Parenterally administered immune enhancing drugs
Methods of identifying compounds that modulate the conversion of AMP to adenosine by 5′-nucleotidase, ecto, and that possess particular pharmacokinetic characteristics are described herein. Methods of such compounds, and compositions comprising same, for the treatment and/or prevention of a diverse array of diseases, disorders and conditions, including cancer- and immune-related disorders, are also provided.
1. A method of treating cancer in a subject in need thereof, said method comprising administering a therapeutically effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein the compound, or a pharmaceutically acceptable salt thereof, is administered intravenously to the subject as a single dose every two weeks, three weeks, or four weeks, and wherein the therapeutically effective amount maintains a plasma concentration (Css) of at least 90 ng/mL for a period of 7 days or more.
2. The method of claim 1 , wherein said cancer is pancreatic cancer, lung cancer, colorectal cancer, prostate cancer, or is glioblastoma.
3. The method of claim 1 , further comprising administering an additional therapeutic agent.
4. The method of claim 3 , wherein the additional therapeutic agent comprises an immune checkpoint inhibitor.
5. The method of claim 4 , wherein said immune checkpoint inhibitor modulates the activity of programmed cell death protein 1 (PD1).
6. The method of claim 4 , wherein the immune checkpoint inhibitor modulates the activity of T-cell immunoreceptor with Ig and ITIM domains (TIGIT).
7. The method of claim 3 , wherein the compound, or a pharmaceutically acceptable salt thereof, and the additional therapeutic agent are administered at the same dosing frequency.
8. The method of claim 5 , further comprising administering a chemotherapeutic agent.
9. The method of claim 3 , wherein the additional therapeutic agent comprises a chemotherapeutic agent.
10. The method of claim 9 , wherein the chemotherapeutic agent is selected from gemcitabine, paclitaxel, and combinations thereof.
11. The method of claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered as a single dose every two weeks.
12. The method of claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered as a single dose every three weeks.
13. The method of claim 1 , wherein the compound, or a pharmaceutically acceptable salt thereof, is administered as a single dose every four weeks.
14. The method of claim 1 , wherein said therapeutically effective amount is between about 10 mg to about 100 mg.
15. The method of claim 1 , wherein said therapeutically effective amount is at least 25 mg.
16. The method of claim 1 , wherein the cancer is pancreatic cancer.
17. The method of claim 1 , wherein the single dose is administered intravenously over a period of 10 minutes to 1 hour.
18. The method of claim 1 , wherein the single dose is administered intravenously over a period of 30 minutes.
19. A method of treating cancer in a subject in need thereof, said method comprising administering a therapeutically effective amount of a compound having the formula:
or a pharmaceutically acceptable salt thereof, wherein the compound, or a pharmaceutically acceptable salt thereof, is administered intravenously to the subject as a single dose every two weeks, three weeks, or four weeks, and wherein said therapeutically effective amount is between about 10 mg to about 100 mg and the single dose is administered intravenously over a period of 10 minutes to 1 hour.
20. The method of claim 19 , wherein said cancer is pancreatic cancer, lung cancer, colorectal cancer, prostate cancer, or is glioblastoma.
21. The method of claim 19 , wherein the cancer is pancreatic cancer.
22. The method of claim 19 , wherein the single dose is administered intravenously over a period of 30 minutes.
23. The method of claim 19 , further comprising administering an additional therapeutic agent.
24. The method of claim 23 , wherein the additional therapeutic agent comprises a chemotherapeutic agent.
25. The method of claim 23 , wherein the additional therapeutic agent comprises an immune checkpoint inhibitor.
26. The method of claim 25 , further comprising administering a chemotherapeutic agent.
27. The method of claim 23 , wherein the additional therapeutic agent is selected from gemcitabine, paclitaxel, and combinations thereof.