Combination of a menin-ll1 inhibitor, a DNA intercalating agent and a pyrimidine analogue to treat a hematopoietic disorder
Patent Information
- Application Number
- HK62026126372
- Authority / Receiving Office
- HK · HK
- Patent Type
- Applications
- Current Assignee / Owner
- Priority Date
- 2023-07-18
- Filing Date
- 2026-07-20
- Publication Date
- 2026-10-09
- Estimated Expiration
- 2044-04-15
Smart Images
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Abstract
Description
Abstract This invention relates to a combination of a therapeutically effective amount of a menin-mixed lineage leukemia 1 (menin-MLL) inhibitor and a therapeutically effective amount of a DNA intercalator and a pyrimidine analog; and to a method of treating a subject diagnosed with cancer using such a combination.
Claims
CLAIMS 1. A combination of a therapeutically effective amount of (R)-N-ethyl-5-fluoro-N-isopropyl- 2-((5-(2-(6-((2-methoxyethyl)(methyl)amino)-2-methylhexan-3-yl)- 2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl)oxy)benzamide (Compound A):Compound A or a pharmaceutically acceptable salt or solvate thereof; and a therapeutically effective amount of a DNA intercalating agent and a pyrimidine analog (triple combination).
2. The combination according to claim 1 wherein Compound A or a pharmaceutically acceptable salt or solvate thereof, is a besylate salt (Compound A4-a)Compound A4-a or a solvate thereof.
3. The combination according to claim 2 wherein Compound A4-a or a solvate thereof is (R)-N-ethyl-5-fluoro-N-isopropyl- 2-((5-(2-(6-((2-methoxyethyl)(methyl)amino)-2-methylhexan-3-yl)-2,6-diazaspiro[3.4]octan- 6-yl)-1,2,4-triazin-6-yl)oxy)benzamide bis-besylate salt or a hydrate thereof.
4. The combination according to any one of claims 1-3 wherein the DNA intercalating agent is idarubicin, and the pyrimidine analog is cytarabine.
5. The combination according to any one of claims 1-3 wherein the DNA intercalating agent is daunorubicin, and the pyrimidine analog is cytarabine.
6. The combination according to any one of claims 1-3 wherein the DNA intercalating agent is doxorubicin, and the pyrimidine analog is cytarabine.
7. A pharmaceutical composition comprising a combination as claimed in any one of claims 1 to 6 and a pharmaceutically acceptable carrier.
8. A combination as claimed in any one of claims 1 to 6 or a pharmaceutical composition as claimed in claim 7 for use as a medicament.
9. A combination as claimed in any one of claims 1 to 6 or a pharmaceutical composition as claimed in claim 7 for use in the prevention or treatment, in particular treatment, of a hematopoietic disorder.
10. The combination or pharmaceutical composition for use according to claim 9 wherein the hematopoietic disorder harbours (i) one or more MLL1 (KMT2A) gene rearrangements or alterations (e.g., duplications or amplification) and / or NPM1 mutations plus (ii) a FLT3 mutation.
11. The combination or pharmaceutical composition for use according to claim 9 wherein the hematopoietic disorder harbours (i) one or more MLL1 (KMT2A) gene rearrangements plus (ii) a FLT3 mutation.
12. The combination or pharmaceutical composition for use according to claim 9, 10 or 11 wherein the hematopoietic disorder is acute myeloid leukemia (AML).
13. A method for treating a subject who has been diagnosed with a hematopoietic disorder comprising administering to the subject a combination of (R)-N-ethyl-5-fluoro-N-isopropyl-2-((5-(2-(6-((2-methoxyethyl)(methyl)amino)- 2-methylhexan-3-yl)-2,6-diazaspiro[3.4]octan-6-yl)-1,2,4-triazin-6-yl)oxy)benzamide (Compound A):Compound A or a pharmaceutically acceptable salt or solvate thereof; and a therapeutically effective amount of a DNA intercalating agent and a pyrimidine analog (triple combination).