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Msg  10308 of 10558  at  9/22/2022 9:37:20 AM  by

JBWIN


Building IP: BMY/SGEN Patent Appl. re "ANTI-PD-1 ANTIBODY IN COMBINATION WITH AN ANTI

 
United States Patent Application20220298243
Kind CodeA1
FARSACI; Benedetto ; et al.September 22, 2022

ANTI-PD-1 ANTIBODY IN COMBINATION WITH AN ANTI-CD30 ANTIBODY IN CANCER TREATMENT

Abstract

This disclosure provides methods for treating a tumor in a subject comprising administering to the subject an anti-PD-1 antibody and an anti-CD30 antibody. In some embodiments, the tumor is derived from a lymphoma (e.g., a Hodgkin lymphoma or a non-Hodgkin lymphoma). In certain embodiments, the anti-CD30 antibody is an antibody-drug conjugate, e.g., brentuximab vedotin.


Inventors:FARSACI; Benedetto; (Princeton, NJ) ; JOSEPHSON; Neil; (Bothell, WA) ; CAO; Anthony; (Sammamish, WA) ; HEISER; Ryan; (Lake Stevens, WA)
Applicant:
NameCityStateCountryType

Bristol-Myers Squibb Company
Seattle Genetics, Inc.

Princeton
Bothell

NJ
WA

US
US
Assignee:Bristol-Myers Squibb Company
Princeton
NJ

Seattle Genetics, Inc.
Bothell
WA

Family ID:1000006381287
Appl. No.:17/715875
Filed:April 7, 2022

Related U.S. Patent Documents

Application NumberFiling DatePatent Number
16306282Nov 30, 201811299543
PCT/US2017/035521Jun 1, 2017
17715875
62344866Jun 2, 2016
62382839Sep 2, 2016

Current U.S. Class:1/1
Current CPC Class:C07K 16/2878 20130101; A61K 2039/507 20130101; C07K 16/2818 20130101; C07K 2317/76 20130101; A61P 35/00 20180101; A61K 2039/505 20130101
International Class:C07K 16/28 20060101 C07K016/28; A61P 35/00 20060101 A61P035/00

Claims



1. A method of treating a human subject afflicted with a tumor derived from a non-Hodgkin lymphoma or a tumor derived from a Hodgkin lymphoma, comprising administering to the human subject a combination of: (a) an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 receptor (PD-1) and inhibits PD-1 activity ("anti-PD-1 antibody"); and (b) an antibody or an antigen-binding portion thereof that specifically binds to CD30 ("anti-CD30 antibody").

2. The method of claim 1, wherein (i) the non-Hodgkin lymphoma is relapsed or refractory non-Hodgkin lymphoma; (ii) the non-Hodgkin lymphoma is selected from diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), and any combination thereof (iii) the Hodgkin lymphoma is classical Hodgkin lymphoma (cHL); or (iv) the Hodgkin lymphoma is relapsed or refractory Hodgkin lymphoma, optionally relapsed HL after autologous stem cell transplant (ASCT) or relapsed HL in a human subject ineligible for ASCT.

3. The method of claim 1, wherein the non-Hodgkin lymphoma is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), and any combination thereof.

4. The method of claim 1, wherein the tumor comprises one or more cells that express CD30.

5. The method of claim 4, wherein at least about 0.1%, at least about 1%, at least about 2%, at least about 3%, at least about 4%, at least about 5%, at least about 6%, at least about 7%, at least about 8%, at least about 9%, at least about 10%, at least about 15%, at least about 20%, at least about 25%, at least about 30%, at least about 35%, at least about 40%, at least about 45%, at least about 50%, at least about 60%, at least about 70%, or at least about 80% of the tumor cells express CD30.

