EZH2 INHIBITORS FOR TREATING CANCER

• US 20190328743A1
• Filed: 06/16/2017
• Published: 10/31/2019
• Est. Priority Date: 06/17/2016
• Status: Active Grant

• Current Assignee: Epizyme, Inc. (Ipsen Sa)
• Original Assignee: Epizyme, Inc. (Ipsen Sa)
• Inventors: RIBICH, Scott, THOMENIUS, Michael
• Granted Patent: US 11,147,819 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 31/4375 the heterocyclic ring system containing a six-membered ring having nitrogen as a ring heteroatom, e.g. quinolizines, naphthyridines, berberine, vincamine
• CPC Class Codes: A61K 31/4412 having oxo groups directly attached to the heterocyclic ring
• 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 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/519 ortho- or peri-condensed with heterocyclic rings
• CPC Class Codes: A61K 31/52 Purines, e.g. adenine
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/573 substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
• CPC Class Codes: A61K 38/177 Receptors; Cell surface antigens; Cell surface determinants
• CPC Class Codes: A61K 39/395 Antibodies agglutinins A61K38/36 ; as drug carriers A61K47/50; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
• CPC Class Codes: A61K 45/06 Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
• CPC Class Codes: A61K 9/0053 Mouth and digestive tract, i.e. intraoral and peroral administration rectal administration A61K9/0031
• CPC Class Codes: A61P 35/00 Antineoplastic agents

Abstract

The present disclosure relates to compositions comprising inhibitors of human histone methyltransferase EZH2 and one or more other therapeutic agents, for example, modulators of CD40 pathway activity, such as CD40 agonists, and methods of combination therapy for administering to subjects in need thereof for the treatment of cancer.

Claims

1. A method for treating a cancer in a subject in need thereof comprising administering a therapeutically effective amount of an EZH2 inhibitor and a second therapeutic agent.

2. The method of claim 1, wherein the cancer is germinal center-derived lymphoma, e.g., an EZH2 wild type germinal center B-cell lymphoma.

3. The method of claim 1, wherein the second therapeutic agent is a CD40 agonist.

4. The method of claim 3, wherein the CD40 agonist comprises CD40L, or a CD40-binding fragment of CD40L, an agonistic CD40 antibody or an agonistic CD40 antibody fragment, CP870,893 (Pfizer), SGN-40, or a CD40 agonist peptide, or a small molecule.

5. The method of claim 1, wherein the EZH2 inhibitor is administered orally.

6. The method of claim 1, wherein the subject is a human being.

7. The method of claim 1, wherein the EZH2 inhibitor is of Formula (I):

8. The method of claim 1, wherein the EZH2 inhibitor is EPZ-6438 having the following formula:

9. The method of claim 1, wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg to about 3200 mg daily.

10. The method of claim 1, wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg BID to about 1600 mg BID.

11. The method of claim 1, wherein the EZH2 inhibitor is administered to the subject at a dose of about 100 mg BID, 200 mg BID, 400 mg BID, 800 mg BID, or about 1600 mg BID.

12. The method of claim 1, wherein the EZH2 inhibitor is:

13. The method of claim 1, wherein the EZH2 inhibitor is:

14. The method of claim 1, further comprising administering a therapeutically effective amount of an agent listed in TABLE 1.

15. The method of claim 3, wherein the CD40 agonist comprises an anti CD40 antibody or an anti CD40-antibody fragment.

16. The method of claim 1, wherein the EZH2 inhibitor and the second therapeutic agent are administered simultaneously or sequentially.

17. The method of claim 1, wherein the EZH2 inhibitor is administered prior to administration of the second therapeutic agent.

18. The method of claim 1, wherein the second therapeutic agent is administered prior to administration of the EZH2 inhibitor.