Co-crystals, pharmaceutical compositions based on them and methods of treatment involving their use

Abstract

Solid forms of the compound useful for treating cancer, pharmaceutical compositions based on them, and methods for treating cancer, including administering to a patient in need thereof, the solid forms described herein are provided.

Claims

1. The crystalline form of the compound of formula (I) the powder X-ray diffraction pattern of which comprises peaks at the following positions, expressed in degrees of angle 2-theta (±0.2 degrees of angle 2-theta): 11.7, 17.8 and 21.8, and at least three peaks at positions selected from the group consisting of 12.8, 14.2, 19.8, 20.7, 22.2 and 25.

0.

2. The crystalline form of claim 1, the powder X-ray diffraction pattern of which contains peaks at the following positions, expressed in degrees 2-theta (±0.2 degrees 2-theta): 11.7, 12.8, 14.2, 17.8, 19.8, 20.7, 21.8, 22.2 and 25.

0.

3. The crystalline form according to claim 1 or 2, wherein the crystalline form is characterized by a differential scanning calorimetry thermogram containing an endothermic peak characterized by a phase transition onset temperature of 221.9°C (±5.0°C).

4. A pharmaceutical composition comprising a therapeutically effective amount of the crystalline form according to claim 1 and one or more pharmaceutical excipients.

5. A method for treating cancer characterized by the presence of an IDH1 or IDH2 mutation in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the crystalline form according to any one of claims 1-3 or the pharmaceutical composition according to claim 4.

6. The method according to claim 5, wherein the cancer is characterized by the presence of an IDH1 mutation.

7. The method of claim 6, wherein the IDH1 mutation is the R132X mutation.

8. The method according to claim 6, wherein the IDH1 mutation is an R132H or R132C mutation.

9. The method according to claim 5, wherein the cancer is characterized by the presence of an IDH2 mutation.

10. The method according to claim 9, wherein the IDH2 mutation is the R140X mutation.

11. The method according to claim 9, wherein the IDH2 mutation is an R140Q, R140W or R140L mutation.

12. The method according to claim 9, wherein the IDH2 mutation is the R172X mutation.

13. The method according to claim 9, wherein the IDH2 mutation is an R172K or R172G mutation.

14. The method according to any one of claims 5-13, wherein the cancer is selected from glioma, acute myelogenous leukemia, sarcoma, melanoma, non-small cell lung cancer (NSCLC), types of cholangiocarcinoma, chondrosarcoma, myelodysplastic syndromes (MDS), myeloproliferative neoplasm (MPN), colon cancer and angioimmunoblastic non-Hodgkin's lymphoma (NHL).

15. The method according to claim 14, wherein the cancer is a glioma.

16. The method according to claim 15, wherein the glioma is a low-grade glioma or a secondary high-grade glioma.

17. The method according to claim 15, wherein the glioma is a low-grade glioma.

18. The method according to claim 15, wherein the glioma is a secondary high-grade glioma and wherein the secondary high-grade glioma is a glioblastoma.

19. The method according to any one of claims 5-18, wherein the cancer is refractory or recurrent.

20. The method according to any one of claims 5 to 18, wherein the cancer is a newly diagnosed cancer or a cancer that has not been previously treated.

21. The method according to any one of paragraphs 5-20, wherein the method further comprises administering to the patient an additional therapeutic agent.

22. The method according to any one of claims 5 to 21, wherein the patient has previously been administered an anti-cancer therapy for the treatment of cancer.

23. The method according to any one of claims 5 to 22, comprising administering to the patient a daily dose of about 10 mg, about 25 mg, about 50 mg, about 100 mg, about 200 mg or about 300 mg of the compound of formula (I) in crystalline form or as part of a pharmaceutical composition.

24. The method according to any one of claims 5 to 22, comprising administering to the patient a dose of about 10 mg or about 50 mg twice a day of a compound of formula (I) in crystalline form or as part of a pharmaceutical composition.

Images