Combination of anti-LAG-3 antibodies and anti-PD-1 antibodies to treat tumors
Provided are methods for clinical treatment of tumors (e.g., advanced solid tumors) using an anti-LAG-3 antibody in combination with an anti-PD-1 antibody.
1. A method of treating melanoma in a human patient, the method comprising administering to the patient an effective amount of each of:
(a) an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:3, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:5,
(b) an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 19, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:21,
wherein the method comprises at least one administration cycle, wherein the cycle is a period of two weeks, wherein for each of the at least one cycle, one dose of the anti-LAG-3 antibody is administered at a dose of 80 mg and one dose of the anti-PD-1 antibody is administered at a dose of 240 mg, and
wherein the patient has been previously treated with anti-PD-1 or anti-PD-L1 antibody therapy.
2. The method of claim 1 , further comprising the administration of an anti-CTLA-4 antibody.
3. The method of claim 1 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated for intravenous administration.
4. The method of claim 1 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated together.
5. The method of claim 1 , wherein the anti-PD-1 and anti-LAG-3 antibodies are formulated separately.
6. The method of claim 1 , wherein the treatment consists of up to 12 cycles.
7. The method of claim 1 , wherein the anti-PD-1 antibody is administered prior to administration of the anti-LAG-3 antibody.
8. The method of claim 1 , wherein the anti-PD-1 antibody is administered after administration of the anti-LAG-3 antibody.
9. The method of claim 1 , wherein the anti-PD-1 antibody is administered concurrently with the anti-LAG-3 antibody.
10. The method of claim 1 , wherein the anti-LAG-3 antibody comprises
(a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:7;
(b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:8;
(c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:9;
(d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:10;
(e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:11; and
(f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:12.
11. The method of claim 1 , wherein the anti-LAG-3 antibody comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs:3 and 5, respectively.
12. The method of claim 1 , wherein the anti-LAG-3 antibody comprises heavy and light chains comprising the sequences set forth in SEQ ID NOs: 1 and 2, respectively.
13. The method of claim 1 , wherein the anti-PD-1 antibody comprises
(a) a heavy chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:23;
(b) a heavy chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:24;
(c) a heavy chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:25;
(d) a light chain variable region CDR1 comprising the sequence set forth in SEQ ID NO:26;
(e) a light chain variable region CDR2 comprising the sequence set forth in SEQ ID NO:27; and
(f) a light chain variable region CDR3 comprising the sequence set forth in SEQ ID NO:28.
14. The method of claim 1 , wherein the anti-PD-1 antibody comprises heavy and light chain variable regions comprising the sequences set forth in SEQ ID NOs: 19 and 21, respectively.
15. The method of claim 1 , wherein the anti-PD-1 antibody comprises heavy and light chains comprising the sequences as set forth in SEQ ID NOs: 17 and 18, respectively.
16. The method of claim 1 , wherein the anti-LAG-3 antibody and/or anti-PD-1 antibody is a full-length antibody.
17. A kit for treating melanoma in a human patient, the kit comprising:
(a) a dose of an anti-LAG-3 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO:3, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:5;
(b) a dose of an anti-PD-1 antibody comprising CDR1, CDR2 and CDR3 domains of the heavy chain variable region having the sequence set forth in SEQ ID NO: 19, and CDR1, CDR2 and CDR3 domains of the light chain variable region having the sequence set forth in SEQ ID NO:21; and
(c) instructions for using the anti-LAG-3 antibody and anti-PD-1 antibody in the method of claim 1 .
18. The method of claim 2 , wherein the anti-CTLA-4 antibody is ipilimumab.