COMPOSITIONS COMPRISING ANTI-CD38 ANTIBODIES AND CARFILZOMIB
Disclosed herein are compositions and kits which comprise anti-CD38 antibodies and carfilzomib compounds. Also disclosed are methods for treating cancers, such as multiple myeloma, in subjects with the compositions and kits.
1 . A method of treating a cancer in a subject which comprises
administering one or more anti-CD38 antibodies and one or more carfilzomib compounds to the subject.
2 . The method of claim 1 , wherein the cancer is a hematological malignancy.
3 . The method of claim 1 , wherein the cancer is multiple myeloma.
4 . The method of claim 1 , wherein the cancer is a relapsed multiple myeloma or a refractory multiple myeloma.
5 . The method of claim 1 , wherein the one or more carfilzomib compounds is carfilzomib.
6 . The method of claim 1 , wherein the one or more anti-CD38 antibodies are administered in an effective amount, preferably a synergistic amount.
7 . The method of claim 1 , wherein the one or more anti-CD38 antibodies and/or the one or more carfilzomib compounds are administered in a therapeutically effective amount.
8 . The method of any one of claims 1 to 7 , wherein at least one of the one or more anti-CD38 antibodies is capable of killing a CD38 + cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC).
9 . The method of any one of claims 1 to 7 , wherein at least one of the one or more anti-CD38 antibodies comprises one or more complementarity-determining region having an amino acid sequence selected from the group consisting of SEQ ID NOs: 13, 14, 81, 15, 16, 17, 18, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35 and 36.
10 . The method of any one of claims 1 to 7 , wherein at least one of the one or more anti-CD38 antibodies is selected from the group consisting of:
a) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 13, 15 and either SEQ ID NO: 14 or SEQ ID NO: 81, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 16, 17 and 18;
b) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 25, 26 and 27, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 28, 29 and 30;
c) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 1, 2 and 3, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 4, 5 and 6;
d) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 7, 8 and 9, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 10, 11 and 12;
e) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 19, 20 and 21, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 22, 23 and 24; and
f) an antibody comprising a heavy chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 31, 32 and 33, and a light chain comprising three sequential CDRs having amino acid sequences consisting of SEQ ID NOs: 34, 35 and 36.
11 . The method of claim 10 , wherein said antibody comprises a heavy chain having a V H variable region represented by SEQ ID NO: 66, and a light chain having a V L variable region represented by either SEQ ID NO: 62 or SEQ ID NO: 64.
12 . The method of claim 10 , wherein said antibody comprises a heavy chain having a V H variable region represented by SEQ ID NO: 72, and a light chain having a V L variable region represented by either SEQ ID NO: 68 or SEQ ID NO: 70.
13 . The method of any one of claims 1 to 12 , wherein the one or more anti-CD38 antibodies is administered intravenously.
14 . The method of any one of claims 1 to 12 , wherein the one or more carfilzomib compounds is administered intravenously.
15 . The method of any one of claims 1 to 14 , wherein the one or more anti-CD38 antibodies and the one or more carfilzomib compounds are administered sequentially.
16 . The method of any one of claims 1 to 15 , and further comprising administering a dexamethasone compound, preferably dexamethasone, to the subject.
17 . The method of claim 16 , wherein the dexamethasone compound is administered orally.
18 . The method of any one of claims 16 to 17 , wherein the one or more anti-CD38 antibodies, the one or more carfilzomib compounds, and the dexamethasone compound are administered sequentially.
19 . A composition comprising
a) at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 + cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and
b) at least one carfilzomib compound, preferably carfilzomib; and, optionally
c) a dexamethasone compound, preferably dexamethasone.
20 . A kit comprising
a) a first composition comprising at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38 + cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and
b) a second composition comprising at least one carfilzomib compound, preferably carfilzomib.
21 . The kit of claim 20 , wherein the compositions are packaged for sequential administration to a subject.
22 . The kit of claim 20 or claim 21 , and further including a dexamethasone compound, preferably dexamethasone.
23 . The kit of claim 22 , wherein the dexamethasone compound is packaged for sequential administration to a subject.
24 . A kit comprising
at least one anti-CD38 antibody capable of killing a CD38 + cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC), packaged together with
a label having one or more messages that the at least one anti-CD38 antibody shall be administered in combination with carfilzomib, and optionally with dexamethasone.
25 . A combination of:
(i) at least one anti-CD38 antibody, preferably the antibody is capable of killing a CD38+ cell by apoptosis, antibody-dependent cell-mediated cytotoxicity (ADCC), and complement-dependent cytotoxicity (CDC); and
(ii) at least one carfilzomib compound, preferably carfilzomib; and, optionally
(iii) a dexamethasone compound, preferably dexamethasone.
26 . The combination of claim 25 , wherein the combination is for sequential use in the treatment of a hematological malignancy, preferably multiple myeloma.