Combination therapy comprising a mat2a inhibitor and a topoisomerase inhibitor, a splicing inhibitor sulfonamide, or a kif18 inhibitor
AssigneesIdeaya Biosciences, Inc., Glaxosmithkline Intellectual Property (No.4) Limited
InventorsMarcus M. FISCHER, Claire L. NEILAN, Kimberline Yang GERRICK, Anthony MAZUREK, Jenny Leigh LARAIO
Life of this patent
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Abstract
Provided herein is a combination of a methionine adenosyltransferase II alpha (MAT2A) inhibitor and a topoisomerase inhibitor, a splicing inhibitor sulfonamide, or a KIF18 inhibitor. Also provided are methods of using such combinations to treat diseases or disorders, for example, cancer.
Claims41
A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a MAT2A inhibitor and administering to the subject a therapeutically effective amount of a topoisomerase inhibitor, wherein the MAT2A inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- X is N or CH;
- R3 is C1-6 haloalkyl, halo, or C3-6 cycloalkyl;
- R2 is —NR4R5;
- R4 is hydrogen or C1-6 alkyl;
- R5 is hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
- and
- R1 is phenyl substituted with 0-2 halo.
A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a MAT2A inhibitor and administering to the subject a therapeutically effective amount of a splicing inhibitor sulfonamide (SPLAM), wherein the MAT2A inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- X is N or CH;
- R3 is C1-6 haloalkyl, halo, or C3-6 cycloalkyl;
- R2 is —NR4R5;
- R4 is hydrogen or C1-6 alkyl;
- R5 is hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
- and
- R1 is phenyl substituted with 0-2 halo.
A method of treating cancer in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a MAT2A inhibitor and administering to the subject a therapeutically effective amount of a KIF18 inhibitor, wherein the MAT2A inhibitor is a compound of Formula (I) or a pharmaceutically acceptable salt thereof:
- wherein
- X is N or CH;
- R3 is C1-6 haloalkyl, halo, or C3-6 cycloalkyl;
- R2 is —NR4R5;
- R4 is hydrogen or C1-6 alkyl;
- R5 is hydrogen, C1-6 alkyl, or C3-6 cycloalkyl;
- and
- R1 is phenyl substituted with 0-2 halo.
Use of a MAT2A inhibitor in the manufacture of a medicament for treating cancer, wherein the MAT2A inhibitor is used in combination with a topoisomerase inhibitor.
Use of a MAT2A inhibitor in the manufacture of a medicament for treating cancer, wherein the MAT2A inhibitor is used in combination with a SPLAM.
Use of a MAT2A inhibitor in the manufacture of a medicament for treating cancer, wherein the MAT2A inhibitor is used in combination with a KIF18 inhibitor.
A method of inhibiting tumor growth or slowing the rate of tumor growth in a subject having a MTAP-deficient cancer, the method comprising administration of a therapeutically effective amount of a MAT2A inhibitor and a therapeutically effective amount of a topoisomerase inhibitor, a SPLAM, or a KIF18 inhibitor.
A method of treating cancer in a subject in need thereof, the method comprising administering to the subject a therapeutically effective amount of a MAT2A inhibitor and a therapeutically effective amount of a topoisomerase inhibitor, a SPLAM, or a KIF18 inhibitor,
- wherein the subject is not previously treated with a MAT2A inhibitor.
Dependencies are inferred from the claim text.