and functional response data generated from the
                      trial may define a new SoC treatment for newly diagnosed
                      pLGG.ClinicalTrials.gov: NCT05566795. Registered on October
                      4, 2022.},
      keywords     = {BRAF (Other) / Chemotherapy (Other) / Child (Other) /
                      First-line (Other) / MAPK (Other) / Pediatric low-grade
                      glioma (Other) / Tovorafenib (Other) / pLGG (Other)},
      cin          = {B310 / HD01 / BE01 / B300 / B360},
      ddc          = {610},
      cid          = {I:(DE-He78)B310-20160331 / I:(DE-He78)HD01-20160331 /
                      I:(DE-He78)BE01-20160331 / I:(DE-He78)B300-20160331 /
                      I:(DE-He78)B360-20160331},
      pnm          = {312 - Funktionelle und strukturelle Genomforschung
                      (POF4-312)},
      pid          = {G:(DE-HGF)POF4-312},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38291372},
      doi          = {10.1186/s12885-024-11820-x},
      url          = {https://inrepo02.dkfz.de/record/287439},
}