Treatment of HER2 positive cancers
In one aspect, the present invention provides a method for treating or ameliorating the effects of a HER2 positive cancer in a subject. In some embodiments, the method comprises administering a combination therapy comprising an anti-HER2 antibody and tucatinib. In some embodiments, the method further comprises administering a chemotherapeutic agent (e.g., an antimetabolite) to the subject. Pharmaceutical compositions and kits are also provided herein.
1. A method for treating a HER2-positive colorectal cancer in a human subject, the method comprising:
administering a combination therapy comprising an anti-HER2 antibody and tucatinib, thereby treating the HER2-positive colorectal cancer.
2. The method of claim 1 , wherein the anti-HER2 antibody is a member selected from the group consisting of trastuzumab, pertuzumab, ado-trastuzumab emtansine, margetuximab, and a combination thereof.
3. The method of claim 1 , wherein the anti-HER2 antibody is trastuzumab.
4. The method of claim 3 , wherein the trastuzumab is administered intravenously or subcutaneously.
5. The method of claim 3 , wherein the trastuzumab is administered at an amount of about 6 mg to 8 mg per kg of the subject's body weight once every three weeks.
6. The method of claim 3 , wherein the tucatinib is administered orally.
7. The method of claim 4 , wherein the tucatinib is administered orally.
8. The method of claim 5 , wherein the tucatinib is administered orally.
9. The method of claim 3 , wherein the tucatinib is administered in an amount of about 300 mg twice per day.
10. The method of claim 4 , wherein the tucatinib is administered in an amount of about 300 mg twice per day.
11. The method of claim 5 , wherein the tucatinib is administered in an amount of about 300 mg twice per day.
12. The method of claim 3 , wherein the HER2-positive colorectal cancer is an unresectable locally advanced colorectal cancer or a metastatic colorectal cancer.
13. The method of claim 9 , wherein the HER2-positive colorectal cancer is an unresectable locally advanced colorectal cancer or a metastatic colorectal cancer.
14. The method of claim 3 , wherein the HER2-positive colorectal cancer comprises a cell that has a wild-type KRAS exon 2 genotype, a wild-type NRAS genotype, or a wild-type BRAF genotype.
15. The method of claim 9 , wherein the HER2-positive colorectal cancer comprises a cell that has a wild-type KRAS exon 2 genotype, a wild-type NRAS genotype, or a wild-type BRAF genotype.
16. The method of claim 3 , wherein the subject has a HER2-positive colorectal cancer which is relapsed or refractory to a standard of care.
17. The method of claim 9 , wherein the subject has a HER2-positive colorectal cancer which is relapsed or refractory to a standard of care.
18. The method of claim 3 , wherein treating the subject results in a tumor growth inhibition (TGI) index of at least about 85%.
19. The method of claim 9 , wherein treating the subject results in a tumor growth inhibition (TGI) index of at least about 85%.
20. The method of claim 3 , wherein the combination of the trastuzumab and tucatinib is synergistic.
21. The method of claim 9 , wherein the combination of the trastuzumab and tucatinib is synergistic.
22. The method of claim 1 , wherein the anti-HER2 antibody is trastuzumab; wherein the trastuzumab is administered intravenously or subcutaneously at an amount of about 6 mg to 8 mg per kg of the subject's body weight once every three weeks; and wherein the tucatinib is administered orally in an amount of about 300 mg twice per day.
23. The method of claim 3 , wherein the combination therapy further comprises a chemotherapeutic agent.