Adjuvant therapy with an anti-ERBB2 antibody conjugated to a maytansiniod
The present application describes adjuvant therapy of nonmetastatic breast cancer using an anti-ErbB2 antibody conjugated to a maytansinoid.
1. A method of adjuvant therapy comprising administering to a human subject having HER2 positive cancer, following definitive surgery, anthracycline cyclophosphamide (AC) based chemotherapy, followed by sequential administration of a taxoid and an effective amount of an immunoconjugate comprising an anti-ErbB2 antibody conjugated to a maytansinoid.
2. The method of claim 1 , wherein the taxoid is paclitaxel or docetaxel.
3. The method of claim 1 wherein the anti-ErbB2 antibody specifically binds the extracellular domain of ErbB2.
4. The method of claim 3 wherein the anti-ErbB2 antibody specifically binds to the 4D5 epitope within the extracellular domain of ErbB2.
5. The method of claim 4 wherein the antibody is huMAb4D5-8.
6. The method of claim 5 wherein the maytansinoid is DM1 having the following structure
and wherein the antibody is chemically linked to the maytansinoid via a disulfide or thioether group at “R” shown in the structure.
7. The method of claim 5 , wherein the immunoconjugate comprises from 3 to 5 maytansinoid molecules per antibody molecule.
8. The method of claim 5 , wherein the antibody and the maytansinoid are conjugated by a chemical linker selected from N-succinimidyl-3-(2-pyridyldithio)propionate, N-succinimidyl-4-(2-pyridylthio)pentanoate (SPP) and succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC).
9. The method of claim 6 or 8 , wherein the antibody and the maytansinoid are conjugated by succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate.
10. The method of claim 5 , wherein the HER2 positive cancer is HER2 positive breast cancer.
11. The method of claim 1 , claim 5 , or claim 10 , wherein said administration extends disease free survival (DFS) or overall survival (OS) in the subject.
12. The method of claim 10 , wherein the HER2 positive cancer is nonmetastatic HER2 positive breast cancer.
13. The method of claim 10 , wherein the immunoconjugate is administered in combination with an anti-ErbB2 antibody.
14. The method of claim 13 , wherein the anti-ErbB2 antibody is a HER2 dimerization inhibitor.
15. The method of claim 14 , wherein the HER2 dimerization inhibitor is pertuzumab.