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, 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,
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 100-500 mg/day, 1-7 days per week, up to about 2,800 mg/week, and
wherein the tumor is selected from colorectal, ovarian, lung, breast, pancreatic, and renal cancer.
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 , wherein the tumor is triple-negative (TN) breast cancer.
8. The method of claim 1 , wherein the tumor is platinum-resistant or -refractory ovarian cancer.
9. The method of claim 1 , further comprising administering radiation or an anti-tumor agent to the subject.
10. The method of claim 1 , further comprising administering to the subject an anti-tumor agent selected from 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.
11. The method of claim 1 , further comprising administering to the subject a PD-L1 antibody or PD-1 antibody.
12. A method of treating a tumor in a human subject in need thereof, comprising: (a) determining whether the subject is undergoing treatment with a CYP3A4 or CYP3A5 inhibitor or inducer; and (b) if the subject is not undergoing treatment with a CYP3A4 or CYP3A5 inhibitor or inducer, then administering to the subject a solid, oral dosage form comprising a compound of formula (I)
or pharmaceutically acceptable salt thereof,
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 100-500 mg/day, 1-7 days per week, up to about 2,800 mg/week, and
wherein the tumor is selected from colorectal, ovarian, lung, breast, pancreatic, and renal cancer.
13. The method of claim 1 , wherein the solid, oral dosage form is administered to the subject in a fed state.