METHODS OF TREATMENT WITH ANTAGONISTS AGAINST PD-1 AND PD-L1 IN COMBINATION WITH RADIATION THERAPY

• US 20160051672A1
• Filed: 06/16/2015
• Published: 02/25/2016
• Est. Priority Date: 06/17/2014
• Status: Active Grant

• Current Assignee: MedImmune Ltd. (Astrazeneca PLC)
• Original Assignee: MedImmune Ltd. (Astrazeneca PLC), University of Manchester
• Inventors: Morrow, Michelle, STEWART, Ross, Wilkinson, Robert, Poon, Edmund, Dovedi, Simon, Illidge, Tim
• Granted Patent: US 10,092,645 B2
• Time in Patent Office: Days
• US Class Current: 1/1
• CPC Class Codes: A61K 2039/505 comprising antibodies
• 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 39/3955 against proteinaceous materials, e.g. enzymes, hormones, lymphokines
• CPC Class Codes: A61K 39/39558 against tumor tissues, cells, antigens
• CPC Class Codes: A61N 5/10 X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy A61N5/01 takes precedence
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 35/02 specific for leukemia
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07K 16/2818 against CD28 or CD152
• CPC Class Codes: C07K 16/2827 against B7 molecules, e.g. CD80, CD86
• CPC Class Codes: C07K 2317/73 Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation

Abstract

This application provides a method of treating cancer in a patient comprising administering at least one dose of radiation therapy and at least one PD-1 and/or PD-L1 antagonist, wherein at least one PD-1 and/or PD-L1 antagonist is administered on the same day as a dose of radiation therapy or up to and including 4 days later.

Claims

1. A method of treating cancer in a patient comprising

a. administering at least one dose of radiation therapy;

and

b. administering at least one PD-1 and/or PD-L1 antagonist,

wherein at least one PD-1 and/or PD-L1 antagonist is administered on the same day as a dose of radiation therapy or up to and including 4 days later.

2. The method of claim 1, wherein the at least one PD-1 and/or PD-L1 antagonist is an at least one PD-1 and/or PD-L1 antibody or functional part thereof.

3. The method of claim 1, wherein the dose of radiation therapy is about 70 Gy or lower.

4. The method of claim 3, wherein the dose of radiation therapy is about 50 Gy or lower.

5. The method of claim 4, wherein the radiation therapy is fractionated radiation therapy.

6. The method of claim 5, wherein the fractionated radiation therapy comprises from 2 to 7 fractions.

7. The method of claim 6, wherein the fractionated radiation therapy comprises 5 fractions.

8. The method of claim 7, wherein the radiation therapy fractions are administered in sequential days.

9. The method of claim 8, wherein the radiation therapy fractions are administered on day 1, day 2, day 3, day 4, and day 5.

10. The method of claim 9, wherein the radiation therapy comprises about 70 Gy in 5 fractions.

11. The method of claim 1, wherein the at least one PD-1 and/or PD-L1 antagonist is administered on day 1.

12. The method of claim 1, wherein the at least one PD-1 and/or PD-L1 antagonist is administered on day 5.

13. The method of claim 1, wherein the at least one PD-1 and/or PD-L1 antagonist is administered multiple times.

14. The method of claim 13, wherein the at least one PD-1 and/or PD-L1 antagonist is administered 3 times a week.

15. The method of claim 14, wherein the anti-PD-1 and/or PD-L1 antibody or functional part thereof is MEDI4736.

16. The method of claim 15, wherein the anti-PD-1 and/or anti-PD-L1 antibody or functional part thereof is pembrolizumab, nivolumab, BMS-936558, AMP-224, or MPDL3280A.

17. The method of claim 1, wherein the cancer is melanoma, colorectal cancer, or breast cancer.

18. The method of claim 1, wherein more than one treatment cycle is performed.

19. The method of claim 18, wherein from 2-8 treatment cycles are performed.

20. The method of claim 19, wherein the treatment cycles are weekly or every other week.