Formulations of 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide

Patent metadata

Field	Value
Publication number	US-10449187-B2
Application number	US-201816040450-A
Country	US
Kind code	B2
Filing date	Jul 19, 2018
Priority date	Jan 8, 2016
Publication date	Oct 22, 2019
Grant date	Oct 22, 2019

Abstract

Provided herein are lyophilized formulations of 2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide or a stereisomer or mixture of stereisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof. Methods of using the formulations and dosage forms for treating, managing, and/or preventing cancer are also provided herein.

First claim

What is claimed:

1. A method of treating a cancer comprising administering to a mammal having cancer a lyophilized formulation comprising: Compound 1 (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide), or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, a buffer and a bulking agent, wherein the cancer is a solid tumor and the method further comprises administering calcium, calcitriol, and vitamin D supplementation.

2. The method of claim 1 , further comprising administering a therapeutically effective amount of a second active agent or a support care therapy.

3. The method of claim 2 , wherein the second active agent is 1) a therapeutic antibody that specifically binds to a cancer antigen or a pharmacologically active mutant thereof, 2) a hematopoietic growth factor, 3) a cytokine, 4) an anti-cancer agent, 5) an antibiotic, 6) a cox-2 inhibitor, 7) an immunomodulatory agent, 8) an immunosuppressive agent, or 9) a corticosteroid.

4. A method of treating a cancer comprising administering to a mammal having cancer a reconstituted formulation obtained from a lyophilized formulation and a diluent, wherein the lyophilized formulation comprises: Compound 1 (2-(4-chlorophenyl)-N-((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-5-yl)methyl)-2,2-difluoroacetamide), or a stereoisomer or mixture of stereoisomers, pharmaceutically acceptable salt, tautomer, prodrug, solvate, hydrate, co-crystal, clathrate, or polymorph thereof, a buffer and a bulking agent, wherein the cancer is a solid tumor and the method further comprises administering calcium, calcitriol, and vitamin D supplementation.

5. The method of claim 4 , wherein the method comprises administering the formulation intravenously.

6. The method of claim 4 , further comprising administering a therapeutically effective amount of a second active agent or a support care therapy.

7. The method of claim 6 , wherein the second active agent is 1) a therapeutic antibody that specifically binds to a cancer antigen or a pharmacologically active mutant thereof, 2) a hematopoietic growth factor, 3) a cytokine, 4) an anti-cancer agent, 5) an antibiotic, 6) a cox-2 inhibitor, 7) an immunomodulatory agent, 8) an immunosuppressive agent, or 9) a corticosteroid.

8. The method of claim 1 , wherein the cancer is a cancer of bladder, bone, brain, breast, cervix, chest, colon, endrometrium, esophagus, eye, head, kidney, liver, lymph nodes, lung, mouth, neck, ovaries, pancreas, prostate, rectum, stomach, testis, throat, or uterus.

9. The method of claim 1 comprising administering calcium, calcitriol, and vitamin D supplementation with the lyophilized formulation.

10. The method of claim 1 comprising administering calcium, calcitriol, and vitamin D supplementation prior to the lyophilized formulation.

11. The method of claim 4 , wherein the cancer is a cancer of bladder, bone, brain, breast, cervix, chest, colon, endrometrium, esophagus, eye, head, kidney, liver, lymph nodes, lung, mouth, neck, ovaries, pancreas, prostate, rectum, stomach, testis, throat, or uterus.

12. The method of claim 4 comprising administering calcium, calcitriol, and vitamin D supplementation with the reconstituted formulation.

13. The method of claim 4 comprising administering calcium, calcitriol, and vitamin D supplementation prior to the reconstituted formulation.

Assignees

• Celgene Corp

Inventors

• Hui Ho-Wah
• Pu Yu

Classifications

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61K39/395

  Antibodies (agglutinins A61K38/36 {; as drug carriers A61K47/50}); Immunoglobulins; Immune serum, e.g. antilymphocytic serum · CPC title

• A61K9/19 Primary

  lyophilised {, i.e. freeze-dried, solutions or dispersions (lyophilised products with subsequent particle size reduction A61K9/14; granules or pellets made by lyphilisation A61K9/1682; solid oral dosage forms made by lyophilisation A61K9/2095; lyophilisation additives A61K47/00)} · CPC title