Combination therapies using PRMT5 inhibitors for the treatment of cancer
This disclosure relates to methods of treating cancer. This disclosure further relates to treating cancer in a subject with compounds that are inhibitors of PRMT5, particularly in combination with KRAS G12C inhibitors.
1. A method for treating lung cancer in a subject, the method comprising:
administering to the subject a therapeutically effective amount of adagrasib and a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable salt thereof.
2. The method of claim 1 , wherein the lung cancer comprises methylthioadenosine phosphorylase (MTAP) gene homozygous deletion.
3. The method of claim 1 , wherein the lung cancer comprises KRASS′7° gene mutation.
4. The method of claim 2 , wherein the lung cancer further comprises a cyclin-dependent kinase inhibitor 2A (CDKN2A) gene homozygous deletion.
5. The method of claim 1 , wherein the therapeutically effective amount of the PRMT5 inhibitor is in the range of about 0.01 to 300 mg/kg per day.
6. The method of claim 1 , wherein the therapeutically effective amount of the PRMT5 inhibitor is in the range of about 0.1 to 100 mg/kg per day.
7. The method of claim 1 , wherein the therapeutically effective amount of the PRMT5 inhibitor is less than 50% of the clinically-established therapeutic amount.
8. The method of claim 1 , wherein the therapeutically effective amount of the KRAS G12C inhibitor is in the range of about 0.01 to 300 mg/kg per day.
9. The method of claim 1 , wherein the therapeutically effective amount of the KRAS G12C inhibitor is in the range of about 0.1 to 100 mg/kg per day.
10. The method of claim 1 , wherein the therapeutically effective amount of the KRAS G12C inhibitor is less than 50% of the clinically-established therapeutic amount.
11. The method of claim 1 , wherein the adagrasib and the MRTX-1719 or salt thereof are administered sequentially.
12. The method of claim 1 , wherein the adagrasib and the MRTX-1719 or salt thereof are administered simultaneously.
13. The method of claim 1 , wherein the subject previously received or completed a first-line chemotherapy.
14. The method of claim 13 , wherein the first-line chemotherapy is platinum-and/or taxane-based chemotherapy.
15. A method for reducing tumor volume in a subject suffering from lung cancer, the method comprising:
administering to the subject a therapeutically effective amount of adagrasib and a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable salt thereof.
16. A method for slowing tumor growth in a subject suffering from lung cancer, the method comprising:
administering to the subject a therapeutically effective amount of adagrasib and a therapeutically effective amount of a compound of the formula
or a pharmaceutically acceptable salt thereof.