CTLA-4 antibody dosage escalation regimens
View Patent ↗A disease or condition, such as cancer or an infectious disease, can be treated in a patient by administering a CTLA-4 antibody in an escalating dosage regimen until a partial or complete response is elicited in the patient or a pre-determined maximum dosage is reached.
1. A method for treating a melanoma tumor in a human patient comprising administering a CTLA-4 antibody to the patient according to a dosage escalation regimen, which comprises:
(a) administering a first CTLA-4 antibody dosage of about 3 mg/kg and then administering one or more increased dosages of the CTLA-4 antibody to the patient until the dosage results in a complete response in the patient; and
(b) when the patient experiences a complete response, administering two additional cycles of the CTLA-4 antibody at the dosage level that resulted in the complete response, wherein a complete response is disappearance of the measurable melanoma tumor for greater than or equal to one month,
wherein the CTLA-4 antibody comprises a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains; and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains,
wherein the heavy chain variable region CDR1 comprises amino acids having the sequence set forth in SEQ ID NO:1; the heavy chain variable region CDR2 comprises amino acids having the sequence set forth in SEQ ID NO:2; the heavy chain variable region CDR3 comprises amino acids having the sequence set forth in SEQ ID NO:3; the light chain variable region CDR1 comprises amino acids having the sequence set forth in SEQ ID NO:4; the light chain variable region CDR2 comprises amino acids having the sequence set forth in SEQ ID NO:5; and the light chain variable region CDR3 comprises amino acids having the sequence set forth in SEQ ID NO:6.
2. The method of claim 1 , wherein the dosage escalation regimen comprises a linear increase in CTLA-4 antibody dosage.
3. The method of claim 1 , wherein the dosage escalation regimen comprises a stepwise increase in CTLA-4 antibody dosage.
4. The method of claim 1 , comprising administering a CTLA-4 dosage every three weeks.
5. The method of claim 2 , wherein the dosage escalation regimen comprises administering a first CTLA-4 antibody dosage of about 3 mg/kg, a second CTLA-4 antibody dosage of about 5 mg/kg, and a third CTLA-4 antibody dosage of about 9 mg/kg.
6. The method of claim 3 , wherein the dosage escalation regimen comprises administering an increased CTLA-4 antibody dosage every six weeks.
7. The method of claim 3 or 6 , wherein the dosage escalation regimen comprises administering a first CTLA-4 antibody dosage of about 3 mg/kg, a second CTLA-4 antibody dosage of about 3 mg/kg, a third CTLA-4 antibody dosage of about 5 mg/kg, a fourth CTLA-4 antibody dosage of about 5 mg/kg, and a fifth CTLA-4 antibody dosage of about 9 mg/kg.
8. The method of claim 1 , further comprising administering a vaccine to the patient.
9. The method of claim 8 , wherein the vaccine comprises gp100, tyrosinase, MART-1 or a combination thereof.
10. The method of claim 1 , further comprising administering a chemotherapeutic agent to the patient.
11. The method of claim 1 , further comprising administering a cytokine to the patient.
12. The method of claim 11 , wherein the cytokine is IL-2.
13. The method of claim 1 , wherein each one of the two additional cycles comprises one administration of a CTLA-4 antibody dosage.
14. The method of claim 1 , wherein the anti-CTLA-4 antibody comprises a heavy chain variable region comprising amino acids comprising the sequence set forth in SEQ ID NO:7; and a light chain variable region comprising amino acids comprising the sequence set forth in SEQ ID NO:8.
15. A method for treating a melanoma tumor in a human patient comprising administering a CTLA-4 antibody to the patient according to a dosage escalation regimen, which comprises:
(a) administering a first CTLA-4 antibody dosage of about 5 mg/kg and then administering one or more increased dosages of the CTLA-4 antibody, to the patient until the dosage results in a complete response in the patient; and
(b) when the patient experiences a complete response, administering two additional cycles of the CTLA-4 antibody at the dosage level that resulted in the complete response, wherein a complete response is disappearance of the measurable melanoma tumor for greater than or equal to one month,
wherein the CTLA-4 antibody comprises a heavy chain variable region that comprises CDR1, CDR2, and CDR3 domains; and a light chain variable region that comprises CDR1, CDR2, and CDR3 domains,
wherein the heavy chain variable region CDR1 comprises amino acids having the sequence set forth in SEQ ID NO:1; the heavy chain variable region CDR2 comprises amino acids having the sequence set forth in SEQ ID NO:2; the heavy chain variable region CDR3 comprises amino acids having the sequence set forth in SEQ ID NO:3; the light chain variable region CDR1 comprises amino acids having the sequence set forth in SEQ ID NO:4; the light chain variable region CDR2 comprises amino acids having the sequence set forth in SEQ ID NO:5; and the light chain variable region CDR3 comprises amino acids having the sequence set forth in SEQ ID NO:6.
16. The method of claim 15 , wherein the dosage escalation regimen comprises a linear increase in CTLA-4 antibody dosage.
17. The method of claim 15 , wherein the dosage escalation regimen comprises a stepwise increase in CTLA-4 antibody dosage.
18. The method of claim 15 , comprising administering a CTLA-4 antibody dosage every three weeks.
19. The method of claim 16 , wherein the dosage escalation regimen comprises administering a first CTLA-4 antibody dosage of about 5 mg/kg and a second CTLA-4 antibody dosage of about 9 mg/kg.
20. The method of claim 17 , wherein the dosage escalation regimen comprises administering an increased CTLA-4 antibody dosage every six weeks.
21. The method claim 17 or 20 , wherein the dosage escalation regimen comprises administering a first CTLA-4 antibody dosage of about 5 mg/kg, a second CTLA-4 antibody dosage of about 5 mg/kg, and a third CTLA-4 antibody dosage of about 9 mg/kg.
22. The method of claim 15 , further comprising administering a vaccine to the patient.
23. The method of claim 22 , wherein the vaccine comprises gp100, tyrosinase, MART-1 or a combination thereof.
24. The method of claim 15 , wherein each one of the two additional cycles comprises one administration of a CTLA-4 antibody dosage.
25. The method of claim 15 , wherein the anti-CTLA-4 antibody comprises a heavy chain variable region comprising amino acids comprising the sequence set forth in SEQ ID NO:7; and a light chain variable region comprising amino acids comprising the sequence set forth in SEQ ID NO:8.