Antiproliferative compounds and bispecific antibody against BCMA and CD3 for combined use

Patent metadata

Field	Value
Publication number	US-11439637-B2
Application number	US-201916419971-A
Country	US
Kind code	B2
Filing date	May 22, 2019
Priority date	May 23, 2018
Publication date	Sep 13, 2022
Grant date	Sep 13, 2022

Abstract

Provided herein is are methods of using 4-(4-(4-(((2-(2,6-dioxopiperidin-3-yl)-1-oxoisoindolin-4-yl)oxy)methyl)benzyl)piperazin-1-yl)-3-fluorobenzonitrile, or an enantiomer, a mixture of enantiomers, a tautomer, or a pharmaceutically acceptable salt thereof and a bispecific antibody specifically binding to human B cell maturation antigen (BCMA) and to human CD3ε (CD3) provided herein, in treating, preventing or managing multiple myeloma.

First claim

What is claimed is:

1. A method of treating multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 1

or an enantiomer, mixture of enantiomers, tautomer, isotopolog, or pharmaceutically acceptable salt thereof;

in combination with a bispecific antibody comprising a first binding part specifically binding to human B cell maturation antigen (BCMA) and a second binding part specifically binding to human CD3ε (CD3), characterized in that said first binding part comprises a VH region comprising a CDR1H region of SEQ ID NO:21, a CDR2H region of SEQ ID NO:22 and a CDR3H region of SEQ ID NO:17 and a VL region comprising a CDR3L region of SEQ ID NO:20 and a CDR1L and CDR2L region combination selected from the group of
i) CDR1L region of SEQ ID NO:23 and CDR2L region of SEQ ID NO:24,
ii) CDR1L region of SEQ ID NO:25 and CDR2L region of SEQ ID NO:26, or
iii) CDR1L region of SEQ ID NO:27 and CDR2L region of SEQ ID NO:28.

2. A method of treating multiple myeloma comprising administering to a patient in need thereof a therapeutically effective amount of a compound of formula 2

or a tautomer, isotopolog, or pharmaceutically acceptable salt thereof;

in combination with a bispecific antibody comprising a first binding part specifically binding to human B cell maturation antigen (BCMA) and a second binding part specifically binding to human CD3ε (CD3), characterized in that said first binding part comprises a VH region comprising a CDR1H region of SEQ ID NO:21, a CDR2H region of SEQ ID NO:22 and a CDR3H region of SEQ ID NO:17 and a VL region comprising a CDR3L region of SEQ ID NO:20 and a CDR1L and CDR2L region combination selected from the group of
i) CDR1L region of SEQ ID NO:23 and CDR2L region of SEQ ID NO:24,
ii) CDR1L region of SEQ ID NO:25 and CDR2L region of SEQ ID NO:26, or
iii) CDR1L region of SEQ ID NO:27 and CDR2L region of SEQ ID NO:28.

3. The method of claim 1 , wherein the multiple myeloma is relapsed, refractory or resistant.

4. The method of claim 3 , wherein the multiple myeloma is refractory or resistant to lenalidomide.

5. The method of claim 3 , wherein the multiple myeloma is refractory or resistant to pomalidomide.

6. The method of claim 1 , wherein the multiple myeloma is newly diagnosed multiple myeloma.

7. The method of claim 1 , wherein the multiple myeloma is plasma cell leukemia.

8. The method of claim 1 , wherein the compound is administered prior to the bispecific antibody.

9. The method of claim 1 , wherein the compound is administered concurrently with the bispecific antibody.

10. The method of claim 1 , wherein the compound is administered subsequent to the bispecific antibody.

11. The method of claim 1 , additionally comprising administering an additional active agent.

12. The method of claim 2 , wherein the multiple myeloma is relapsed, refractory or resistant.

13. The method of claim 12 , wherein the multiple myeloma is refractory or resistant to lenalidomide.

14. The method of claim 12 , wherein the multiple myeloma is refractory or resistant to pomalidomide.

15. The method of claim 2 , wherein the multiple myeloma is newly diagnosed multiple myeloma.

16. The method of claim 2 , wherein the multiple myeloma is plasma cell leukemia.

17. The method of claim 2 , wherein the compound is administered prior to the bispecific antibody.

18. The method of claim 2 , wherein the compound is administered concurrently with the bispecific antibody.

19. The method of claim 2 , wherein the compound is administered subsequent to the bispecific antibody.

20. The method of claim 2 , additionally comprising administering an additional active agent.

Assignees

• Celgene Corp

Inventors

• Pierce Daniel W
• Wong Lilly L

Classifications

• A61K2300/00

  Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 · CPC title

• A61P35/02

  specific for leukemia · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K45/06

  Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca · CPC title

• C07K16/2809 Primary

  against the T-cell receptor (TcR)-CD3 complex · CPC title