6. The method of claim 5, wherein (i) the anti-CD30 antibody cross-competes for binding to CD30 with cAC10, (ii) the anti-CD30 antibody comprises cAC10, or (iii) the anti-CD30 antibody is an anti-CD30 antibody conjugated to a therapeutic agent, optionally comprising an anti-neoplastic agent, such as an anti-mitotic agent, or monomethyl auristatin E (MMAE), and further optionally comprising a linker, such as a cleavable linker, between the therapeutic agent and the CD30 antibody.

7. The method of claim 1, wherein the anti-CD30 antibody is brentuximab vedotin.

8. The method of claim 1, wherein (i) the anti-PD-1 antibody cross-competes with nivolumab for binding to human PD-1; (ii) the anti-PD-1 antibody binds to the same epitope as nivolumab; (iii) the anti-PD-1 antibody is nivolumab; or (iv) the anti-PD-1 antibody is pembrolizumab.

9. The method of claim 1, wherein (i) the anti-PD-1 antibody is administered at a dose ranging from at least about 0.1 mg/kg to at least about 10.0 mg/kg body weight once about every 1, 2 or 3 weeks; (ii) the anti-PD-1 antibody is administered at a dose of at least about 3 mg/kg body weight once about every 2 weeks; (iii) the anti-PD-1 antibody is administered at a dose of at least about 3 mg/kg body weight once about every 3 weeks; (iv) the anti-PD-1 antibody or antigen-binding portion thereof is administered at a flat dose, optionally, at least about 200 mg, at least about 220 mg, at least about 240 mg, at least about 260 mg, at least about 280 mg, at least about 300 mg, at least about 320 mg, at least about 340 mg, at least about 360 mg, at least about 380 mg, at least about 400 mg, at least about 420 mg, at least about 440 mg, at least about 460 mg, at least about 480 mg, at least about 500 mg, or at least about 550 mg administered about once every 1, 2, 3, or 4 weeks.

10. The method of claim 1, wherein (i) the anti-CD30 antibody is administered at a dose ranging from at least about 0.1 mg/kg to at least about 180 mg/kg body weight once about every 1, 2 or 3 weeks; (ii) the anti-CD30 antibody is administered at a dose ranging from at least about 1.0 mg/kg to at least about 10 mg/kg body weight once about every 1, 2 or 3 weeks; (iii) the anti-CD30 antibody is administered at a dose of at least about 2 mg/kg body weight once about every 3 weeks; or (iv) the anti-CD30 antibody is administered at a dose of 1.8 mg/kg body weight once about every 3 weeks.

11. The method of claim 1, wherein (a) the anti-CD30 antibody is administered to the human subject on day 1 of a first 21-day cycle and the anti-PD-1 antibody is administered to the human subject on day 8 of the first 21-day cycle; and (b) optionally, a combination of the anti-CD30 antibody and the anti-PD-1 antibody is administered on day 1 of each of a second 21-day cycle, a third 21-day cycle, and a fourth 21-day cycle, wherein the second 21-day cycle, the third 21-day cycle, and the fourth 21-day cycle follow in succession after the first 21-day cycle, and wherein the anti-CD30 antibody is administered at a dose of about 1.8 mg/kg and the anti-PD-1 antibody is administered at a dose of about 3 mg/kg.

12. The method of claim 1, wherein the anti-PD-1 antibody and the anti-CD30 antibody are administered sequentially.

13. The method of claim 1, wherein the tumor comprises one or more cells that express PD-L1, PD-L2, or both PD-L1 and PD-L2.

14. The method of claim 1, wherein the human subject exhibits progression-free survival of at least about one month, at least about 2 months, at least about 3 months, at least about 4 months, at least about 5 months, at least about 6 months, at least about 7 months, at least about 8 months, at least about 9 months, at least about 10 months, at least about 11 months, at least about one year, at least about eighteen months, at least about two years, at least about three years, at least about four years, or at least about five years after the initial administration.

15. A kit comprising: (a) a dosage ranging from about 4 mg to about 500 mg of an anti-PD-1 antibody; (b) a dosage ranging from about 0.1 mg to about 500 mg of an anti-CD30 antibody; and (c) instructions for using the anti-PD-1 antibody and the anti-CD30 antibody according to the method of claim 1.

16. A method of treating a human subject afflicted with a tumor derived from a Hodgkin lymphoma, comprising administering to the human subject a combination of: (a) an anti-PD-1 antibody; and (b) an anti-CD30 antibody.

17. The method of claim 16, wherein (i) the Hodgkin lymphoma is classical Hodgkin lymphoma (cHL); or (ii) the Hodgkin lymphoma is relapsed or refractory Hodgkin lymphoma, optionally relapsed HL after autologous stem cell transplant (ASCT) or relapsed HL in a human subject ineligible for ASCT.

18. The method of claim 16, wherein the tumor comprises one or more cells that express CD30.

19. The method of claim 16, wherein (i) the anti-CD30 antibody cross-competes for binding to CD30 with cAC10, (ii) the anti-CD30 antibody comprises cAC10, or (iii) the anti-CD30 antibody is an anti-CD30 antibody conjugated to a therapeutic agent, optionally comprising an anti-neoplastic agent, such as an anti-mitotic agent, or monomethyl auristatin E (MMAE), and further optionally comprising a linker, such as a cleavable linker, between the therapeutic agent and the anti-CD30 antibody.

20. The method of claim 16, wherein the anti-CD30 antibody is brentuximab vedotin.
Description



CROSS REFERENCE TO RELATED APPLICATIONS

[0001] This application is a continuation application of U.S. application Ser. No. 16/306,282, which is the U.S. National Phase of International Application No. PCT/US2017/035521, filed on Jun. 1, 2017, which claims the benefit of U.S. Provisional Application Nos. 62/344,866, filed Jun. 2, 2016, and 62/382,839, filed on Sep. 2, 2016 each of which is incorporated by reference herein in its entirety.

FIELD OF THE DISCLOSURE

[0002] This disclosure relates to methods for treating a tumor in a subject comprising administering to the subject an anti-Programmed Death-1 (PD-1) antibody and an anti-CD30 antibody. In some embodiments, the tumor is derived from a lymphoma. In certain embodiments, the tumor is derived from a Hodgkin lymphoma, a non-Hodgkin lymphoma, or a combination thereof.

BACKGROUND OF THE DISCLOSURE

[0003] Human cancers harbor numerous genetic and epigenetic alterations, generating neoantigens potentially recognizable by the immune system (Sjoblom et al., (2006) Science 314:268-74). The adaptive immune system, comprised of T and B lymphocytes, has powerful anti-cancer potential, with a broad capacity and exquisite specificity to respond to diverse tumor antigens. Further, the immune system demonstrates considerable plasticity and a memory component. The successful harnessing of all these attributes of the adaptive immune system would make immunotherapy unique among all cancer treatment modalities.

[0004] Until recently, cancer immunotherapy had focused substantial effort on approaches that enhance anti-tumor immune responses by adoptive-transfer of activated effector cells, immunization against relevant antigens, or providing non-specific immune-stimulatory agents such as cytokines. In the past decade, however, intensive efforts to develop specific immune checkpoint pathway inhibitors have begun to provide new immunotherapeutic approaches for treating cancer, including the development of an antibody, ipilimumab (YERVOY.RTM.), that binds to and inhibits CTLA-4 for the treatment of patients with advanced melanoma (Hodi et al., 2010 N Engl J Med 363:711-23) and the development of antibodies, such as nivolumab and pembrolizumab (formerly lambrolizumab; USAN Council Statement, 2013), that bind specifically to the Programmed Death-1 (PD-1) receptor and block the inhibitory PD-1/PD-1 ligand pathway (Topalian et al., N Engl J Med 366:2443-54 (2012a); Topalian et al., Curr Opin Immunol 24:207-12 (2012b); Topalian et al., J Clin Oncol 32(10):1020-30 (2014); Hamid et al., N Engl J Med 369:134-144 (2013); Hamid and Carvajal, Expert Opin Biol Ther 13(6):847-61 (2013); and McDermott and Atkins, Cancer Med 2(5):662-73 (2013)).

