Crystalline forms of an azetidine parp1 inhibitor

Abstract

Described herein are crystalline forms of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1), or a pharmaceutically acceptable salt or solvate thereof. Compound 1.

Description

Abstract This paper describes the crystalline form of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5-naphthidin-3-yl)methyl)-2-methylazacyclobutane-3-yl)oxy)-N-cyclopropylpyridine amide (Compound 1) or its pharmaceutically acceptable salts or solvates. Compound 1.

Claims

Attorney Docket No.: 37D-350681-WO XIN729-WO CLAIMS We Claim:

1. A crystalline form of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5-naphthyridin-3-yl)methyl)- 2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable salt or solvate2. A crystalline form of freebase 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5-naphthyridin-3- yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1):

3. The crystalline form of claim 2, wherein the solvate is a hydrate.

4. A crystalline form of anhydrous freebase 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): .

5. A crystalline form of the maleate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1):

6. The crystalline form of claim 5, wherein the solvate is a hydrate.Attorney Docket No.: 37D-350681-WO XIN729-WO 7. A crystalline form of the anhydrous maleate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro- 1,5-naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): .

8. -1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate9. The crystalline form of claim 8, wherein the solvate is a hydrate.

10. A crystalline form of the anhydrous tartrate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro- 1,5-naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): .

11. The crystalline form of any one of claims 1-9, wherein the crystalline form is selected from the group consisting of freebase Form I of Compound 1, freebase Form II of Compound 1, Maleate Salt Form IV of Compound 1, and Tartrate Salt Form I of Compound 1, or any combinations thereof.

12. The crystalline form of any one of claims 1-2, wherein the crystalline Compound 1 is freebase Form I characterized as having at least one of the following properties: (a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1A; (b) an X-ray powder diffraction (XRPD) pattern with a characteristic peak at 20.50 ± 0.1° 2θ; (c) a DSC thermogram with an endotherm having a peak temperature at about 228 °C (onset); (d) a DSC thermogram with an exotherm having a peak temperature at about 231 °C (onset);Attorney Docket No.: 37D-350681-WO XIN729-WO (e) a DSC thermogram with an endotherm having a peak temperature at about 238 °C (onset); or (f) combinations thereof.

13. The crystalline form of any one of claims 1-2, wherein the crystalline Compound 1 is freebase Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 8.4, 12.6, and 20.7 °2θ as determined on a diffractometer using Cu-Kα radiation..

14. The crystalline form of claim 13, further characterized by (a) one or more additional peaks (± 0.2°) at 17.7, 23.7, or 27.5 °2θ; (b) one or more additional peaks (± 0.2°) at 21.4, 24.6, or 28.7 °2θ; (c) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 1B; (c) a DSC thermogram comprising an endothermic onset at about 223 °C, an exothermic onset at about 227 °C, and an endothermic onset at about 237 °C; (d) a DSC thermogram substantially the same as shown in FIG.1C; (e) thermogravimetric analysis (TGA) showing a weight loss of about 0.1% from about 25- 157 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.1D; or (g) combinations thereof.

15. The crystalline form of any one of claims 1-2, wherein the crystalline freebase Compound 1 is Form II characterized as having at least one of the following properties: (a) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 2A; (b) an X-ray powder diffraction (XRPD) pattern with a characteristic peak at 13.39 ± 0.1° 2θ; (c) a DSC thermogram with an endotherm having a peak temperature at about 235 °C (onset); or (d) combinations thereof.

16. The crystalline form of any one of claims 1-2, wherein the crystalline Compound 1 is freebase Form III characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 16.8, 21.4, and 26.2 °2θ as determined on a diffractometer using Cu-Kα radiation.

17. The crystalline form of claim 16, further characterized by:Attorney Docket No.: 37D-350681-WO XIN729-WO (a) one or more additional peaks (± 0.2°) at 7.6, 17.5, or 22.8 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.3; (c) a DSC thermogram comprising an endothermic onset at about 193 °C, an exothermic onset at about 204 °C, and an endothermic onset at about 231 °C; (d) a DSC thermogram substantially the same as shown in FIG.4; (e) thermogravimetric analysis (TGA) showing a weight loss of about 1.2% from about 25- 100 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.5; or (g) combinations thereof.

18. A crystalline form of the sulfate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate19. The crystalline form of claim 18, wherein the crystalline Compound 1 is Sulfate Salt Form III characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 23.4, 24.0, and 28.8 °2θ as determined on a diffractometer using Cu-Kα radiation.

