ANTI-CD37 IMMUNOCONJUGATE AND ANTI-CD20 ANTIBODY COMBINATIONS
Methods of administering immunoconjugates that bind to CD37 (e.g., IMGN529) in combination with antibodies that bind to CD20 are provided. The methods comprise administering an anti-CD37 immunoconjugate (e.g., IMGN529) and an anti-CD20 antibody to a person in need thereof, for example, a cancer patient.
1 . A method for treating a patient having a B-cell cancer comprising administering to said patient in need thereof an immunoconjugate that binds to CD37 comprising an antibody or antigen-binding fragment thereof comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences as set forth in SEQ ID NOs: 4-9, respectively; and an antibody or antigen-binding fragment thereof that binds to CD20, wherein said immunoconjugate that binds to CD37 is administered at a dose of about 0.7 mg/kg.
2 . (canceled)
3 . The method of claim 1 , wherein the immunoconjugate that binds to CD37 comprises an antibody or antigen-binding fragment thereof comprising the variable heavy chain sequence set forth in SEQ ID NO:12 and the variable light chain sequence set forth in SEQ ID NO:15.
4 . The method of claim 3 , wherein the antibody is huCD37-3.
5 . The method of claim 1 , wherein the immunoconjugate comprises a maytansinoid.
6 . The method of claim 5 , wherein the maytansinoid is DM1.
7 . The method of claim 5 , where the immunoconjugate comprises a non-cleavable linker.
8 . The method of claim 7 , wherein the linker is SMCC.
9 . The method of claim 1 , wherein the immunoconjugate that binds to CD37 is IMGN529.
10 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to CD20 is selected from the group consisting of rituximab, ofatumumab, obinutuzumab, and vetuzuamb.
11 - 16 . (canceled)
17 . A method for treating a patient having a B-cell cancer comprising administering to said patient in need thereof an immunoconjugate that binds to CD37 comprising an antibody or antigen-binding fragment thereof comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences as set forth in SEQ ID NOs: 4-9, respectively; and an antibody or antigen-binding fragment thereof that binds to CD20, and wherein the antibody or antigen-binding fragment thereof that binds to CD20 is not rituximab.
18 - 19 . (canceled)
20 . The method of claim 1 , wherein the immunoconjugate that binds to CD37 and the antibody or antigen-binding fragment thereof that binds to CD20 produce a synergistic effect, wherein the immunoconjugate that binds to CD37 and the antibody or antigen-binding fragment thereof that binds to CD20 produce a Synergy Score of at least 4 in vitro.
21 - 25 . (canceled)
26 . The method of claim 1 , wherein the immunoconjugate that binds to CD37 and the antibody or antigen-binding fragment thereof that binds to CD20 have a combination index value of less than 0.5.
27 - 30 . (canceled)
31 . The method of claim 1 , wherein the cancer is leukemia or lymphoma.
32 . The method of claim 1 , wherein the cancer is selected from the group consisting of B-cell lymphomas including NHL, precursor B-cell lymphoblastic leukemia/lymphoma and mature B-cell neoplasms, such as B-cell chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), B-cell prolymphocytic leukemia, lymphoplasmacytic lymphoma, mantle cell lymphoma (MCL), follicular lymphoma (FL), including low-grade, intermediate-grade and high-grade FL, cutaneous follicle center lymphoma, marginal zone B-cell lymphoma (MALT type, nodal and splenic type), hairy cell leukemia, diffuse large B-cell lymphoma (DLBCL), Burkitt's lymphoma, plasmacytoma, plasma cell myeloma, post-transplant lymphoproliferative disorder, Waldenstrom's macroglobulinemia, acute lymphoblastic leukemia (ALL), and anaplastic large-cell lymphoma (ALCL).
33 . (canceled)
34 . The method of claim 32 , wherein the NHL is relapsed or refractory NHL.
35 . The method of claim 34 , wherein the NHL is diffuse large B-cell lymphoma (DLBCL).
36 . The method of claim 35 , wherein the DLBCL is GCB DLBCL or ABC DLBCL.
37 - 42 . (canceled)
43 . The method of claim 1 , wherein the cancer overexpresses MYC or BCL2.
44 - 47 . (canceled)
48 . The method of claim 17 , wherein the immunoconjugate is administered at a dose of from about 0.1 mg/kg to about 2.8 mg/kg.
49 - 65 . (canceled)
66 . The method of claim 1 , wherein the immunoconjugate is administered once every three weeks.
67 . (canceled)
68 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to CD20 is administered at a dose of about 375 mg/m 2 .
69 . (canceled)
70 . The method of claim 1 , wherein the antibody or antigen-binding fragment thereof that binds to CD20 is administered on week 1, day 1 of a three week schedule.
71 - 72 . (canceled)
73 . The method of claim 1 , wherein the immunoconjugate that binds to CD37 and the antibody or antigen-binding fragment thereof that binds to CD20 are administered intravenously.
74 . The method of claim 1 further comprising administering a corticosteroid to the patient.
75 - 76 . (canceled)
77 . The method of claim 74 , wherein the corticosteroid is administered peri-infusionally.
78 . (canceled)
79 . The method of claim 74 , wherein the corticosteroid is administered at least one additional time after administration of the immunoconjugate.
80 - 83 . (canceled)
84 . The method of claim 74 , wherein the corticosteroid is selected from the group consisting of prednisone, prednisolone, methylprednisolone, beclamethasone, betamethasone, dexamethasone, fludrocortisone, hydrocortisone, and triamcinolone.
85 . (canceled)
86 . The method of claim 1 further comprising administering a growth factor to the patient.
87 . The method of claim 86 , wherein the growth factor is selected from the group consisting of granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage colony-stimulating factor (M-CSF), filgrastim, and pegfilgrastim.
88 - 92 . (canceled)
93 . The method of claim 1 , wherein the cancer expresses CD37, CD20, or CD37 and CD20.
94 . The method of claim 1 , wherein the immunoconjugate is IMGN529, wherein the immunoconjugate is administered at a dose of about 0.7 mg/kg once every three weeks, wherein the antibody or antigen-binding fragment thereof that binds to CD20 is rituximab, and wherein the antibody or antigen-binding fragment thereof that binds to CD20 is administered at a dose of about 375 mg/m 2 on week 1, day 1 of a three week schedule.
95 . A kit comprising a pharmaceutical composition comprising an immunoconjugate that binds to CD37 comprising an antibody comprising VH CDR1, VH CDR2, VH CDR3, VL CDR1, VL CDR2, and VL CDR3 sequences as set forth in SEQ ID NOs: 4-9, respectively; and instructions to administer the immunoconjugate and an anti-CD20 antibody or antigen-binding fragment thereof.
96 - 102 . (canceled)
103 . A method of instructing a human subject with cancer, the method comprising providing instructions to receive cancer treatment with an immunoconjugate that binds to CD37 and an antibody or antigen-binding fragment thereof that binds to CD20.
104 - 109 . (canceled)