Sheddase inhibitors combined with CD30-binding immunotherapeutics for the treatment of CD30 positive diseases
View Patent ↗The present invention is directed to pharmaceutical methods for the treatment of CD30 positive diseases, such as Hodgkin's disease, by administration of a combination of at least one sheddase inhibitor and at least one anti-CD30 immunotherapeutic.
1. A method of treating a disease characterized by expression of CD30 or CD30 shedding selected from lymphoma, T-cell leukemia, and adult T-cell leukemia (ATL) in a human patient, comprising administering to said human patient:
i) an antibody or antibody-conjugate which binds CD30; and
ii) methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate, or a pharmaceutically acceptable salt thereof;
wherein the amount of said methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2,5]octane-5-carboxylate, or said pharmaceutically acceptable salt thereof, and said antibody or antibody-conjugate together provide a therapeutically effective amount.
2. The method of claim 1 wherein said lymphoma is Hodgkin's disease (HD), Burkitt's lymphoma, anaplastic large-cell lymphoma (ALCL), cutaneous T-cell lymphoma, nodular small cleaved-cell lymphoma, lymphocytic lymphoma, peripheral T-cell lymphomas, Lennert's lymphoma, immunoblastic lymphoma, or entroblastic/centrocytic follicular lymphoma.
3. The method of claim 1 wherein said disease is T cell leukemia or adult T-cell leukemia (ATL).
4. The method of claim 1 wherein an antibody which binds CD30 is administered.
5. The method of claim 4 wherein said antibody is a monoclonal antibody.
6. The method of claim 4 wherein said antibody is a human, humanized, or chimeric antibody.
7. The method of claim 1 wherein an antibody-conjugate which binds CD30 is administered.
8. The method of claim 7 wherein said antibody-conjugate is an anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.
9. The method of claim 8 wherein said antibody-conjugate is a monoclonal anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.
10. The method of claim 9 wherein said antibody-conjugate is a human, humanized, or chimeric anti-CD30 antibody conjugated with a cytotoxin or radiotoxin.
11. The method of claim 1 wherein said administering is carried out such that the physiological effects of both said methyl (6S,7S)-7-[(hydroxyamino)carbonyl]-6-[(4-phenylpiperazin-1-yl)carbonyl]-5-azaspiro[2.5]octane-5-carboxylate, or said pharmaceutically acceptable salt thereof, and said antibody or antibody conjugate overlap in said patient.
12. The method of claim 1 , wherein said disease is lymphoma.