Quinoxalinyl-piperazinamide methods of use
The disclosed subject matter provides methods using and kits comprising a compound of formula (I) or a pharmaceutically acceptable salt thereof.
1. A method of treating a tumor that expresses Y593 phosphorylated p68, comprising
administering to a human subject in need thereof a solid, oral dosage form comprising a compound of formula (I)
or pharmaceutically acceptable salt thereof in an amount that inhibits Y593 phosphorylated p68 activity,
wherein the solid, oral dosage form provides an AUC 0-t (0-24 hours) of about 800-15,000 hr·ng/mL after a single administration,
wherein the solid, oral dosage form is administered at a dosage of about 100-1,200 mg/day 1-7 days per week, up to about 2,800 mg/week.
2. The method of claim 1 , wherein the solid, oral dosage form is administered at a dosage of about 150-400 mg/day 3-7 days per week.
3. The method of claim 1 , wherein the solid, oral dosage form is administered at a dosage of about 150-400 mg/day 5-7 days per week.
4. The method of claim 1 , wherein the solid, oral dosage form is a tablet or capsule.
5. The method of claim 1 , wherein the solid, oral dosage form provides an AUC 0-t (0-24 hours) of about 2,500-9,500 hr·ng/mL after a single administration.
6. The method of claim 1 , wherein the solid, oral dosage form provides a C max of about 200-1,200 ng/mL after a single administration.
7. The method of claim 1 , further comprising administering radiation or an anti-tumor agent to the subject.
8. The method of claim 7 , wherein the an anti-tumor agent is selected from the group consisting of antimetabolites, DNA-fragmenting agents, DNA-crosslinking agents, intercalating agents, protein synthesis inhibitors, topoisomerase I poisons, topoisomerase II poisons, microtubule-directed agents, kinase inhibitors, polyphenols, hormones, hormone antagonists, death receptor agonists, immune checkpoint inhibitors, anti-programmed cell death 1 (PD-1) receptor antibodies and anti-programmed cell death ligand 1 (PD-L1) antibodies.
9. The method of claim 1 , further comprising administering to the subject a PD-L1 antibody or PD-1 antibody.
10. The method of claim 1 , wherein the administration inhibits β-catenin dependent ATPase activity of Y593 phosphorylated p68.
11. The method of claim 1 , further comprising:
(a) collecting a sample of the tumor from the subject before administering the solid, oral dosage form; and
(b) determining whether the tumor expresses Y593 phosphorylated p68.
12. The method of claim 1 , wherein the tumor is selected from skin cancer, prostate cancer, colon cancer, ovarian cancer, breast cancer, lymphoma, and stomach cancer.