Methods of treating cancers and enhancing efficacy of T cell redirecting therapeutics

1. A method of treating multiple myeloma in a subject, comprising administering a therapeutically effective amount of a BCMA×CD3 bispecific antibody to the subject to treat the multiple myeloma, wherein the subject is relapsed or refractory to treatment with a prior anti-cancer therapeutic, and wherein the BCMA×CD3 bispecific antibody consists of:

(i) one first heavy chain (HC 1), wherein the HC1 comprises an amino acid sequence having SEQ ID NO: 31, and one first light chain (LC1), wherein the LC1 comprises an amino acid sequence having SEQ ID NO: 32, and

(ii) one second heavy chain (HC2), wherein the HC2 comprises an amino acid sequence having SEQ ID NO: 41, and one second light chain (LC2), wherein the LC2 comprises an amino acid sequence having SEQ ID NO: 42.

2. The method of claim 1 , wherein the multiple myeloma is a high-risk multiple myeloma.

3. The method of claim 2 , wherein the subject having the high-risk multiple myeloma has one or more chromosomal abnormalities comprising:

a) t(4;14)(p16;q32);

b) t(14;16)(q32;q23);

c) del17p;

d) 1qAmp;

e) t(4;14)(p16;q32) and t(14;16)(q32;q23);

f) t(4;14)(p16;q32) and del17p;

g) t(14;16)(q32;q23) and del17p; or

h) t(4;14)(p16;q32), t(14;16)(q32;q23) and del17p, or any combination thereof.

4. A method of treating multiple myeloma in a subject, wherein the subject is refractory or relapsed to treatment with an anti-C38 antibody, lenalinomide, bortezomib, pomalidomide, carfilzomib, elotozumab, ixazomib, melphalan, thalidomide, or any combination thereof, the method comprising administering a therapeutically effective amount of a BCMA×CD3 bispecific antibody to the subject to treat the multiple myeloma, and wherein the BCMA×CD3 bispecific antibody consists of:

(i) one first heavy chain (HC 1), wherein the HC1 comprises an amino acid sequence having SEQ ID NO: 31, and one first light chain (LC1), wherein the LC1 comprises an amino acid sequence having SEQ ID NO: 32, and

(ii) one second heavy chain (HC2), wherein the HC2 comprises an amino acid sequence having SEQ ID NO: 41, and one second light chain (LC2), wherein the LC2 comprises an amino acid sequence having SEQ ID NO: 42.

5. The method of claim 4 , wherein the subject is relapsed to treatment with the anti-CD38 antibody.

6. The method of claim 4 , wherein the anti-CD38 antibody comprises a heavy chain complementarity determining region 1 (HCDR1) of SEQ ID NO: 6, a heavy chain complementarity determining region 2 (HCDR2) of SEQ ID NO: 7, a heavy chain complementarity determining region 3 (HCDR3) of SEQ ID NO: 8, a light chain complementarity determining region 1 (LCDR1) of SEQ ID NO: 9, a light chain complementarity determining region 2 (LCDR2) of SEQ ID NO: 10 and a light chain complementarity determining region 3 (LCDR3) of SEQ ID NO: 11.

7. The method of claim 6 , wherein the anti-CD38 antibody comprises a heavy chain variable region (VH) of SEQ ID NO: 4 and a light chain variable region (VL) of SEQ ID NO: 5.

8. The method of claim 7 , wherein the anti-CD38 antibody is an IgG1 isotype.

9. The method of claim 8 , wherein the anti-CD38 antibody comprises a heavy chain (HC) of SEQ ID NO: 12 and a light chain (LC) of SEQ ID NO: 13.

10. The method of claim 4 , wherein the anti-CD38 antibody comprises

a) a VH of SEQ ID NO: 14 and a VL of SEQ ID NO: 15;

b) a VH of SEQ ID NO: 16 and a VL of SEQ ID NO: 17;

c) a VH of SEQ ID NO: 18 and a VL of SEQ ID NO: 19; or

d) a VH of SEQ ID NO: 20 and a VL of SEQ ID NO: 21.

11. The method of claim 10 , wherein the anti-CD38 antibody is an IgG1 isotype.

12. The method of claim 1 , wherein the subject is a human.

13. The method of claim 1 , further comprising administering to the subject one or more anti-cancer therapies.

14. The method of claim 13 , wherein the one or more anti-cancer therapies is selected from the group consisting of an autologous stem cell transplant (ASCT), radiation, surgery, a chemotherapeutic agent, an immunomodulatory agent and a targeted cancer therapy.

15. The method of claim 14 , wherein the one or more anti-cancer therapies is selected from the group consisting of lenalidomide, thalidomide, pomalidomide, bortezomib, carfilzomib, elotozumab, ixazomib, melphalan, prednisone or dexamethasone, or any combination thereof.

16. The method of claim 4 , wherein the multiple myeloma is a high-risk multiple myeloma.

17. The method of claim 16 , wherein the subject having the high-risk multiple myeloma has one or more chromosomal abnormalities comprising:

a) t(4;14)(p16;q32);

b) t(14;16)(q32;q23);

c) del17p;

d) 1qAmp;

e) t(4;14)(p16;q32) and t(14;16)(q32;q23);

f) t(4;14)(p16;q32) and del17p;

g) t(14;16)(q32;q23) and del17p; or

h) t(4;14)(p16;q32), t(14;16)(q32;q23) and del17p, or any combination thereof.

18. The method of claim 1 or 4 , wherein the BCMA×CD3 bispecific antibody consists of the HC1 of SEQ ID NO: 31, the LC1 of SEQ ID NO: 32, the HC2 of SEQ ID NO: 41, and the LC2 of SEQ ID NO: 42.