COMBINATION OF PROTEASOME INHIBITORS AND ANTI-CD30 ANTIBODIES
The present invention relates to methods for the treatment of cancers. In particular, the invention provides methods for treatment of cancer by administering a proteasome inhibitor in combination with an anti-CD30 antibody.
1 . A method of treating a patient suffering from a lymphoma, comprising administering to the subject a therapeutically effective amount of a proteasome inhibitor in combination with a therapeutically effective amount of an anti-CD30 antibody-drug conjugate; wherein the proteasome inhibitor is a compound of formula (I):
or a pharmaceutically acceptable salt, stereoisomeric or tautomeric form thereof, wherein:
ring A is selected from
and
Z 1 and Z 2 are each independently hydroxyl; or Z 1 and Z 2 together form a cyclic boronic ester having 2-20 carbon atoms, and optionally one or more heteroatoms selected from N, S, or O.
2 . The method of claim 1 , wherein the proteasome inhibitor is administered simultaneously, separately, sequentially or consecutively with the anti-CD30 antibody-drug conjugate.
3 . The method of claim 1 , wherein the lymphoma is Hodgkin lymphoma.
4 . The method of claim 1 , wherein the lymphoma is peripheral T-cell lymphoma (PTCL).
5 . The method of claim 1 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL).
6 . The method of claim 1 , wherein the lymphoma is anaplastic large cell lymphoma (ALCL).
7 . The method of claim 1 , wherein the lymphoma is cutaneous T-cell lymphoma
8 . The method of any of claims 1 - 7 wherein the proteosome inhibitor is a compound of formula (IIIa):
or a pharmaceutically acceptable salt thereof.
9 . The method of any of claims 1 - 7 , wherein the anti-CD30 antibody-drug conjugate is an anti-CD30 antibody conjugated to an auristatin compound.
10 . The method of claim 9 , wherein the auristatin compound is selected from the group consisting of MMAE and MMAF.
11 . The method of claim 9 , wherein the anti-CD30 antibody-drug conjugate is brentuximab vedotin.
12 . A method of treating a patient suffering from a lymphoma, comprising administering to the subject a therapeutically effective amount of a compound of formula (IIIa):
or a pharmaceutically acceptable salt thereof simultaneously with or consecutively with brentuximab vedotin.
13 . The method of claim 12 wherein the lymphoma is Hodgkin lymphoma.
14 . The method of claim 12 , wherein the lymphoma is peripheral T-cell lymphoma (PTCL).
15 . The method of claim 12 , wherein the lymphoma is diffuse large B-cell lymphoma (DLBCL).
16 . The method of claim 12 , wherein the lymphoma is anaplastic large cell lymphoma (ALCL).
17 . The method of any one of claims 12 - 16 , wherein the therapeutically effective amount of the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof is about 1.5 mg, 2.3 mg, 3.0 mg, 4.0 mg, 5.3 mg, or 5.5 mg, measured as the amount of the compound of formula (IV):
18 . The method of any one of claims 12 - 16 , wherein the therapeutically effective amount of brentuximab vedotin is about 1.0 mg/kg to 2.0 mg/kg of the patient's body weight per dose.
19 . The method of any one of claims 12 - 18 , wherein the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof is administered on days 1, and 8 of a 21-day cycle and bretuximab vedotin is administered on day 1 of a 21-day cycle.
20 . The method of any one of claims 12 - 18 , wherein the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof is administered on days 1, 8, and 15 of a 21-day cycle and bretuximab vedotin is administered on day 1 of a 21-day cycle.
21 . The method of any one of claims 12 - 18 , wherein the compound of formula (IIIa) or a pharmaceutically acceptable salt thereof is administered on days 1, 8, and 15 of a 28-day cycle and bretuximab vedotin is administered on day 1 of a 28-day cycle.