Crystalline solid forms of salts of N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide, processes for making, and methods of use

1. Crystalline solid salts of N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (Compound 1), wherein the crystalline solid salts are selected from the group consisting of:

N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (Compound 1) ethane disulfonate, wherein

Compound 1 ⋅ ethane disulfonate is characterized as Form 4 and comprises Compound 1 and ethane disulfonate in a 1:1 molar ratio, and is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 6.83, 8.37, 11.67, 13.10, 13.65, 22.09, 22.48, 22.70, 24.66, and 27.19 degrees, or

Compound 1 ⋅ ethane disulfonate is characterized as Form 12 and comprises Compound 1 and ethane disulfonate in a 2:1 molar ratio, and is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 13.20, 13.75, 14.56, 16.45, 16.74, 18.07, 18.23, 20.18, 22.28, 23.46, 24.98, 25.69, 27.62, and 31.26 degrees;

N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (Compound 1) besylate, wherein Compound 1 ⋅ besylate is characterized as Form 6 and comprises Compound 1 and besylate in a 1:1 molar ratio, and is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 9.77, 10.52, 13.26, 14.34, 15.90, 15.98, 17.93, 18.69, 19.54, 22.83, 26.78, and 26.85 degrees; and

N-{4-[(6,7-dimethoxyquinolin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl) cyclopropane-1,1-dicarboxamide (Compound 1) gluconate, wherein Compound 1 ⋅ gluconate is characterized as Form 26 and comprises Compound 1 and gluconate in a 1:1 molar ratio, and is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 10.50, 10.59, 13.58, 13.98, 14.05, 18.71, 21.01, 22.59, 23.24, 24.35, 25.38, 25.46, 26.73, 26.88, 27.40, and 27.96 degrees.

2. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 4 of claim 1 , wherein the Form 4 is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 8.37, 11.67, 13.10, 22.48, 22.70, 24.66, and 27.19 degrees.

3. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 4 of claim 1 , wherein the Form 4 is characterized by peaks at 8.37, 11.67, 13.10, 22.48, 22.70, 24.66, and 27.19 degrees on a 2-theta scale in an XRPD pattern.

4. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 4 of claim 1 , wherein the Form 4 is characterized by an XRPD pattern according to FIG. 2 .

5. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 12 of claim 1 , wherein the Form 12 is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 13.20, 13.75, 14.56, 20.18, 22.28, 24.98, and 25.69 degrees.

6. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 12 of claim 1 , wherein the Form 12 is characterized by peaks at 13.20, 13.75, 14.56, 20.18, 22.28, 24.98, and 25.69 degrees on a 2-theta scale in an XRPD pattern.

7. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 12 of claim 1 , wherein the Form 12 is characterized by peaks at 13.20, 14.56, 20.18, 22.28, 24.98, and 25.69 degrees on a 2-theta scale in an XRPD pattern.

8. Crystalline solid Compound 1 ⋅ ethane disulfonate characterized as Form 12 of claim 1 , wherein the Form 12 is characterized by an XRPD pattern according to FIG. 4 .

9. Crystalline solid Compound 1 ⋅ besylate characterized as Form 6 of claim 1 , wherein the Form 6 is characterized by one or more peaks on a 2-theta scale in an XRPD pattern selected from the group consisting of 9.77, 10.52, 13.26, 14.34, 15.90, 18.69, 19.54, 22.83, 26.78, and 26.85 degrees.

10. Crystalline solid Compound 1 ⋅ besylate characterized as Form 6 of claim 1 , wherein the Form 6 is characterized by peaks on a 2-theta scale in an XRPD pattern at 9.77, 10.52, 13.26, 14.34, 15.90, 18.69, 19.54, 22.83, 26.78, and 26.85 degrees.

11. Crystalline solid Compound 1 ⋅ besylate characterized as Form 6 of claim 1 , wherein the Form 6 is characterized by an XRPD pattern according to FIG. 2 .

12. Crystalline solid Compound 1 ⋅ gluconate characterized as Form 26 of claim 1 , wherein the Form 26 is characterized by one or more peaks on a 2-theta scale in an XRPD pattern at 13.58, 13.98, 22.59, and 25.46 degrees.

13. Crystalline solid Compound 1 ⋅ gluconate characterized as Form 26 of claim 1 , wherein the Form 26 is characterized by peaks on a 2-theta scale in an XRPD pattern at 13.58, 13.98, 22.59, and 25.46 degrees.

14. Crystalline solid Compound 1 ⋅ gluconate characterized as Form 26 of claim 1 , wherein the Form 26 is characterized by peaks on a 2-theta scale in an XRPD pattern at 13.58, 13.98, 14.05, 22.59, 25.35, and 25.46 degrees.

15. Crystalline solid Compound 1 ⋅ gluconate characterized as Form 26 of claim 1 , wherein the Form 26 is characterized by an XRPD pattern according to FIG. 9 .

16. A pharmaceutical composition comprising a therapeutically effective amount of a substantially pure crystalline solid salt of Compound 1 as recited by claim 1 and a pharmaceutically acceptable carrier.

17. A method of treating cancer comprising administering to a subject a therapeutically effective amount of a substantially pure crystalline solid salt of Compound 1 as recited by claim 1 .

18. The method of claim 17 , wherein the cancer is selected from thyroid cancer, stomach cancer, esophageal carcinoma, kidney cancer, liver cancer, ovarian carcinoma, cervical carcinoma, bladder cancer, large bowel cancer, small bowel cancer, brain cancer, lung cancer, bone cancer, prostate carcinoma, pancreatic carcinoma, skin cancer, bone cancer, lymphoma, solid tumors, Hodgkin's disease, or non-Hodgkin's lymphoma.