Background
PD, cutaneous melanoma, Uveal melanoma, intraocular malignant tumour
CUTANEOUS MELANOMA, METASTATIC TUMOUR, MUTANT, SOMATIC MUTATION, UVEAL MELANOMA
Uveal melanoma (UM) is the most common primary intraocular malignant tumour in adults, involving the iris, ciliary body or choroid, and is biologically distinct from cutaneous melanoma in terms of driver genes and mutational burden [Somatic mutations affecting either one of two genes, guanine nucleotide-binding protein alpha-Q (GNAQ) or guanine nucleotide-binding protein alpha-11 (GNA11), that encode G-protein alpha subunits of heterotrimeric G-protein-coupled receptor (GPCR) complexes have been identified in >90% of patients with MUM [LXS196 is a potent, second-generation, oral PKC inhibitor designed with improved pharmaceutical properties compared with AEB071. LXS196 has a highly selective kinase profile affording increased tolerability in preclinical studies, with cellular activity restricted to UM cell lines containing mutant In this phase I trial, we aimed to evaluate the safety, preliminary efficacy, pharmacokinetics (PK) and pharmacodynamics (PD) of LXS196, and to determine the MTD and/or recommended dose for expansion (RDE) of LXS196 as a single agent in patients with MUM. Retrospective genomic analyses were conducted on baseline metastatic tumour biopsies.