Combination therapy with antibody-drug conjugates
View Patent ↗Methods for the treatment of Hodgkin's lymphoma comprising administering both a chemotherapeutic regimen and an antibody-drug conjugate compound to a subject in need thereof are provided.
1. A method for treating Hodgkin lymphoma in a subject, the method comprising administering to a subject in need thereof a chemotherapeutic regimen comprising doxorubicin, bleomycin, vinblastine and dacarbazine and an antibody-drug conjugate compound, wherein said antibody-drug conjugate is an anti-CD30 antibody conjugated to an auristatin compound and administration of said antibody-drug conjugate compound and chemotherapeutic regimen provides a synergistic effect in the treatment of Hodgkin lymphoma in the patient.
2. The method of claim 1 wherein said antibody-drug conjugate compound is delivered over a treatment cycle wherein the total dose over the treatment cycle is from about 0.1 mg/kg to about 3.8 mg/kg of the subject's body weight.
3. The method of claim 2 wherein the treatment cycle is three or four weeks.
4. The method of claim 1 wherein said antibody-drug conjugate compound is administered in a dose range of 0.2 to 1.2 mg/kg of the subject's body weight per dose.
5. The method of claim 1 wherein the antibody-drug conjugate compound and chemotherapeutic regimen comprising doxorubicin, bleomycin, vinblastine and dacarbazine are administered during a treatment cycle of three or four weeks and no additional anti-cancer agents are administered during the treatment cycle.
6. The method of claim 1 wherein said subject has relapsed or refractory Hodgkin lymphoma and has not previously been treated with said chemotherapeutic regimen.
7. The method of claim 1 wherein the antibody-drug conjugate compound is administered for two or more treatment cycles.
8. The method of claim 1 wherein the auristatin compound is conjugated to the anti-CD30 antibody via a linker that is cleavable under intracellular conditions, such that cleavage of the linker releases the auristatin compound from the antibody in the intracellular environment.
9. The method of claim 8 wherein the antibody-drug conjugate compound has the following structure:
wherein mAb-s- represents the anti-CD30 antibody and p ranges from 1 to about 10.
10. The method of claim 1 wherein the auristatin compound is conjugated to the anti-CD30 antibody via a linker that is not cleavable under intracellular conditions and the auristatin compound is released by antibody degradation.
11. The method of claim 10 wherein the antibody-drug conjugate compound has the following structure:
wherein mAb-s- represents the anti-CD30 antibody and p ranges from 1 to about 10.
12. The method of claim 1 wherein said anti-CD30 antibody is a chimeric AC10 antibody or competes for binding with a chimeric AC10 antibody.
13. The method of claim 12 wherein the anti-CD30 antibody is a chimeric AC10 antibody.