BISPECIFIC ANTIBODY AGAINST CD3 AND CD20 IN COMBINATION THERAPY FOR TREATING DIFFUSE LARGE B-CELL LYMPHOMA

1 . A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject of a combination comprising epcoritamab or a biosimilar thereof, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone or prednisolone in 21-day cycles, wherein

(a) epcoritamab or biosimilar thereof is administered subcutaneously, wherein

(i) a priming dose is administered on day 1 of the first 21-day cycle, an intermediate dose is administered on day 8 of the first 21-day cycle, and a full dose of 24 or 48 mg on day 15 of the first 21-day cycle, wherein the priming dose and intermediate dose are at a lower dose as compared with the full dose,

(ii) a full dose of 24 or 48 mg on days 1, 8 and 15 of the second to fourth 21-day cycle, and

(iii) a full dose of 24 or 48 mg on day 1 of each subsequent 21-day cycle;

(b) polatuzumab vedotin is administered intravenously at a dose of 1.8 mg/kg on day 1 of each 21-day cycle;

(c) rituximab is administered intravenously at a dose of 375 mg/m 2 on day 1 of each 21-day cycle;

(d) cyclophosphamide is administered intravenously at a dose of 750 mg/m 2 day 1 of each 21-day cycle;

(e) doxorubicin is administered intravenously at a dose of 50 mg/m 2 on day 1 of each 21-day cycle; and

(f) prednisone or prednisolone is administered intravenously or orally at a dose of 100 mg/day on days 1-5 of each 21-day cycle;

wherein administration of the combination in 21-day cycles continues until the subject exhibits a complete response (CR) or until progressive disease develops or unacceptable toxicity occurs.

2 . The method of claim 1 , wherein the epcoritamab or biosimilar thereof is administered at a full dose of 24 mg.

3 . The method of claim 1 , wherein the epcoritamab or biosimilar thereof is administered at a full dose of 48 mg.

4 - 6 . (canceled)

7 . The method of claim 1 , wherein the administration of the full dose of epcoritamab or biosimilar thereof is performed on day 1 for at least cycles 4-8.

8 - 10 . (canceled)

11 . The method of claim 1 , wherein the priming dose of epcoritamab is 0.16 mg.

12 - 13 . (canceled)

14 . The method of claim 1 , wherein the intermediate dose is 0.8 mg.

15 - 16 . (canceled)

17 . The method of claim 1 , wherein the administration of polatuzumab vedotin is performed for six 21-day cycles.

18 - 24 . (canceled)

25 . The method of claim 1 , wherein the administration of cyclophosphamide is performed for six 21-day cycles.

26 - 28 . (canceled)

29 . The method of claim 1 , wherein the administration of doxorubicin is performed for six 21-day cycles.

30 - 33 . (canceled)

34 . The method of claim 1 , wherein prednisone or prednisolone is administered for six 21-day cycles.

35 - 45 . (canceled)

46 . The method of claim 1 , wherein the DLBCL is with histologically confirmed CD20+ disease.

47 . The method of claim 46 , wherein the DLBCL is high-grade B cell lymphoma with MYC and Bcl-2 and/or Bcl-6 translocations (double-hit or triple-hit).

48 . The method of claim 47 , wherein the DLBCL is follicular lymphoma Grade 3B.

49 . The method of claim 1 , wherein the subject has an International Prognostic Index (IPI) score of 2-5.

50 . The method of claim 1 , wherein the subject has not received prior therapy for DLBCL or follicular lymphoma Grade 3B.

51 - 62 . (canceled)

63 . The method of claim 1 , wherein the method comprises administering a biosimilar of epcoritamab comprising a heavy chain and a light chain comprising the amino acid sequences set forth in SEQ ID NOs: 24 and 25, respectively, and a heavy chain and a light chain comprising the amino acid sequences set forth in SEQ ID NOs: 26 and 27, respectively.

64 . The method of claim 1 , wherein the method comprises administering a biosimilar of epcoritamab comprising a heavy chain and a light chain consisting of the amino acid sequence of SEQ ID NOs: 24 and 25, respectively, and a heavy chain and a light chain consisting of the amino acid sequence of SEQ ID NOs: 26 and 27, respectively.

65 . (canceled)

66 . The method of claim 1 , wherein the method comprises administration of epcoritamab.

67 . A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject of a combination comprising epcoritamab, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone or prednisolone in 21-day cycles, wherein

(a) epcoritamab is administered subcutaneously

(i) at a priming dose of 0.16 mg on day 1 of the first 21-day cycle, at an intermediate dose of 0.8 mg on day 8 of the first 21-day cycle, and at a full dose of 24 on day 15 of the first 21-day cycle,

(ii) at a full dose of 24 mg on days 1, 8 and 15 of the second to fourth 21-day cycle, and

(iii) at a full dose of 24 mg on day 1 of each subsequent 21-day cycle;

(b) polatuzumab vedotin is administered at a dose of 1.8 mg/kg on day 1 of each 21-day cycle;

(c) rituximab is administered intravenously at a dose of 375 mg/m 2 on day 1 of each 21-day cycle;

(d) cyclophosphamide is administered intravenously at a dose of 750 mg/m 2 day 1 of each 21-day cycle;

(e) doxorubicin is administered intravenously at a dose of 50 mg/m 2 on day 1 of each 21-day cycle; and

(f) prednisone or prednisolone is administered intravenously or orally at a dose of 100 mg/day on days 1-5 of each 21-day cycle;

wherein administration of the combination in 21-day cycles continues until the subject exhibits a complete response (CR) or until progressive disease develops or unacceptable toxicity occurs.

68 . A method of treating diffuse large B-cell lymphoma (DLBCL) in a human subject, the method comprising administering to the subject of a combination comprising epcoritamab, polatuzumab vedotin, rituximab, cyclophosphamide, doxorubicin and prednisone or prednisolone in 21-day cycles, wherein

(a) epcoritamab is administered subcutaneously

(i) at a priming dose of 0.16 mg on day 1 of the first 21-day cycle, at an intermediate dose of 0.8 mg on day 8 of the first 21-day cycle, and at a full dose of 48 mg on day 15 of the first 21-day cycle,

(ii) at a full dose of 48 mg on days 1, 8 and 15 of the second to fourth 21-day cycle, and

(iii) at a full dose of 48 mg on day 1 of each subsequent 21-day cycle;

(b) polatuzumab vedotin is administered at a dose of 1.8 mg/kg on day 1 of each 21-day cycle;

(c) rituximab is administered intravenously at a dose of 375 mg/m 2 on day 1 of each 21-day cycle;

(d) cyclophosphamide is administered intravenously at a dose of 750 mg/m 2 day 1 of each 21-day cycle;

(e) doxorubicin is administered intravenously at a dose of 50 mg/m 2 on day 1 of each 21-day cycle; and

(f) prednisone or prednisolone is administered intravenously or orally at a dose of 100 mg/day on days 1-5 of each 21-day cycle;

wherein administration of the combination in 21-day cycles continues until the subject exhibits a complete response (CR) or until progressive disease develops or unacceptable toxicity occurs.