Solid state forms
The present disclosure provides crystalline and amorphous forms of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one, including several anhydrous, hydrate and solvate forms, and solid state forms thereof, pharmaceutical compositions, and methods of treating a disease mediated by KRAS G12C inhibition.
1. A compound, wherein the compound is a crystalline anhydrous form of the M atropisomer of 6-fluoro-7-(2-fluoro-6-hydroxyphenyl)-1-(4-methyl-2-(2-propanyl)-3-pyridinyl)-4-((2S)-2-methyl-4-(2-propenoyl)-1-piperazinyl)pyrido[2,3-d]pyrimidin-2(1H)-one (Compound 1) and wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 9.0±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
2. The compound of claim 1 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 12.0±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
3. The compound of claim 1 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 12.6±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
4. The compound of claim 2 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 12.6±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
5. The compound of claim 1 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 19.0±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
6. The compound of claim 2 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 19.0±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
7. The compound of claim 3 , wherein the compound is characterized by an x-ray powder diffraction pattern comprising a peak at 19.0±0.2 degrees 2 theta as measured by using an x-ray wavelength of 1.54 Å.
8. A pharmaceutical composition comprising the compound of any one of claims 1 - 7 and a pharmaceutically acceptable excipient.
9. The pharmaceutical composition of claim 8 , wherein the pharmaceutical composition is a tablet.
10. The pharmaceutical composition of claim 9 , wherein the tablet comprises 120 mg of the compound.
11. A method of treating cancer having a KRAS G12C mutation in a patient in need thereof, the method comprising administering to the patient a therapeutically effective amount of the compound of any one of claims 1 - 7 , wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, small intestine cancer, appendix cancer, colorectal cancer, endometrial cancer, pancreatic cancer, liver cancer, small cell lung cancer, cervical cancer, germ cell tumor, ovarian cancer, pancreatic neuroendocrine tumor, bladder cancer, myelodysplastic/myeloproliferative neoplasms, head and neck cancer, esophageal cancer, soft tissue sarcoma, malignant mesothelioma, thyroid cancer, skin cancer, gastric cancer, nasal cavity cancer, or bile duct cancer.
12. The method of claim 11 , wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer, small intestine cancer, appendix cancer, colorectal cancer, endometrial cancer, pancreatic cancer, skin cancer, gastric cancer, nasal cavity cancer, or bile duct cancer.
13. The method of claim 11 , wherein the cancer having a KRAS G12C mutation is non-small cell lung cancer or colorectal cancer.
14. The method of claim 11 , wherein the cancer having a KRAS G12C mutation is pancreatic cancer or colorectal cancer.
15. The method of claim 11 , wherein the compound is administered to an adult.
16. The method of claim 13 , wherein the compound is administered to an adult.