COMBINATION THERAPY FOR TREATING CANCER

• US 20190315725A1
• Filed: 04/02/2019
• Published: 10/17/2019
• Est. Priority Date: 04/13/2012
• Status: Active Grant

• Current Assignee: Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Epizyme, Inc. (Ipsen Sa)
• Inventors: KEILHACK, Heike, KNUTSON, Sarah Kathleen, KUNTZ, Kevin Wayne
• Granted Patent: US 10,787,440 B2
• Time in Patent Office: Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/436 the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• CPC Class Codes: A61K 31/4433 containing a six-membered ring with oxygen as a ring hetero atom
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4745 condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines yohimbine derivatives, vinblastine A61K31/475; ergoline derivatives A61K31/48
• CPC Class Codes: A61K 31/53 having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine melarsoprol A61K31/555 ; with four nitrogen atoms A61K31/495
• CPC Class Codes: A61K 31/5355 Non-condensed oxazines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 31/675 having nitrogen as a ring hetero atom, e.g. pyridoxal phosphate
• CPC Class Codes: A61K 31/704 attached to a condensed carbocyclic ring system, e.g. sennosides, thiocolchicosides, escin, daunorubicin digitoxin A61K31/7048
• CPC Class Codes: A61K 31/7068 having oxo groups directly attached to the pyrimidine ring, e.g. cytidine, cytidylic acid
• CPC Class Codes: A61K 33/24 Heavy metals; Compounds thereof
• CPC Class Codes: A61K 33/243 Platinum; Compounds thereof
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 213/64 : attached in position 2 or 6
• CPC Class Codes: C07D 405/12 : linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 413/14 : containing three or more hetero rings

Abstract

The present invention relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, particularly anticancer agents such as prednisone, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Claims

1-11. -11. (canceled)

12. A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective dose of a compound of Formula (IIa):

13. The method of claim 12, wherein the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof, is administered prior to administration of said rituximab.

28. The method of claim 12, wherein said subject has demonstrated resistance to the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof when administered as a single agent.

34. The method of claim 12, wherein the cancer is lymphoma, leukemia, or melanoma.

38. The method of claim 34, wherein the cancer is follicular lymphoma.

39. The method of claim 12, wherein the cancer is resistant to at least one prior monotherapy.

40. The method of claim 12, wherein the cancer is resistant to at least one prior combination therapy.

41. The method of claim 12, wherein said subject has demonstrated resistance to rituximab when administered as a single agent.

42. The method of claim 12, wherein the compound of Formula (IIa) is Compound 44:

14-27. -27. (canceled)

29-33. -33. (canceled)

35-37. -37. (canceled)

43. A method of treating cancer comprising administering to a subject in need thereof a therapeutically effective dose of a compound of Formula (IIa):

44. The method of claim 43, wherein the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof, is administered prior to administration of said rituximab, said lenalidomide, or a combination of said rituximab and said lenalidomide.

45. The method of claim 43, wherein the cancer is resistant to at least one prior monotherapy.

46. The method of claim 43, wherein said subject has demonstrated resistance to the compound of Formula (IIa) or a pharmaceutically acceptable salt thereof when administered as a single agent.

47. The method of claim 43, wherein the cancer is resistant to at least one prior combination therapy.

48. The method of claim 43, wherein said subject has demonstrated resistance to lenalidomide when administered as a single agent.

49. The method of claim 43, wherein said subject has demonstrated resistance to rituximab when administered as a single agent.

50. The method of claim 43, wherein said subject has demonstrated resistance to rituximab and to lenalidomide when administered as single agents or in combination.

51. The method of claim 43, wherein the cancer is lymphoma, leukemia, or melanoma.

52. The method of claim 51, wherein the cancer is follicular lymphoma.

53. The method of claim 43, wherein the compound of Formula (IIa) is Compound 44: