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CA-3091161-C - B7-H4 ANTIBODY DOSING REGIMENS

CA3091161CCA 3091161 CCA3091161 CCA 3091161CCA-3091161-C

Abstract

The present disclosure provides methods of administering antibodies and antigen-binding fragments thereof that specifically bind to human B7-H4 to a subject in need thereof, for example, a cancer patient.

Inventors

  • Sandeep P. INAMDAR
  • Helen L. Collins
  • Xiang Zhang
  • Hong Xiang

Assignees

  • FIVE PRIME THERAPEUTICS, INC.

Dates

Publication Date
20260505
Application Date
20190221
Priority Date
20180221

Claims (20)

  1. WHAT IS CLAIMED: 1. Use of an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4 in the preparation of a medicament for treatment of a solid tumor in a human subject in an amount from about 0.005 to about 20 mg/kg, wherein the antibody or antigen-binding fragment comprises a heavy chain variable region (VH) complementarity determining region (CDR) 1 comprising the amino acid sequence of SEQ ID NO:5, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:6, a VH CDR3 comprising the amino acid sequence of SEQ ID NO:7, a light chain variable region (VL) CDRl comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO:10.
  2. 2. Use of an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4 in the preparation of a medicament for treatment of a solid tumor in a human subject in an amount from about 0.005 to about 20 mg/kg, wherein the medicament comprises (i) antibodies or antigen-binding fragments thereof comprising a VH CDRl comprising the amino acid sequence of SEQ ID NO:5, a VH CDR2 comprising the amino acid sequence of SEQ ID NO:6, a VH CDR3 comprising the amino acid sequence of SEQ ID NO:7, a VL CDRl comprising the amino acid sequence of SEQ ID NO:8, a VL CDR2 comprising the amino acid sequence of SEQ ID NO:9, and a VL CDR3 comprising the amino acid sequence of SEQ ID NO: 10 and (ii) a pharmaceutically acceptable excipient, wherein at least 95% of the antibodies or antigen-binding fragments thereof in the medicament are afucosylated.
  3. 3. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 20 mg/kg.
  4. 4. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 10 mg/kg. Date Re1rue/Date Received 2023-10-18
  5. 5. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 3 mg/kg.
  6. 6. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 1 mg/kg.
  7. 7. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 0.3 mg/kg.
  8. 8. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 0.1 mg/kg.
  9. 9. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 0.03 mg/kg.
  10. 10. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 0.01 mg/kg.
  11. 11. The use of claim 1 or 2, wherein the amount of antibody or fragment thereof is about 0.005 mg/kg.
  12. 12. The use of any one of claims 1-11, wherein the amount of antibody or antigen-binding fragment thereof is for administration about once every three weeks.
  13. 13. The use of any one of claims 1-12, wherein the amount of antibody or antigen-binding fragment thereof is for administration intravenously.
  14. 14. The use of any one of claims 1-13, wherein B7-H4 has been detected in the solid tumor using immunohistochemistry (IHC) prior to the treatment. Date Re1rue/Date Received 2023-10-18
  15. 15. The use of any one of claims 1-14, wherein the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 11 and/or a VL comprising the amino acid sequence set forth in SEQ ID NO: 12.
  16. 16. The use of any one of claims 1-15, wherein the antibody or antigen-binding fragment comprises a heavy chain constant region and/or a light chain constant region.
  17. 17. The use of claim 16, wherein the heavy chain constant region is a human immunoglobulin IgG1 heavy chain constant region and/or wherein the light chain constant region is a human immunoglobulin IgGK light chain constant region.
  18. 18. The use of any one of claims 1-17, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain constant region comprising the amino acid sequence set forth in SEQ ID NO:25 and/or a light chain constant region comprising the amino acid sequence set forth in SEQ ID NO:23.
  19. 19. The use of any one of claims 1-18, wherein the antibody or antigen-binding fragment thereof comprises a heavy chain comprising the amino acid sequence set forth in SEQ ID NO:21 and/or a light chain comprising the amino acid sequence set forth in SEQ ID NO:22.
  20. 20. The use of any one of claims 1-19, wherein the antibody or antigen-binding fragment thereof is a human antibody or antigen-binding fragment thereof.

