Bispecific antibodies against CD3 and CD20
The present invention relates to bispecific antibodies (bsAbs) and the use of such antibodies in the treatment of disease in subjects. Moreover, advantageous treatment regimens are provided for the treatment of B-cell Non-Hodgkin Lymphoma (B-NHL).
1 . A method of treating a B-cell non-Hodgkin lymphoma (B-NHL) in a human subject, the method comprising subcutaneously administering a dose of 0.16 mg of epcoritamab to the subject on day one (1) of treatment and subcutaneously administering a dose of 0.8 mg of epcoritamab to the subject on day eight (8) of treatment,
wherein the subject does not experience cytokine release syndrome (CRS) or experiences manageable cytokine release syndrome of grade 1 or grade 2, and
wherein after day eight (8) of treatment a dose of 48 mg of epcoritamab is subcutaneously administered in intervals to the subject until progressive disease develops or unacceptable toxicity occurs.
2 . The method of claim 1 , wherein 48 mg of epcoritamab is administered subcutaneously to the human subject on days 15 and 22 of treatment.
3 . The method of claim 1 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL).
4 . The method of claim 3 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
5 . The method of claim 3 , wherein said B-NHL is mantle cell lymphoma (MCL).
6 . The method of claim 3 , wherein said B-NHL is follicular lymphoma (FL).
7 . The method of claim 3 , wherein said B-NHL is marginal-zone lymphoma (MZL).
8 . The method of claim 3 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
9 . The method of claim 3 , wherein said B-NHL is relapsed or refractory B-NHL.
10 . The method of claim 3 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
11 . The method of claim 1 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least one prior line of treatment for the B-NHL.
12 . The method of claim 1 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least two prior lines of treatment for the B-NHL.
13 . The method of claim 2 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL), and wherein the patient achieves a complete response (CR).
14 . The method of claim 13 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
15 . The method of claim 13 , wherein said B-NHL is mantle cell lymphoma (MCL).
16 . The method of claim 13 , wherein said B-NHL is follicular lymphoma (FL).
17 . The method of claim 13 , wherein said B-NHL is marginal-zone lymphoma (MZL).
18 . The method of claim 13 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
19 . The method of claim 13 , wherein said B-NHL is relapsed or refractory B-NHL.
20 . The method of claim 13 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
21 . A method of treating a B-cell non-Hodgkin lymphoma (B-NHL) in a human subject, the method comprising administering epcoritamab subcutaneously in 28-day cycles, wherein:
a) a priming dose of 0.16 mg is administered on day 1, an intermediate dose of 0.8 mg is administered on day 8, and a full dose of 48 mg is administered on days 15 and 22 of the first cycle;
b) a full dose of 48 mg is administered on days 1, 8, 15 and 22 of cycles 2-3;
c) a full dose of 48 mg is administered on days 1 and 15 of cycles 4-9; and
d) a full dose of 48 mg is administered on day 1 of subsequent cycles until progressive disease develops or unacceptable toxicity occurs.
22 . The method of claim 21 , wherein said B-NHL is selected from the group consisting of diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBCL), primary mediastinal large B-cell lymphoma (PMBCL), mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal-zone lymphoma (MZL), chronic lymphocytic leukemia (CLL), and small lymphocytic lymphoma (SLL).
23 . The method of claim 22 , wherein said B-NHL is diffuse large B-cell lymphoma (DLBCL).
24 . The method of claim 22 , wherein said B-NHL is mantle cell lymphoma (MCL).
25 . The method of claim 22 , wherein said B-NHL is follicular lymphoma (FL).
26 . The method of claim 22 , wherein said B-NHL is marginal-zone lymphoma (MZL).
27 . The method of claim 22 , wherein said B-NHL is small lymphocytic lymphoma (SLL).
28 . The method of claim 22 , wherein said B-NHL is relapsed or refractory B-NHL.
29 . The method of claim 22 , wherein said B-NHL is chronic lymphocytic lymphoma (CLL).
30 . The method of claim 21 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least one prior line of treatment for the B-NHL.
31 . The method of claim 21 , wherein prior to the day 1 of treatment with epcoritamab the human subject has received at least two prior lines of treatment for the B-NH.