20. The crystalline form of claim 19, further characterized by: (a) one or more additional peaks (± 0.2°) at 19.1, 19.7, or 24.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.6; (c) a DSC thermogram comprising an endothermic onset at about 34 °C and an endothermic onset at about 163 °C; (d) a DSC thermogram substantially the same as shown in FIG.7; (e) thermogravimetric analysis (TGA) showing a weight loss of about 6.6% from about 25- 150 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.8; (g) a dynamic vapor sorption (DVS) curve showing about 6% water uptake from 0 to 90% relative humidity (RH) at 25 °C; (h) a dynamic vapor sorption (DVS) curve substantially as shown in FIG.9 or (i) combinations thereof.Attorney Docket No.: 37D-350681-WO XIN729-WO 21. A crystalline form of the esylate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate22. The crystalline form of claim 21, wherein the crystalline Compound 1 is Esylate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 17.5, 25.5, and 26.9 °2θ as determined on a diffractometer using Cu-Kα radiation.

23. The crystalline form of claim 22, further characterized by: (a) one or more additional peaks (± 0.2°) at 13.2, 15.8, or 21.6 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.10; (c) a DSC thermogram comprising an endothermic onset at about 58 °C and an endothermic onset at about 140 °C; (d) a DSC thermogram substantially the same as shown in FIG.11; (e) thermogravimetric analysis (TGA) showing a weight loss of about 12.5% from about 25- 100 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.12; or (g) combinations thereof.

24. A crystalline form of the tosylate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate25. The crystalline form of claim 24, wherein the crystalline Compound 1 is Tosylate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 12.3, 14.9, and 19.7 °2θ as determined on a diffractometer using Cu-Kα radiation.

26. The crystalline form of claim 25, further characterized by:Attorney Docket No.: 37D-350681-WO XIN729-WO (a) one or more additional peaks (± 0.2°) at 16.8, 22.1, or 29.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.13; or (c) a combination thereof.

27. A crystalline form of the hemiedisylate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate28. The crystalline form of claim 27, wherein the crystalline Compound 1 is Hemiedisylate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 12.9, 26.5, and 27.7 °2θ as determined on a diffractometer using Cu-Kα radiation.

29. The crystalline form of claim 28, further characterized by: (a) one or more additional peaks (± 0.2°) at 16.3, 18.0, or 26.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.14; or (c) a combination thereof.

30. The crystalline form of claim 27, wherein the crystalline Compound 1 is Hemiedisylate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 16.4, 21.2, and 27.8 °2θ as determined on a diffractometer using Cu-Kα radiation.

31. The crystalline form of claim 30, further characterized by: (a) one or more additional peaks (± 0.2°) at 11.4, 17.9, or 25.6 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.15; (c) a DSC thermogram comprising an endothermic onset at about 96 °C and an endothermic onset at about 194 °C; (d) a DSC thermogram substantially the same as shown in FIG.16; (e) thermogravimetric analysis (TGA) showing a weight loss of about 1.7% from about 25- 87 °C and a weight loss of about 2.8% from about 87-120 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.17;Attorney Docket No.: 37D-350681-WO XIN729-WO (g) a dynamic vapor sorption (DVS) curve showing about 3.6% water uptake from 0 to 90% RH at 25 °C; (h) a dynamic vapor sorption (DVS) curve substantially as shown in FIG.18; or (i) combinations thereof.

32. A crystalline form of the phosphate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate33. The crystalline form of claim 32, wherein the crystalline Compound 1 is Phosphate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 12.8, 25.7, and 26.9 °2θ as determined on a diffractometer using Cu-Kα radiation.

34. The crystalline form of claim 33, further characterized by: (a) one or more additional peaks (± 0.2°) at 15.1, 17.3, or 21.5 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.19; (c) a DSC thermogram comprising an endothermic onset at about 28 °C and an endothermic onset at about 133 °C; (d) a DSC thermogram substantially the same as shown in FIG.20; or (e) combinations thereof.

35. The crystalline form of claim 32, wherein the crystalline Compound 1 is Phosphate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 4.7, 16.0, and 17.2 °2θ as determined on a diffractometer using Cu-Kα radiation.

36. The crystalline form of claim 35, further characterized by: (a) one or more additional peaks (± 0.2°) at 5.7, 6.8, or 9.4 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.21; (c) a DSC thermogram comprising an endothermic onset at about 21 °C and an endothermic onset at about 142 °C; (d) a DSC thermogram substantially the same as shown in FIG.22; or (e) combinations thereof.Attorney Docket No.: 37D-350681-WO XIN729-WO 37. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Mesophase characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 17.5, 24.1, and 25.4 °2θ as determined on a diffractometer using Cu-Kα radiation.

38. The crystalline form of claim 37, further characterized by: (a) one or more additional peaks (± 0.2°) at 4.4, 8.8, or 13.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.23; or (c) a combination thereof.

39. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 7.5, 14.9, and 15.8 °2θ as determined on a diffractometer using Cu-Kα radiation.

40. The crystalline form of claim 39, further characterized by: (a) one or more additional peaks (± 0.2°) at 21.3, 22.5, or 23.0 °2θ; (b) one or more additional peaks (± 0.2°) at 6.3, 24.1, or 28.2 °2θ; (c) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 43A; (d) a DSC thermogram comprising an endothermic onset at about 113 °C; (e) a DSC thermogram substantially the same as shown in FIG.44; (f) thermogravimetric analysis (TGA) showing a weight loss of about 6.1% from about 25- 130 °C; (g) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.45; (h) a dynamic vapor sorption (DVS) curve showing about 1.1% water uptake from 0 to 90% relative humidity (RH) at 25 °C; (i) a dynamic vapor sorption (DVS) curve substantially as shown in FIG.46; or (j) combinations thereof.

41. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 9.4, 15.7, and 18.4 °2θ as determined on a diffractometer using Cu-Kα radiation.

42. The crystalline form of claim 41, further characterized by: (a) one or more additional peaks (± 0.2°) at 9.1, 20.4, or 32.1 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.24;Attorney Docket No.: 37D-350681-WO XIN729-WO (c) a DSC thermogram comprising an endothermic onset at about 49 °C, an endothermic onset at about 91 °C, and an endothermic onset at about 119 °C; (d) a DSC thermogram substantially the same as shown in FIG.25; (e) thermogravimetric analysis (TGA) showing a weight loss of about 8% from about 25-70 °C and a weight loss of about 1.6% from about 70-100 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.26; (g) a dynamic vapor sorption (DVS) curve showing about 10.2% water uptake from 0 to 90% RH at 25 °C; (h) a dynamic vapor sorption (DVS) curve substantially as shown in FIG.27; or (i) combinations thereof.

43. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Form III characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 4.7, 9.4, and 14.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

44. The crystalline form of claim 43, further characterized by: (a) one or more additional peaks (± 0.2°) at 16.8, 17.4, or 18.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.28; (c) a DSC thermogram comprising an endothermic onset at about 174 °C; (d) a DSC thermogram substantially the same as shown in FIG.29; (e) thermogravimetric analysis (TGA) showing a weight loss of about 2% from about 25-70 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.30; or (g) combinations thereof.

45. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Form IV characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 15.8, 16.6, and 22.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

46. The crystalline form of claim 45, further characterized by: (a) one or more additional peaks (± 0.2°) at 6.5, 12.9, or 20.4 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.31; (c) a DSC thermogram comprising an endothermic onset at about 79 °C and an endothermic onset at about 127 °C; (d) a DSC thermogram substantially the same as shown in FIG.32;Attorney Docket No.: 37D-350681-WO XIN729-WO (e) thermogravimetric analysis (TGA) showing a weight loss of about 5% from about 25- 125 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.33; or (g) combinations thereof.

47. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Methanol solvate characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 8.7, 16.7, and 17.4 °2θ as determined on a diffractometer using Cu-Kα radiation.

48. The crystalline form of claim 47, further characterized by: (a) one or more additional peaks (± 0.2°) at 9.4, 18.9, or 21.0 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.34; or (c) a combination thereof.

49. The crystalline form of claim 8, wherein the crystalline Compound 1 is L-Tartrate Salt Ethanol solvate characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 8.7, 17.3, and 19.4 °2θ as determined on a diffractometer using Cu-Kα radiation.

50. The crystalline form of claim 49, further characterized by: (a) one or more additional peaks (± 0.2°) at 4.4, 21.7, or 24.6 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.35; or (c) a combination thereof.

51. A crystalline form of the L-malate salt of 5-(((2R,3S)-1-((7-chloro-6-oxo-5,6-dihydro-1,5- naphthyridin-3-yl)methyl)-2-methylazetidin-3-yl)oxy)-N-cyclopropylpicolinamide (Compound 1): a pharmaceutically acceptable solvate thereof.

52. The crystalline form of claim 51, wherein the crystalline Compound 1 is L-Malate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 16.3, 21.5, and 24.8 °2θ as determined on a diffractometer using Cu-Kα radiation.Attorney Docket No.: 37D-350681-WO XIN729-WO 53. The crystalline form of claim 52, further characterized by: (a) one or more additional peaks (± 0.2°) at 14.7, 23.8, and 27.7 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.36; (c) a DSC thermogram comprising an endothermic onset at about 165 °C; (d) a DSC thermogram substantially the same as shown in FIG.37; (e) thermogravimetric analysis (TGA) showing a weight loss of about 1.8% from about 25- 100 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.38; (g) a dynamic vapor sorption (DVS) curve showing about 4.6% water uptake from 0 to 90% RH at 25 °C; (h) a dynamic vapor sorption (DVS) curve substantially as shown in FIG.39; or (i) combinations thereof.

54. The crystalline form of claim 51, wherein the crystalline Compound 1 is L-Malate Salt Form III characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 17.1, 17.9, and 26.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

55. The crystalline form of claim 54, further characterized by: (a) one or more additional peaks (± 0.2°) at 8.8, 24.2, or 28.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG.40; (c) a DSC thermogram comprising an endothermic onset at about 120 °C and an endothermic onset at about 153 °C; (d) a DSC thermogram substantially the same as shown in FIG.41; (e) thermogravimetric analysis (TGA) showing a weight loss of about 0.7% from about 25- 50 °C; (f) thermogravimetric analysis (TGA) comprising a thermogram substantially as shown in FIG.42; or (g) combinations thereof.

56. The crystalline form of claim 5, wherein the crystalline Compound 1 is Maleate Salt Form IV characterized as having at least one of the following properties: (a) an X-ray powder diffraction (XRPD) pattern with characteristic peaks at 3.93 ± 0.1° 2θ, 19.60 ± 0.1° 2θ, and 22.55 ± 0.1° 2θ; (b) a DSC thermogram with an endotherm having a peak temperature at about 183 °C (onset); or (c) combinations thereof.Attorney Docket No.: 37D-350681-WO XIN729-WO 57. The crystalline form of claim 1, wherein the crystalline Compound 1 is HCl Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 7.2, 12.2, and 14.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

58. The crystalline form of claim 57, further characterized by: (a) one or more additional peaks (± 0.2°) at 15.3, 25.2, 27.1, 27.7, 28.0, and 29.9°2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 50A; (c) a DSC thermogram comprising an endothermic onset at about 216 °C; (d) a DSC thermogram substantially the same as shown in FIG.50B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 2.2% from about 25- 200 °C; (f) TGA comprising a thermogram substantially as shown in FIG.50B; or (g) combinations thereof.

59. The crystalline form of claim 1, wherein the crystalline Compound 1 is HCl Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 5.0, 9.9, and 17.6 °2θ as determined on a diffractometer using Cu-Kα radiation.

60. The crystalline form of claim 59, further characterized by: (a) one or more additional peaks (± 0.2°) at 9.0, 12.7, 18.8, 24.9, 25.4, 26.5, and 27.0 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 51A; (c) a DSC thermogram comprising an endothermic onset at about 115 °C and an endothermic onset at about 147 °C; (d) a DSC thermogram substantially the same as shown in FIG.51B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 6.8% from about 25- 165 °C; (f) TGA comprising a thermogram substantially as shown in FIG.51B; or (g) combinations thereof.

61. The crystalline form of claim 18, wherein the crystalline Compound 1 is Sulfate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 7.3, 17.4, and 18.9 °2θ as determined on a diffractometer using Cu-Kα radiation.

62. The crystalline form of claim 61, further characterized by: (a) one or more additional peaks (± 0.2°) at 4.8, 10.1, 16.7, 19.2, 25.2, and 25.9 °2θ;Attorney Docket No.: 37D-350681-WO XIN729-WO (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 52A; (c) a DSC thermogram comprising an endothermic onset at about 52 °C, an endothermic onset at about 99 °C, and an endothermic onset at about 152 °C; (d) a DSC thermogram substantially the same as shown in FIG.52B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 5.3% from about 25- 170 °C; (f) TGA comprising a thermogram substantially as shown in FIG.52B; or (g) combinations thereof.

63. The crystalline form of claim 18, wherein the crystalline Compound 1 is Sulfate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 6.2, 18.5, and 24.7 °2θ as determined on a diffractometer using Cu-Kα radiation.

