Methods for determining drug efficacy for the treatment of diffuse large b-cell lymphoma, multiple myeloma, and myeloid cancers

Patent metadata

Field	Value
Publication number	US-2016313300-A1
Application number	US-201415101869-A
Country	US
Kind code	A1
Filing date	Dec 5, 2014
Priority date	Dec 6, 2013
Publication date	Oct 27, 2016
Grant date	—

Abstract

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.

First claim

What is claimed is:

1 . A method of determining whether a compound is immunomodulatory, comprising:
(a) contacting a first cell with the compound;
wherein optionally the cell is a cancer cell, or
wherein optionally the cell is an immune cell;
(b) obtaining a first sample from the first cell from step (a); (c) determining the level of a biomarker in the first sample, and (d) comparing the level of the biomarker from step (c) to the level of the same protein obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound as an immunomodulatory compound.

2 . The method of claim 1 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an immunomodulatory compound.

3 . The method of claim 1 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an immunomodulatory compound.

4 . A method of treating a cancer, comprising the method of claim 2 or 3 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious as an immunomodulatory compound.

5 . The method of claim 1 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an immunomodulatory compound.

6 . The method of claim 1 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an immunomodulatory compound.

7 . A method of treating a cancer, comprising the method of claim 5 or 6 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated as unlikely to be efficacious as an immunomodulatory compound.

8 . A method of determining whether a compound is effective as an anti-tumor agent, comprising:
(a) contacting a first cell with the compound;
wherein optionally the cell is a cancer cell, or
wherein optionally the cell is an immune cell;
(b) obtaining a first sample from the first cell from step (a), (c) determining the level of a biomarker in the first sample; and (d) comparing the level of the biomarker from step (c) to the level of the same protein(s) obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound as an anti-tumor agent.

9 . The method of claim 8 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an anti-tumor agent.

10 . The method of claim 8 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious as an anti-tumor agent.

11 . A method of treating a cancer, comprising the method of claim 9 or 10 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious as an anti-tumor agent.

12 . The method of claim 8 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an anti-tumor agent.

13 . The method of claim 8 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious as an anti-tumor agent.

14 . A method of treating a cancer, comprising the method of claim 12 or 13 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated to be as unlikely to be efficacious as an anti-tumor agent.

15 . The method of any one of claims 1 to 14 , wherein the contacting in step (a) is in vitro.

16 . The method of any one of claims 1 to 14 , wherein the contacting in step (a) is in vivo.

17 . A method of assessing the efficacy of a compound in treating cancer, comprising:
(a) administering a compound to a subject having cancer; (b) obtaining a first sample from the subject; (c) determining the level of a biomarker in the first sample; and (d) comparing the level of the biomarker from step (c) to the level of the same protein obtained from a reference sample, wherein a change in the biomarker level as compared to the reference sample is indicative of the efficacy of the compound in treating the cancer.

18 . The method of claim 17 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious in treating the cancer.

19 . The method of claim 17 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is likely to be efficacious in treating the cancer.

20 . A method of treating a cancer, comprising the method of claim 18 or 19 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of the compound when the compound is indicated as likely to be efficacious in treating the cancer.

21 . The method of claim 17 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious in treating the cancer.

22 . The method of claim 17 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the compound is unlikely to be efficacious in treating the cancer.

23 . A method of treating a cancer, comprising the method of claim 21 or 22 , wherein the method further comprises (e) administering to the subject a therapeutically effective amount of a therapy other than the compound when the compound is indicated as unlikely to be efficacious in treating the cancer.

24 . A method of selecting a group of cancer subjects for the purposes of predicting clinical response, monitoring clinical response, or monitoring patient compliance to dosing by a compound, comprising:
(a) administering a compound to a subject; (b) obtaining a first sample from the subject; (c) determining the level of a biomarker in the first sample; and (d) diagnosing the subject as being likely to be responsive to the compound if the level of the biomarker in the first sample is different than the level in a reference sample.

25 . The method of claim 24 , wherein an increased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is likely to be responsive to the compound.

26 . The method of claim 24 , wherein a decreased level of the biomarker in the first sample as compared to the reference sample indicates that the subject is likely to be responsive to the compound.

27 . A method of treating a cancer, comprising the method of

Assignees

• Celgene Corp

Inventors

• Trotter Matthew William Burnell
• Hagner Patrick
• Havens Courtney G
• Chopra Rajesh
• Gandhi Anita
• Klippel Anke
• Wang Maria Yinglin
• Breider Mike
• Couto Suzana Sturlini
• Ren Yan
• Hollenbach Paul
• Macbeth Kyle

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61P25/00

  Drugs for disorders of the nervous system · CPC title

• A61P1/16

  for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics · CPC title

• G01N33/57557

  of other specific parts of the body, e.g. brain · CPC title