%0 Journal Article
%A de Braud, Filippo
%A Dooms, Christophe
%A Heist, Rebecca S
%A Lebbe, Celeste
%A Wermke, Martin
%A Gazzah, Anas
%A Schadendorf, Dirk
%A Rutkowski, Piotr
%A Wolf, Jürgen
%A Ascierto, Paolo A
%A Gil-Bazo, Ignacio
%A Kato, Shumei
%A Wolodarski, Maria
%A McKean, Meredith
%A Muñoz Couselo, Eva
%A Sebastian, Martin
%A Santoro, Armando
%A Cooke, Vesselina
%A Manganelli, Luca
%A Wan, Kitty
%A Gaur, Anil
%A Kim, Jaeyeon
%A Caponigro, Giordano
%A Couillebault, Xuân-Mai
%A Evans, Helen
%A Campbell, Catarina D
%A Basu, Sumit
%A Moschetta, Michele
%A Daud, Adil
%T Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study.
%J Journal of clinical oncology
%V 41
%N 14
%@ 0732-183X
%C Alexandria, Va.
%I American Society of Clinical Oncology
%M DKFZ-2023-00585
%P 2651-2660
%D 2023
%Z 2023 May 10;41(14):2651-2660
%X 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
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:36947734
%R 10.1200/JCO.22.02018
%U https://inrepo02.dkfz.de/record/274418