64. The crystalline form of claim 63, further characterized by (a) one or more additional peaks (± 0.2°) at 10.4, 12.0, 16.0, 21.8, and 31.1°2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 53A; (c) a DSC thermogram comprising an endothermic onset at about 223 °C; (d) a DSC thermogram substantially the same as shown in FIG.53B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 1.5% from about 25- 150 °C; (f) TGA comprising a thermogram substantially as shown in FIG.53C; or (g) combinations thereof.

65. The crystalline form of claim 1, wherein the crystalline Compound 1 is Maleate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 3.9, 19.6, and 20.9 °2θ as determined on a diffractometer using Cu-Kα radiation.

66. The crystalline form of claim 65, further characterized by: (a) one or more additional peaks (± 0.2°) at 15.6, 17.4, 20.7, 24.6, 28.3, and 29.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 54A; (c) a DSC thermogram comprising an endothermic onset at about 177 °C; (d) a DSC thermogram substantially the same as shown in FIG.54B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 1.0% from about 25- 70 °C and a weight loss of about 3.7% from about 150-200 °C;Attorney Docket No.: 37D-350681-WO XIN729-WO (f) TGA comprising a thermogram substantially as shown in FIG.54B; or (g) combinations thereof.

67. The crystalline form of claim 1, wherein the crystalline Compound 1 is Maleate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 3.6, 18.1, and 22.9 °2θ as determined on a diffractometer using Cu-Kα radiation.

68. The crystalline form of claim 67, further characterized by: (a) one or more additional peaks (± 0.2°) at 7.2, 9.7, 10.8, 16.0, and 18.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 55A; (c) a DSC thermogram comprising an endothermic onset at about 131 °C and an endothermic onset at about 177 °C; (d) a DSC thermogram substantially the same as shown in FIG.55B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 3.3% from about 120-160 °C and a weight loss of about 5.4% from about 160-210 °C; (f) TGA comprising a thermogram substantially as shown in FIG.55B; or (g) combinations thereof.

69. The crystalline form of claim 1, wherein the crystalline Compound 1 is Maleate Salt Form III characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 9.0, 17.9, and 25.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

70. The crystalline form of claim 69, further characterized by: (a) one or more additional peaks (± 0.2°) 12.1, 15.2, 19.0, 19.6, 24.7, and 28.1 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 56C; or (c) combinations thereof.

71. The crystalline form of claim 1, wherein the crystalline Compound 1 is Citrate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 9.9, 15.5, and 16.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

72. The crystalline form of claim 71, further characterized by: (a) one or more additional peaks (± 0.2°) at 12.8, 17.1, 19.2, 19.8, 23.6, and 24.5 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 57A;Attorney Docket No.: 37D-350681-WO XIN729-WO € a DSC thermogram comprising an endothermic onset at about 27 °C and an endothermic onset at about 177 °C; (d) a DSC thermogram substantially the same as shown in FIG.57B; € thermogravimetric analysis (TGA) showing a weight loss of about 2.3% from about 25- 100 °C and a weight loss of about 12% from about 150-210 °C; (f) TGA comprising a thermogram substantially as shown in FIG.57B; or (g) combinations thereof.

73. The crystalline form of claim 1, wherein the crystalline Compound 1 is L-Malate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 8.9, 11.9, and 17.8 °2θ as determined on a diffractometer using Cu-Kα radiation.

74. The crystalline form of claim 73, further characterized by: (a) one or more additional peaks (± 0.2°) at 9.8, 12.6, 15.0, 18.8, 19.4, and 25.1 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 58A; (c) a DSC thermogram comprising an endothermic onset at about 29 °C, an endothermic onset at about 161 °C, and an endothermic onset at about 180 °C; (d) a DSC thermogram substantially the same as shown in FIG.58B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 2.9% from about 25- 110 °C and a weight loss of about 1.5% from about 150-210 °C; (f) TGA comprising a thermogram substantially as shown in FIG.58B; or (g) combinations thereof.

75. The crystalline form of claim 1, wherein the crystalline Compound 1 is Mesylate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 6.5, 15.2, and 25.3 °2θ as determined on a diffractometer using Cu-Kα radiation.

76. The crystalline form of claim 75, further characterized by: (a) one or more additional peaks (± 0.2°) at 10.0, 16.6, 17.5, 18.5, 19.7, and 26.2 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 59A; (c) a DSC thermogram comprising an endothermic onset at about 37 °C and an endothermic onset at about 148 °C; (d) a DSC thermogram substantially the same as shown in FIG.59B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 6.1% from about 25- 100 °C;Attorney Docket No.: 37D-350681-WO XIN729-WO (f) TGA comprising a thermogram substantially as shown in FIG.59B; or (g) combinations thereof.

