Claims for Patent: 11,466,004

Summary for Patent: 11,466,004

Title:	Solid forms of an FGFR inhibitor and processes for preparing the same
Abstract:	The present disclosure relates to 3-(2,6-difluoro-3,5-dimethoxyphenyl)-1-ethyl-8-(morpholin-4-ylmethyl)-1,3,4,7-tetrahydro-2H-pyrrolo[3′,2′:5,6]pyrido[4,3-d]pyrimidin-2-one, solid forms and polymorphs thereof, methods of preparation thereof, and intermediates in the preparation thereof, which are useful in the treatment of the FGFR-associated or mediated diseases such as cancer.
Inventor(s):	Timothy C. Burn
Assignee:	Incyte Corp, Wilmington Pharmatech
Application Number:	US16/402,955
Patent Claims:	1. A method of treating cholangiocarcinoma in a patient in need thereof comprising administering to the patient a therapeutically effective amount of Compound 1 having the formula: wherein Compound 1 is administered in a daily dose of about 5 mg to about 20 mg. 2. The method of claim 1, wherein the cholangiocarcinoma is advanced or metastatic cholangiocarcinoma. 3. The method of claim 1, wherein the cholangiocarcinoma is surgically unresectable. 4. The method of claim 1, wherein the cholangiocarcinoma is intrahepatic. 5. The method of claim 1, wherein the cholangiocarcinoma is extrahepatic. 6. The method of claim 1, wherein the cholangiocarcinoma is hilar or perihilar. 7. The method of claim 1, wherein the cholangiocarcinoma is distal extrahepatic. 8. The method of claim 1, wherein the cholangiocarcinoma is characterized by FGF/FGFR genetically altered tumors. 9. The method of claim 8, wherein the tumor exhibits FGFR2 translocations. 10. The method of claim 9, wherein the FGFR2 translocation is selected from the group consisting of FGFR2-BICC1, FGFR2-AHCYL1, FGFR2-MACF1, and FGFR2 intron 17 rearrangement. 11. The method of claim 8, wherein the tumor exhibits FGF/FGFR alterations other than FGFR2 translocations. 12. The method of claim 1, wherein the cholangiocarcinoma does not exhibit FGF/FGFR genetically altered tumors. 13. The method of claim 1, wherein the patient has failed at least one previous treatment. 14. The method of claim 13, wherein the previous treatment is surgery or radiation therapy. 15. The method of claim 1, wherein the patient has a history of hepatitis. 16. The method of claim 15, wherein the hepatitis is chronic hepatitis B or hepatitis C. 17. The method of claim 1, wherein Compound 1 is administered in a daily dose of about 10 mg to about 15 mg. 18. The method of claim 1, wherein Compound 1 is administered in a daily dose of about 13.5 mg. 19. The method of claim 1, wherein Compound 1 is administered as a tablet. 20. The method of claim 1, wherein Compound 1 is administered in a daily dose of about 9 mg. 21. A method of treating cholangiocarcinoma in a patient in need thereof comprising administering to the patient a therapeutically effective amount of Compound 1 having the formula: wherein Compound 1 is administered once daily as a tablet, and wherein the tablet comprises about 0.5 to about 10 mg of Compound 1. 22. The method of claim 21, wherein the tablet comprises about 0.5 mg to about 5 mg of Compound 1. 23. The method of claim 21, wherein the tablet comprises about 9 mg of Compound 1. 24. The method of claim 21, wherein the tablet comprises about 4.5 mg of Compound 1. 25. The method of claim 21, wherein the cholangiocarcinoma is advanced or metastatic cholangiocarcinoma. 26. The method of claim 21, wherein the cholangiocarcinoma is surgically unresectable. 27. The method of claim 21, wherein the cholangiocarcinoma is intrahepatic. 28. The method of claim 21, wherein the cholangiocarcinoma is extrahepatic. 29. The method of claim 21, wherein the cholangiocarcinoma is hilar or perihilar. 30. The method of claim 21, wherein the cholangiocarcinoma is distal extrahepatic. 31. The method of claim 21, wherein the cholangiocarcinoma is characterized by FGF/FGFR genetically altered tumors. 32. The method of claim 31, wherein the tumor exhibits FGFR2 translocations. 33. The method of claim 32, wherein the FGFR2 translocation is selected from the group consisting of FGFR2-BICC1, FGFR2-AHCYL1, FGFR2-MACF1, and FGFR2 intron 17 rearrangement. 34. The method of claim 31, wherein the tumor exhibits FGF/FGFR alterations other than FGFR2 translocations. 35. The method of claim 21, wherein the cholangiocarcinoma does not exhibit FGF/FGFR genetically altered tumors. 36. The method of claim 21, wherein the patient has failed at least one previous treatment. 37. The method of claim 36, wherein the previous treatment is surgery or radiation therapy. 38. A method of treating cholangiocarcinoma in a patient in need thereof comprising administering to the patient a therapeutically effective amount of Compound 1 having the formula: wherein Compound 1 is administered in a 21-day dosing regimen, wherein the 21-day dosing regimen comprises: (a) a first period wherein Compound 1 is administered once daily for 14 days; and (b) a second period wherein Compound 1 is not administered for 7 days. 39. The method of claim 38, wherein Compound 1 is administered in a daily dose of about 5 mg to about 20 mg during the first period. 40. The method of claim 38, wherein Compound 1 is administered in a daily dose of about 10 mg to about 15 mg during the first period. 41. The method of claim 38, wherein Compound 1 is administered in a daily dose of about 13.5 mg during the first period. 42. The method of claim 38, wherein Compound 1 is administered in a daily dose of about 9 mg during the first period. 43. The method of claim 38, wherein Compound 1 is administered as a tablet during the first period. 44. The method of claim 43, wherein the tablet comprises about 0.5 mg to about 10 mg of Compound 1. 45. The method of claim 43, wherein the tablet comprises about 0.5 mg to about 5 mg of Compound 1. 46. The method of claim 43, wherein the tablet comprises about 9 mg of Compound 1. 47. The method of claim 43, wherein the tablet comprises about 4.5 mg of Compound 1. 48. The method of claim 38, wherein the cholangiocarcinoma is advanced or metastatic cholangiocarcinoma. 49. The method of claim 38, wherein the cholangiocarcinoma is surgically unresectable. 50. The method of claim 38, wherein the cholangiocarcinoma is intrahepatic. 51. The method of claim 38, wherein the cholangiocarcinoma is extrahepatic. 52. The method of claim 38, wherein the cholangiocarcinoma is hilar or perihilar. 53. The method of claim 38, wherein the cholangiocarcinoma is distal extrahepatic. 54. The method of claim 38, wherein the cholangiocarcinoma is characterized by FGF/FGFR genetically altered tumors. 55. The method of claim 54, wherein the tumor exhibits FGFR2 translocations. 56. The method of claim 55, wherein the FGFR2 translocation is selected from the group consisting of FGFR2-BICC1, FGFR2-AHCYL1, FGFR2-MACF1, and FGFR2 intron 17 rearrangement. 57. The method of claim 54, wherein the tumor exhibits FGF/FGFR alterations other than FGFR2 translocations. 58. The method of claim 38, wherein the cholangiocarcinoma does not exhibit FGF/FGFR genetically altered tumors. 59. The method of claim 38, wherein the patient has failed at least one previous treatment. 60. The method of claim 59, wherein the previous treatment is surgery or radiation therapy.