Method of treating cancer with IL-10 and antibodies that induce ADCC

• US 10,618,970 B2
• Filed: 02/01/2016
• Issued: 04/14/2020
• Est. Priority Date: 02/03/2015
• Status: Active Grant

• Current Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Original Assignee: Armo BioSciences Inc. (Eli Lilly and Company)
• Inventors: Mumm, John Brian, Chan, Ivan Ho
• Primary Examiner(s): Stoica, Elly-Gerald
• Application Number:
  US15/543,949
• Publication Number:
  US 20180002434A1
• Time in Patent Office: 1,534 Days
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 38/2066 IL-10
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61P 31/04 Antibacterial agents
• CPC Class Codes: C07K 16/2887 against CD20
• CPC Class Codes: C07K 2317/732 Antibody-dependent cellular cytotoxicity [ADCC]

Abstract

Methods of treating subjects having a proliferative disease, disorder, or condition, including cancer, via the administration of an IL-10 agent, including pegylated IL-10, in combination with an antibody capable of inducing anti-body-dependent cell-mediated cytotoxicity, are provided.

Claims

1. A method of treating cancer in a human subject, comprising administering to the subject:

a) an antibody capable of inducing antibody-dependent cell-mediated cytotoxicity (ADCC), wherein the antibody is selected from the group consisting of cetuximab, trastuzumab, zalutumumab, matuzumab, rituximab, trastuzumab, ipilumumab, and nimotuzumab, and

b) a therapeutically effective amount of an IL-10 agent, wherein the IL-10-agent is administered in an amount sufficient to maintain a mean IL-10 serum trough concentration of at least 1 ng/ml over a period of time of at least 1 week, wherein the mean IL-10 serum trough concentration is maintained for at least 90% of the period of time.

2. The method of claim 1, wherein the mean IL-10 serum trough concentration is at least 1.5 ng/mL.

3. The method of claim 2, wherein the mean IL-10 serum trough concentration is at least 2.0 ng/mL.

4. The method of claim 1, wherein the mean IL-10 serum trough concentration is maintained for at least 95% of the period of time.

5. The method of claim 4, wherein the mean IL-10 serum trough concentration is maintained for 100% of the period of time.

6. The method of claim 1, wherein the IL-10 agent is mature human IL-10.

7. The method of claim 1, wherein the cancer is a solid tumor or a hematological disorder.

8. The method of claim 1, wherein the cancer is selected from the group consisting of colon cancer, head and neck cancer, lung cancer, leukemia, lymphoma, and breast cancer.

9. The method of claim 1, wherein the IL-10 agent comprises at least one modification to form a modified IL-10 agent, wherein the modification does not alter the amino acid sequence of the IL-10 agent.

10. The method of claim 9, wherein the modified IL-10 agent is a PEG-IL-10 agent.

11. The method of claim 10, wherein the PEG-IL-10 agent comprises at least one PEG molecule covalently attached to at least one amino acid residue of at least one subunit of IL-10.

12. The method of claim 10, wherein the PEG-IL-10 agent comprises a mixture of mono-pegylated and di-pegylated IL-10.

13. The method of claim 10, wherein the PEG component of the PEG-IL-10 agent has a molecular mass from about 5 kDa to about 20 kDa.

14. The method of claim 1, wherein the administering of the IL-10 agent is by subcutaneous injection.

15. The method of claim 1, wherein the antibody and the IL-10 agent are administered simultaneously.

16. The method of claim 1, wherein the monoclonal antibody and the IL-10 agent are administered sequentially.

17. The method claim 1, further comprising administering at least one additional prophylactic or therapeutic agent.

18. The method of claim 17, wherein the prophylactic or therapeutic agent is a chemotherapeutic agent.