Protein kinase c inhibitors for treatment of uveal melanoma
AssigneeNovartis AG
InventorsVesselina COOKE, Michael Scott VISSER, Andrew WYLIE, Padmaja YERRAMILLI-RAO, Xu ZHU
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Abstract
The present disclosure relates to use of a protein kinase C (PKC) inhibitor in the treatment or prevention of proliferative diseases. The disclosure also relates to corresponding pharmaceutical formulations, uses, methods, combinations, and related disclosure embodiments. The disclosure further relates to use of a pharmaceutical combination comprising a PKC inhibitor and another therapeutic agent, such as an MDM2 inhibitor, in the treatment or prevention of a proliferative disease.
Claims20
A method for treating uveal melanoma comprising administering to a subject in need of thereof 3-amino-N-(3-(4-amino-4-methylpiperidin-1-yl)pyridin-2-yl)-6-(3-(trifluoromethyl)pyridin-2-yl)pyrazine-2-carboxamide (Compound I) or a pharmaceutically acceptable salt thereof at a dose of from about 100 mg to about 1000 mg of Compound I daily.
The method of any one of the preceding claims, wherein the subject suffers from metastatic uveal melanoma.
The method of any one of the preceding claims, wherein the subject is an adult patient aged 18 years or older.
The method of any one of the preceding claims, wherein Compound I or a pharmaceutically acceptable salt thereof is orally administered.
The method of any one of the preceding claims, further comprising administering to the subject one or more other therapeutic agents.
The method of any one of the preceding claims, further comprising administering to the subject a mouse double minute 2 inhibitor (MDM2i).
The method of any one of the preceding claims, further comprising administering to the subject a therapeutically effective amount of mouse double minute 2 inhibitor (MDM2i) selected from (S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one (Compound II), (S)-1-(4-chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one (Compound III), and pharmaceutically acceptable salts thereof.
The method of any one of the preceding claims, further comprising administering to the subject a therapeutically effective amount of (S)-1-(4-chloro-phenyl)-7-isopropoxy-6-methoxy-2-(4-{methyl-[4-(4-methyl-3-oxo-piperazin-1-yl)-trans-cyclohexylmethyl]-amino}-phenyl)-1,4-dihydro-2H-isoquinolin-3-one (Compound III), or a pharmaceutically acceptable salt thereof.
The method of any one of the preceding claims, further comprising administering to the subject a therapeutically effective amount of (S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one (Compound II), or a pharmaceutically acceptable salt thereof.
The method of any one of the preceding claims, further comprising administering to the subject a therapeutically effective amount of (S)-5-(5-chloro-1-methyl-2-oxo-1,2-dihydro-pyridin-3-yl)-6-(4-chloro-phenyl)-2-(2,4-dimethoxy-pyrimidin-5-yl)-1-isopropyl-5,6-dihydro-1H-pyrrolo[3,4-d]imidazol-4-one (Compound II), or a pharmaceutically acceptable salt thereof once weekly.
The method of any one of the preceding claims, wherein the uveal melanoma comprises functional p53 or wild-type TP53.
The method of any one of the preceding claims, wherein the uveal melanoma or metastatic uveal melanoma is characterized by mutation of guanine nucleotide-binding protein G(q) subunit alpha (GNAQ) gene or guanine nucleotide-binding protein G(q) subunit 11 (GNA11) gene.
Dependencies are inferred from the claim text.