[0005] Targeted therapy of multiple non-redundant molecular pathways regulating immune responses can enhance antitumor immunotherapy. However, not all combinations have acceptable safety and/or efficacy. There remains a need for combination therapies with an acceptable safety profile and high efficacy that enhance antitumor immune responses compared to monotherapy and other immunotherapy combinations.

SUMMARY OF THE DISCLOSURE

[0006] The present disclosure relates to a method of treating a subject afflicted with a tumor derived from a non-Hodgkin lymphoma comprising administering to the subject: (a) an antibody or an antigen-binding portion thereof that binds specifically to a Programmed Death-1 (PD-1) receptor and inhibits PD-1 activity ("anti-PD-1 antibody"); and (b) an antibody or an antigen-binding portion thereof that specifically binds to CD30 ("anti-CD30 antibody"). In some embodiments, the non-Hodgkin lymphoma is relapsed or refractory non-Hodgkin lymphoma. In certain embodiments, the non-Hodgkin lymphoma is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), peripheral T-cell lymphoma (PTCL), cutaneous T-cell lymphoma (CTCL), and any combination thereof.

[0007] The present disclosure further relates to a method of treating a subject afflicted with a tumor derived from a Hodgkin lymphoma comprising administering to the subject: (a) an anti-PD-1 antibody; and (b) an anti-CD30 antibody. In some embodiments, the Hodgkin lymphoma is classical Hodgkin lymphoma (cHL).

[0008] In some embodiments, the tumor comprises one or more cells that express CD30. In certain embodiments, at least 1% of the tumor cells express CD30.

[0009] In some embodiments, the anti-CD30 antibody cross-competes for binding to CD30 with cAC10. In some embodiments, the anti-CD30 antibody comprises cAC10. In some embodiments, the anti-CD30 antibody is an anti-CD30 antibody conjugated to a therapeutic agent ("anti-CD30 antibody-drug conjugate"). In certain embodiments, the therapeutic agent comprises monomethyl auristatin E (MMAE). In one particular embodiment, the anti-CD30 antibody is brentuximab vedotin.

[0010] In some embodiments, the anti-PD-1 antibody cross-competes with nivolumab for binding to human PD-1. In some embodiments, the anti-PD-1 antibody binds to the same epitope as nivolumab. In one particular embodiment, the anti-PD-1 antibody is nivolumab.

[0011] In certain embodiments, the anti-PD-1 antibody is administered at a dose of at least about 3 mg/kg body weight once about every 2 weeks. In some embodiments, the anti-CD30 antibody is administered at a dose of 1.8 mg/kg body weight once about every 3 weeks.

[0012] In some embodiments, the tumor comprises one or more cells that express PD-L1, PD-L2, or both.

[0013] In some embodiments, the subject received at least one prior chemotherapy treatment. In certain embodiments, the subject was not responsive to a prior chemotherapy treatment.

[0014] In some embodiments, the method further comprises administering a stem cell transplant to the patient after administering the anti-PD-1 antibody and the anti-CD30 antibody.

[0015] The present disclosure is further directed to a kit for treating a subject afflicted with a cancer, the kit comprising: (a) a dosage ranging from about 4 mg to about 500 mg of an anti-PD-1 antibody; (b) a dosage ranging from about 0.1 mg to about 500 mg of an anti-CD30 antibody; and (c) instructions for using the anti-PD-1 antibody and the anti-CD30 antibody in the method.

[0016] The present disclosure is further directed to a kit for treating a subject afflicted with a lymphoma, the kit comprising: (a) a dosage ranging from about 4 mg to about 500 mg of an anti-PD-1 antibody; (b) a dosage ranging from about 0.1 mg to about 500 mg of brentuximab vedotin; and (c) instructions for using the anti-PD-1 antibody and the brentuximab vedotin in the method.


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