ANTI-CD47 BASED TREATMENT OF BLOOD CANCER
Methods, kits, and compositions are provided herein for determining the eligibility of a subject to receive an anti-CD47 treatment based on a presence or absence of B-cells in the subject, and subsequently treating the eligible subject with the anti-CD47 treatment alone or in combination with one or more additional agent such as an anti-CD20 antibody.
1 . A method of treating a blood cancer in a subject comprising: (a) administering an anti-CD47 agent that inhibits binding between CD47 and SIRPα; and (b) administering an anti-CD20 antibody to the subject, wherein B-cells are determined or have been determined to be present in the subject prior to performing steps (a) and (b).
2 . A method of treating a blood cancer in a subject comprising:
determining or having determined that B-cells are present in the subject; and
administering or having administered to the subject (i) an anti-CD47 agent that inhibits binding between CD47 and SIRPα and (ii) an anti-CD20 antibody.
3 .- 4 . (canceled)
5 . The method of claim 1 , wherein the determination that B-cells are present in the subject comprises determining or having determined that the subject has CD19+ B-cells.
6 .- 10 . (canceled)
11 . The method of claim 1 , wherein the determination that B-cells are present in the subject comprises determining or having determined that the subject has CD20+ B-cells.
12 .- 16 . (canceled)
17 . The method of claim 1 , wherein the determination that B-cells are present in the subject comprises determining or having determined that the subject has both CD19+ B-cells and CD20+ B-cells.
18 .- 20 . (canceled)
21 . The method of claim 1 , wherein the determination that B-cells are present in the subject comprises determining or having determined that the subject previously received an anti-CD20 therapy more than a threshold amount of time ago.
22 . The method of claim 21 , wherein the threshold amount of time is at least 4 weeks.
23 .- 34 . (canceled)
35 . The method of claim 1 , wherein the anti-CD47 agent comprises an anti-CD47 antibody or an anti-SIRPα antibody.
36 . The method of claim 35 , wherein the anti-CD47 agent comprises or is magrolimab.
37 . (canceled)
38 . The method of claim 1 , wherein the blood cancer is diffuse large B-cell lymphoma (DLBCL).
39 . The method of claim 38 , wherein the subject has relapsed or refractory DLBCL.
40 . The method of claim 39 , wherein the subject has previously been treated with at least two prior lines of therapy.
41 . The method of claim 1 , wherein the blood cancer is follicular lymphoma (FL) or marginal zone lymphoma.
42 . The method of claim 1 , wherein the blood cancer is non-Hodgkin's lymphoma.
43 . (canceled)
44 . The method of claim 1 , wherein the anti-CD47 agent is administered intravenously.
45 . The method of claim 1 , wherein the anti-CD20 antibody is administered intravenously.
46 .- 59 . (canceled)
60 . The method of claim 1 , wherein the anti-CD20 antibody comprises or is rituximab.
61 .- 66 . (canceled)
67 . The A-method of claim 1 ,
wherein the anti-CD47 agent comprises or is magrolimab; and
wherein the anti-CD20 antibody comprises or is rituximab,
wherein administering magrolimab comprises (1) administering a priming dose of magrolimab in the range of 1 mg to 10 mg of antibody per kg of body weight on Day 1, (2) administering weekly doses of magrolimab of at least 30 mg per kg of body weight for 8 weeks, and (3) administering every-other-week doses of magrolimab of at least 30 mg per kg of body weight onwards, and
wherein administering rituximab comprises (1) administering a weekly dose of rituximab at about 375 mg per m 2 of body surface area for 4 weeks and subsequently (2) administering monthly rituximab at about 375 mg per m 2 of body surface area.
68 . (canceled)
69 . A method comprising:
obtaining a sample from a subject with a blood cancer;
determining whether B-cells are present in the subject by performing an assay on the obtained sample from the subject,
wherein a presence of B-cells in the subject indicates that the subject is likely to respond to a therapy comprising 1) an anti-CD47 agent that inhibits binding between CD47 and SIRPα and 2 ) an anti-CD20 antibody,
wherein an absence of B-cells in the subject indicates that the subject is unlikely to respond to a therapy comprising 1) the anti-CD47 agent that inhibits binding between CD47 and SIRPα and 2) the anti-CD20 antibody.
70 . The method of claim 69 , wherein the sample obtained from the subject is a peripheral blood sample.
71 .- 133 . (canceled)