COMBINATION THERAPY USING ANTIBODY-DRUG CONJUGATES
The present disclosure relates to combinations of anti-CD19 antibody drug conjugates and anti-CD79b conjugates, and their use in therapy, such as treating proliferative disorders.
1 - 24 . (canceled)
25 . A method for treating a proliferative disorder in an individual, the method comprising administering to the individual an effective amount of an antibody drug conjugate (ADC) comprising an anti-CD19 antibody and a pyrrolobenzodiazepine (PBD) dimer and polatuzumab vedotin, wherein the PBD dimer is of formula (III):
wherein R LL is a linker for connection to the antibody.
26 . The method according to claim 25 , wherein the ADC has the following structure:
wherein Ab is the anti-CD19 antibody.
27 . The method according to claim 25 , wherein the anti-CD19 antibody comprises the complementarity-determining regions (CDRs) of SEQ ID NOs: 2 and 8.
28 . The method according to claim 25 , wherein the individual is human.
29 . The method according to claim 25 , wherein the individual has, or has been determined to have, a cancer which expresses CD19 or CD19+ve tumour-associated non-tumour cells.
30 . The method according to claim 29 , wherein the CD19+ve tumour-associated non-tumour cells are CD19+ve infiltrating cells.
31 . The method according to claim 25 , wherein the individual is undergoing treatment with polatuzumab vedotin.
32 . The method according to claim 25 , wherein the individual has undergone treatment with polatuzumab vedotin.
33 . The method according to claim 25 , wherein the individual is refractory to treatment, or further treatment, with polatuzumab vedotin.
34 . The method according to claim 25 , wherein the treatment with the ADC and polatuzumab vedotin has increased efficacy as compared to monotherapy with either the ADC or polatuzumab vedotin alone.
35 . The method according to claim 25 , wherein the disorder is characterised by the presence of a neoplasm comprising CD19+ve cells.
36 . The method according to claim 25 , wherein the disorder is cancer.
37 . The method according to claim 25 , wherein the disorder is selected from the group comprising: non-Hodgkin's Lymphoma, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma, (FL), Burkitt lymphoma, Mantle Cell lymphoma (MCL), chronic lymphatic lymphoma (CLL), Waldenström Macroglobulinemia (WM), and Marginal Zone B-cell lymphoma (MZBL), and leukemias such as Hairy cell leukemia (HCL), Hairy cell leukemia variant (HCL-v), chronic lymphocytic leukemia (CLL) including Richter syndrome, and Acute Lymphoblastic Leukaemia (ALL) such as Philadelphia chromosome-positive ALL (Ph+ALL) or Philadelphia chromosome-negative ALL (Ph-ALL).
38 . A composition comprising (i) an antibody drug conjugate (ADC) comprising an anti-CD19 antibody and a pyrrolobenzodiazepine (PBD) dimer, and (ii) polatuzumab vedotin, wherein the PBD dimer is of formula (III):
wherein R LL is a linker for connection to the antibody.
39 . The composition according to claim 38 , wherein the ADC has the following structure:
wherein Ab is the anti-CD19 antibody.
40 . The composition according to claim 38 , wherein the anti-CD19 antibody comprises the complementarity-determining regions (CDRs) of SEQ ID NOs: 2 and 8.
41 . A method of selecting an individual for treatment with an anti-CD19 antibody drug conjugate (ADC) comprising an anti-CD19 antibody and a pyrrolobenzodiazepine (PBD) dimer, wherein the individual is selected for treatment with the ADC if the individual has been treated or is being treated with polatuzumab vedotin.