Compositions and methods for treating cancer with a combination of programmed death receptor (PD-1) antibodies and a CXCR2 antagonist
The present invention relates to methods of treating a cell proliferation disorder (e.g., cancer) comprising administering: (a) a compound having the Formula (I), wherein R 1 or R 2 are as herein defined, or a pharmaceutically acceptable salt thereof; and (b) an anti-human PD-1 antibody or antigen binding fragment thereof to a human patient in need thereof. Also disclosed are therapeutic combinations and kits containing such agents for the treatment of cancers.
1. A method of treating prostate cancer, comprising administering:
(a) a compound having the Formula I
wherein R 1 are R 2 are independently H or C 1 -C 5 alkyl or a pharmaceutically acceptable salt thereof; and
(b) an anti-human PD-1 antibody or antigen binding fragment thereof to a human patient in need thereof.
2. The method of claim 1 , wherein the prostate cancer is metastatic castrate-resistant prostate cancer.
3. The method of claim 1 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.
4. The method of claim 3 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.
5. The method of claim 3 , wherein the compound of Formula I is
or a pharmaceutically acceptable salt thereof.
6. The method of claim 1 , wherein the human patient is administered:
(a) 200 mg or 240 mg of the anti-human PD-1 antibody or antigen binding fragment thereof and from 5 to 200 mg of the compound of Formula I or a pharmaceutically acceptable salt thereof; or
(b) 2 mg/kg of an anti-human PD-1 antibody or antigen binding fragment thereof and from 5 to 200 mg of the compound of Formula I or a pharmaceutically acceptable salt thereof,
wherein the anti-human PD-1 antibody or antigen binding fragment thereof is administered once every three weeks and the compound of Formula I or a pharmaceutically acceptable salt thereof is administered once daily or twice daily.
7. The method of claim 1 , wherein the anti-human PD-1 antibody or antigen binding fragment thereof comprises three light chain CDRs of SEQ ID NO:1, SEQ ID NO:2 and SEQ ID NO:3 and three heavy chain CDRs of SEQ ID NO:6, SEQ ID NO:7 and SEQ ID NO:8.
8. The method of claim 1 , wherein the anti-human PD-1 antibody or antigen binding fragment thereof comprises a V L region which comprises the amino acid sequence set forth in SEQ ID NO:4, and a V H region which comprises the amino acid sequence set forth in SEQ ID NO:9.
9. The method of claim 1 , wherein the anti-human PD-1 antibody or antigen binding fragment thereof comprises a light chain comprising or consisting of a sequence of amino acids as set forth in SEQ ID NO:5 and a heavy chain comprising or consisting of a sequence of amino acids as set forth in SEQ ID NO:10.
10. The method of claim 1 , wherein the anti-human PD-1 antibody or antigen binding fragment thereof is pembrolizumab.
11. The method of claim 1 , wherein the anti-human PD-1 antibody or antigen binding fragment thereof is nivolumab.