77. The crystalline form of claim 1, wherein the crystalline Compound 1 is Mesylate Salt Form II characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 10.7, 13.0, and 17.1 °2θ as determined on a diffractometer using Cu-Kα radiation.

78. The crystalline form of claim 77, further characterized by: (a) one or more additional peaks (± 0.2°) at 6.5, 8.5, 15.4, 19.7, 21.9, and 25.3 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 60A; (c) a DSC thermogram comprising an endothermic onset at about 37 °C and an endothermic onset at about 149 °C; (d) a DSC thermogram substantially the same as shown in FIG.60B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 4.7% from about 25- 120 °C and a weight loss of about 0.7% from about 120-170 °C; (f) TGA comprising a thermogram substantially as shown in FIG.60B; or (g) combinations thereof.

79. The crystalline form of claim 1, wherein the crystalline Compound 1 is Tosylate Salt Form I characterized by an X-ray power diffractogram comprising peaks (± 0.2°) at 24.0, 24.6, and 25.6 °2θ as determined on a diffractometer using Cu-Kα radiation.

80. The crystalline form of claim 79, further characterized by: (a) one or more additional peaks (± 0.2°) at 5.2, 8.0, 17.7, 11.8, 23.7, and 27.9 °2θ; (b) an X-ray powder diffraction (XRPD) pattern substantially the same as shown in FIG. 61A; (c) a DSC thermogram comprising an endothermic onset at about 82 °C and an endothermic onset at about 142 °C; (d) a DSC thermogram substantially the same as shown in FIG.61B; (e) thermogravimetric analysis (TGA) showing a weight loss of about 2.6% from about 25- 170 °C; (f) TGA comprising a thermogram substantially as shown in FIG.61B; or (g) combinations thereof.

81. The crystalline form of claim 1, wherein the crystalline form is selected from the group consisting of freebase Form I of Compound 1, freebase Form II of Compound 1, freebase Form III ofAttorney Docket No.: 37D-350681-WO XIN729-WO Compound 1, Maleate Salt Form IV of Compound 1, Tartrate Salt Form I of Compound 1, Sulfate Salt Form III of Compound 1, Esylate Salt Form I of Compound 1, Tosylate Salt Form II of Compound 1, Hemiedisylate Salt Form I of Compound 1, Hemiedisylate Salt Form II of Compound 1, Phosphate Salt Form I of Compound 1, Phosphate Salt Form II of Compound 1, L-Tartrate Mesophase of Compound 1, L-Tartrate Salt Form II of Compound 1, L-Tartrate Salt Form III of Compound 1, L-Tartrate Salt Form IV of Compound 1, L-Tartrate Salt Methanol solvate of Compound 1, L-Tartrate Salt Ethanol solvate of Compound 1, L-malate Salt Form II of Compound 1, L-malate Salt Form III of Compound 1, HCl salt Form I of Compound 1, HCl Salt Form II of Compound 1, Sulfate Salt Form I of Compound 1, Sulfate Salt Form II of Compound 1, Maleate Salt Form I of Compound 1, Maleate Salt Form II of Compound 1, Maleate Salt Form III of Compound 1, Citrate Salt Form I of Compound 1, L-Malate Salt Form I of Compound 1, Mesylate Salt Form I of Compound 1, Mesylate Salt Form II of Compound 1, and Tosylate Salt Form I of Compound 1, or any combinations thereof.

82. A pharmaceutical composition comprising a crystalline form of any one of claims 1-81, and a pharmaceutically acceptable excipient.

83. A method of treating cancer in a subject in need thereof, the method comprising administering a crystalline form of any one of claims 1-81.

84. The method of claim 83, wherein the cancer is breast cancer, ovarian cancer, pancreatic cancer, prostate cancer, a hematological cancer, gastrointestinal cancer, or lung cancer.

85. A method of treating a cancer comprising a BRCA1 and / or a BRCA2 mutation in a subject in need thereof, the method comprising administering a crystalline form of any one of claims 1-81.

86. The method of claim 85, wherein the cancer is bladder cancer, brain & CNS cancers, breast cancer, cervical cancer, colorectal cancer, esophagus cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, kidney cancer, leukemia, lung cancer, melanoma, myeloma, oral cavity cancer, ovarian cancer, pancreatic cancer, prostate cancer, skin cancer, stomach cancer, thyroid cancer, or uterus cancer.

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