Description

WO 2019/165075 PCT /0S2019/018963 B7-H4 ANTIBODY DOSING REGIMENS 1. FIELD [0001] The present disclosure relates generally to methods of administering antibodies [0002] that specifically bind to human B7-H4 for the treatment of diseases such as cancer. Advantageous dose regimens are provided. 2. BACKGROUND B7-H4 (also known as B7x, B7-S1, and VTCNl) is an immune regulatory molecule that shares homology with other B7 family members, include PD-Ll. It is a type I transmembrane protein comprised of both IgV and IgC ectodomains. While B7-H4 expression in healthy tissues is relatively limited at the protein level, B7-H4 is expressed in several solid tumors such as gynecological carcinomas of the breast, ovary, and endometrium. Expression ofB7-H4 in tumors tends to correlate with poor prognosis. The receptor for B7-H4 is unknown, but it is believed to be expressed on T cells. B7-H4 is believed to directly inhibit T cell activity. [0003] Given the expression and function ofB7-H4, antibodies that specifically bind to [0004] B7-H4 are being developed for therapies involving the modulation ofB7-H4 activity, e.g., for the treatment of cancer. Accordingly, there is a need for dosing regimens for effective administration of such antibodies. 3. SUMMARY Methods of administering B7-H4 antibodies and antigen-binding fragments thereof using a therapeutically effective dose regimen are provided herein. [0005] In certain aspects, a method of treating a solid tumor in a human subject comprises administering to the subject about 0.005 to about 20 mg/kg of an antibody or antigen-binding fragment thereof that specifically binds to human B7-H4 and comprises the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDRl, VL CDR2, and VL CDR3 sequences of the 20502 antibody. [0006] In certain aspects, a method of treating a solid tumor in a human subject comprises administering to the subject a pharmaceutical composition comprising (i) WO 2019/165075 PCT /0S2019/018963 antibodies or antigen-binding fragments thereof, wherein the antibodies or antigenbinding fragments thereof specifically bind to human B7-H4 and comprise the heavy chain variable region (VH) complementarity determining region (CDR) 1, VH CDR2, VH CDR3 and light chain variable region (VL) CDRl, VL CDR2, and VL CDR3 sequences of the 20502 antibody and (ii) a pharmaceutically acceptable excipient, wherein at least 95% of the antibodies or antigen-binding fragments thereof in the composition are afucosylated, and wherein about 0.005 to about 20 mg/kg of the antibodies or antigen-binding fragments thereof are administered. [0007] In certain aspects, the CDRs are the Kabat-defined CDRs, the Chothia-defined CDRs, or the AbM-defined CDRs. In certain aspects, the VH CDRl, VH CDR2, VH CDR3, VL CDRl, VL CDR2, and CDR3 sequences comprise the amino acid sequences set forth in SEQ ID NOs:5-10, respectively. [0008] In certain aspects, about 20 mg/kg or 20 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 10 mg/kg or 10 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 3 mg/kg or 3 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 1 mg/kg or 1 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 0.3 mg/kg or 0.3 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about O .1 mg/kg or O .1 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, wherein about 0.03 mg/kg or 0.03 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 0.01 mg/kg or 0.01 mg/kg of the antibody or antigen-binding fragment thereof is administered to the subject. In certain aspects, about 0.005 mg/kg or 0.005 mg/kg of the antibody or antigenbinding fragment thereof is administered to the subject. [0009] In certain aspects, the antibody or antigen-binding fragment thereof is administered about once every three weeks. [0010] In certain aspects, the antibody or antigen-binding fragment thereof is administered intravenously. [0011] In certain aspects, B7-H4 has been detected in the solid tumor using immunohistochemistry (IHC) prior to the administration. WO 2019/165075 PCT /0S2019/018963 [0012] In certain aspects, the antibody or antigen-binding fragment thereof comprises a VH comprising the amino acid sequence set forth in SEQ ID NO: 11 and/or a VL comprising the amino acid sequence set forth in SEQ ID N0:12. In certain aspects, the antibody or antigen-binding fragment comprises a heavy chain constant region and/or a light chain constant region. In certain aspects, the heavy chain constant region is a human immunog