TY  - JOUR
AU  - de Braud, Filippo
AU  - Dooms, Christophe
AU  - Heist, Rebecca S
AU  - Lebbe, Celeste
AU  - Wermke, Martin
AU  - Gazzah, Anas
AU  - Schadendorf, Dirk
AU  - Rutkowski, Piotr
AU  - Wolf, Jürgen
AU  - Ascierto, Paolo A
AU  - Gil-Bazo, Ignacio
AU  - Kato, Shumei
AU  - Wolodarski, Maria
AU  - McKean, Meredith
AU  - Muñoz Couselo, Eva
AU  - Sebastian, Martin
AU  - Santoro, Armando
AU  - Cooke, Vesselina
AU  - Manganelli, Luca
AU  - Wan, Kitty
AU  - Gaur, Anil
AU  - Kim, Jaeyeon
AU  - Caponigro, Giordano
AU  - Couillebault, Xuân-Mai
AU  - Evans, Helen
AU  - Campbell, Catarina D
AU  - Basu, Sumit
AU  - Moschetta, Michele
AU  - Daud, Adil
TI  - 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.
JO  - Journal of clinical oncology
VL  - 41
IS  - 14
SN  - 0732-183X
CY  - Alexandria, Va.
PB  - American Society of Clinical Oncology
M1  - DKFZ-2023-00585
SP  - 2651-2660
PY  - 2023
N1  - 2023 May 10;41(14):2651-2660
AB  - 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
LB  - PUB:(DE-HGF)16
C6  - pmid:36947734
DO  - DOI:10.1200/JCO.22.02018
UR  - https://inrepo02.dkfz.de/record/274418
ER  -