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@ARTICLE{deBraud:274418,
      author       = {F. de Braud and C. Dooms and R. S. Heist and C. Lebbe and
                      M. Wermke and A. Gazzah and D. Schadendorf$^*$ and P.
                      Rutkowski and J. Wolf and P. A. Ascierto and I. Gil-Bazo and
                      S. Kato and M. Wolodarski and M. McKean and E. Muñoz
                      Couselo and M. Sebastian and A. Santoro and V. Cooke and L.
                      Manganelli and K. Wan and A. Gaur and J. Kim and G.
                      Caponigro and X.-M. Couillebault and H. Evans and C. D.
                      Campbell and S. Basu and M. Moschetta and A. Daud},
      title        = {{I}nitial {E}vidence for the {E}fficacy of {N}aporafenib in
                      {C}ombination {W}ith {T}rametinib in {NRAS}-{M}utant
                      {M}elanoma: {R}esults {F}rom the {E}xpansion {A}rm of a
                      {P}hase {I}b, {O}pen-{L}abel {S}tudy.},
      journal      = {Journal of clinical oncology},
      volume       = {41},
      number       = {14},
      issn         = {0732-183X},
      address      = {Alexandria, Va.},
      publisher    = {American Society of Clinical Oncology},
      reportid     = {DKFZ-2023-00585},
      pages        = {2651-2660},
      year         = {2023},
      note         = {2023 May 10;41(14):2651-2660},
      abstract     = {No approved targeted therapy for the treatment of patients
                      with neuroblastoma RAS viral (v-ras) oncogene homolog
                      (NRAS)-mutant melanoma is currently available.In this phase
                      Ib escalation/expansion study (ClinicalTrials.gov
                      identifier: NCT02974725), the safety, tolerability, and
                      preliminary antitumor activity of naporafenib (LXH254), a
                      BRAF/CRAF protein kinases inhibitor, were explored in
                      combination with trametinib in patients with
                      advanced/metastatic KRAS- or BRAF-mutant non-small-cell lung
                      cancer (escalation arm) or NRAS-mutant melanoma (escalation
                      and expansion arms).Thirty-six and 30 patients were enrolled
                      in escalation and expansion, respectively. During
                      escalation, six patients reported grade ≥3 dose-limiting
                      toxicities, including dermatitis acneiform (n = 2),
                      maculopapular rash (n = 2), increased lipase (n = 1), and
                      Stevens-Johnson syndrome (n = 1). The recommended doses for
                      expansion were naporafenib 200 mg twice a day plus
                      trametinib 1 mg once daily and naporafenib 400 mg twice a
                      day plus trametinib 0.5 mg once daily. During expansion, all
                      30 patients experienced a treatment-related adverse event,
                      the most common being rash $(80\%,$ n = 24), blood creatine
                      phosphokinase increased, diarrhea, and nausea $(30\%,$ n = 9
                      each). In expansion, the objective response rate, median
                      duration of response, and median progression-free survival
                      were $46.7\%$ $(95\%$ CI, 21.3 to 73.4; 7 of 15 patients),
                      3.75 $(95\%$ CI, 1.97 to not estimable [NE]) months, and
                      5.52 months, respectively, in patients treated with
                      naporafenib 200 mg twice a day plus trametinib 1 mg once
                      daily, and $13.3\%$ $(95\%$ CI, 1.7 to 40.5; 2 of 15
                      patients), 3.75 $(95\%$ CI, 2.04 to NE) months, and 4.21
                      months, respectively, in patients treated with naporafenib
                      400 mg twice a day plus trametinib 0.5 mg once
                      daily.Naporafenib plus trametinib showed promising
                      preliminary antitumor activity in patients with NRAS-mutant
                      melanoma. Prophylactic strategies aimed to lower the
                      incidence of skin-related events are under investigation.},
      cin          = {ED01},
      ddc          = {610},
      cid          = {I:(DE-He78)ED01-20160331},
      pnm          = {899 - ohne Topic (POF4-899)},
      pid          = {G:(DE-HGF)POF4-899},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36947734},
      doi          = {10.1200/JCO.22.02018},
      url          = {https://inrepo02.dkfz.de/record/274418},
}