SHP2 inhibitor monotherapy and uses thereof
Provided herein are SHP2 inhibitors for use in the reduction of solid tumors in a method of treating cancer.
1. A method of treating cancer in a patient in need thereof, said method comprising administering to said patient a therapeutically effective amount of a compound having the structure of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof:
wherein said cancer is non-small cell lung cancer, esophageal cancer, stomach cancer, or brain tumor; and wherein said patient has failed at least one anti-cancer agent therapy, wherein said anti-cancer agent is an EGFR TK inhibitor.
2. The method of claim 1 , wherein said method comprises administering said compound to said patient as third, fourth, fifth, or sixth line of treatment.
3. The method of claim 1 , wherein said compound, or a pharmaceutically acceptable salt thereof is administered to said patient in need at about 5 mg/kg, about 10 mg/kg, about 15 mg/kg, about 20 mg/kg, or about 25 mg/kg.
4. The method of claim 1 , wherein said method comprises administering said compound to said patient as a regimen.
5. The method of claim 1 , wherein said method comprises administering said compound to said patient orally or by intraperitoneal methods.
6. The method of claim 4 , wherein said method comprises administering said compound to said patient daily.
7. The method of claim 6 , wherein said method comprises administering said compound to said patient once a day (QD), twice a day (BID), or three times a day (TID).
8. The method of claim 1 , wherein said method of treating cancer inhibits metastasis of said cancer in said patient.
9. The method of claim 1 , wherein said method of treating cancer prolongs the time to disease progression of said cancer in said patient.
10. The method of claim 1 , wherein said method of treating cancer prolongs the survival of said patient.
11. The method of claim 1 , wherein said method of treating cancer increases progression-free survival of said patient.
12. The method of claim 1 , wherein said method of treating cancer reduces tumor or tumor burden in said patient.
13. The method of claim 1 , wherein dual specificity phosphatase 6 (DUSP6) expression reduces to 48% compared to housekeeping genes.
14. The method of claim 1 , wherein dual specificity phosphatase 6 (DUSP6) expression levels can be used as a biomarker.
15. The method of claim 1 , wherein phosphorylated extracellular signal-regulated kinase (pERK) expression reduces to 95% compared to housekeeping genes.
16. The method of claim 1 , wherein said cancer is non-small cell lung cancer, esophageal cancer, stomach cancer, or brain tumor.
17. A method of decreasing tumor volume in a patient having non-small cell lung cancer, esophageal cancer, stomach cancer or brain tumor, wherein said patient has failed an EGFR TK inhibitor therapy, said method comprising administering to said patient a therapeutically effective amount of a compound having the structure of Formula (Ia), or a pharmaceutically acceptable salt or solvate thereof:
18. The method of claim 17 , wherein said tumor volume is decreased by about 10%, about 20%, about 30%, about 40% or about 50%.
19. The method of claim 17 , wherein said tumor volume is decreased by at least about 10%.
20. The method of claim 17 , wherein said compound, or a pharmaceutically acceptable salt thereof is administered to said patient in need at about 5 mg/kg, about 10 mg/kg, about 15 mg/kg, about 20 mg/kg, or about 25 mg/kg.
21. The method of claim 17 , wherein said method comprises administering said compound to said patient as a regimen.
22. The method of claim 17 , wherein said method comprises administering said compound to said patient orally or by intraperitoneal methods.
23. The method of claim 17 , wherein said method comprises administering said compound to said patient daily.
24. The method of claim 23 , wherein said method comprises administering said compound to said patient once a day (QD), twice a day (BID), or three times a day (TID).
25. The method of claim 21 , wherein said method comprises administering said compound to said patient for 7 days, 14 days or 21 days.
26. The method of claim 17 , wherein said patient is undergoing treatment for non-small cell lung cancer.