CPC C07K 16/2878 (2013.01) [A61K 31/454 (2013.01); A61K 31/573 (2013.01); A61K 39/3955 (2013.01); A61K 39/39558 (2013.01); A61P 35/00 (2018.01); C07K 16/2809 (2013.01); C07K 16/2896 (2013.01); C07K 16/30 (2013.01); A61K 2039/507 (2013.01); A61K 2039/545 (2013.01); C07K 2317/31 (2013.01)] | 10 Claims |
1. A method of treating multiple myeloma in a human subject in need thereof, comprising administering to the subject a BCMAxCD3 bispecific antibody and an anti-CD38 antibody in 28-day treatment cycles, wherein the method comprises:
subcutaneously administering to the subject the BCMAxCD3 bispecific antibody in step-up doses of 0.06 mg/kg and 0.3 mg/kg followed by a dose of 1.5 mg/kg once per week during treatment cycle 1, a dose of 1.5 mg/kg once per week during treatment cycle 2, and a dose of 3 mg/kg once every two weeks beginning in treatment cycle 3, and
subcutaneously administering to the subject the anti-CD38 antibody at a dose of 1800 mg once per week during treatment cycles 1 and 2, once every two weeks during treatment cycles 3-6 and once every 4 weeks beginning in treatment cycle 7,
wherein the BCMAxCD3 bispecific antibody comprises:
(1) a BCMA binding domain comprising a heavy chain variable region (VH) having heavy chain complementarity determining regions (HCDRs) HCDR1, HCDR2 and HCDR3 of the amino acid sequences of SEQ ID NO: 18, SEQ ID NO: 19, and SEQ ID NO: 20, respectively, and a light chain variable region (VL) having light chain complementarity determining regions (LCDRs) LCDR1, LCDR2 and LCDR3 of the amino acid sequences of SEQ ID NO: 21, SEQ ID NO: 22, and SEQ ID NO: 23, respectively, and
(2) a CD3 binding domain comprising a VH having HCDR1, HCDR2 and HCDR3 of the amino acid sequences of SEQ ID NO: 28, SEQ ID NO: 29, and SEQ ID NO: 30, respectively, and a VL having LCDR1, LCDR2 and LCDR3 of the amino acid sequences of SEQ ID NO: 31, SEQ ID NO: 32, and SEQ ID NO: 33, respectively,
wherein the method is effective in treating the multiple myeloma.
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