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CN-121985964-A - Medicine for treating non-Hodgkin lymphoma, medicine combination and application thereof

CN121985964ACN 121985964 ACN121985964 ACN 121985964ACN-121985964-A

Abstract

The use of an anti-CD 20 antibody drug conjugate or a pharmaceutical combination thereof in the manufacture of a medicament for the treatment of non-hodgkin's lymphoma, the pharmaceutical combination comprising an anti-CD 20 antibody drug conjugate and at least one therapeutic agent, the anti-CD 20 antibody drug conjugate or the pharmaceutical combination therapy comprising the same having a superior therapeutic effect compared to the existing clinical second line standard therapy.

Inventors

  • HUANG KAI
  • HUANG JINGYAO

Assignees

  • 浙江特瑞思药业股份有限公司

Dates

Publication Date
20260505
Application Date
20240920
Priority Date
20230921

Claims (20)

  1. Use of an anti-CD 20 antibody drug conjugate in the manufacture of a medicament for the treatment of non-hodgkin's lymphoma, wherein the anti-CD 20 antibody drug conjugate has the structure: Wherein, mAb represents recombinant anti-CD 20 monoclonal antibody, and the drug-antibody ratio DAR is 4.2+ -1, preferably 4.2+ -0.5.
  2. The use of claim 1, wherein the non-hodgkin's lymphoma is relapsed or refractory non-hodgkin's lymphoma.
  3. The use of claim 2, wherein the non-hodgkin's lymphoma is a relapsed or refractory non-hodgkin's lymphoma after receiving at least one standard of care regimen.
  4. The use of claim 3, wherein the recombinant anti-CD 20 mab is selected from Rituximab (Rituximab) or a biosimilar thereof, ofatumumab (Ofatumumab) or a biosimilar thereof, ocrelizumab (Ocrelizumab) or a biosimilar thereof, obabine You Tuozhu mab (Obinutuzumab) or a biosimilar thereof.
  5. The use of claim 4, wherein the recombinant anti-CD 20 mab is selected from Rituximab (Rituximab) or a biological analogue thereof.
  6. The use according to any one of claims 1 to 5, wherein the non-hodgkin's lymphoma is selected from small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, marginal zone B-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, burkitt's lymphoma, mantle cell lymphoma, precursor (peripheral) large granular lymphocytic leukemia or anaplastic large cell lymphoma.
  7. The use of claim 6, wherein the non-hodgkin's lymphoma is diffuse large B-cell lymphoma.
  8. The use of claim 7, wherein the diffuse large B-cell lymphoma is CD20 positive diffuse large B-cell lymphoma.
  9. The use of claim 8, wherein the CD20 positive diffuse large B-cell lymphoma is a MYC and BCL2 double-expressed diffuse large B-cell lymphoma.
  10. The use of any one of claims 1-9, wherein the at least one standard of care regimen comprises at least anti-CD 20 antibody monotherapy or anti-CD 20 antibody combination therapy.
  11. The use of claim 10, wherein the at least one standard treatment regimen comprises at least one selected from the group consisting of R-CHOP, R-CHOEP, R-miniCHOP, DA-EPOCH-R, and Pola-R-CHP.
  12. The use of claim 11, wherein the at least one standard treatment regimen is R-CHOP.
  13. The use of any one of claims 1 to 12, wherein the anti-CD 20 antibody drug conjugate is used in combination with bendamustine.
  14. A pharmaceutical combination for use in the treatment of non-hodgkin's lymphoma, wherein the pharmaceutical combination is a combination of an anti-CD 20 antibody drug conjugate and bendamustine, the anti-CD 20 antibody drug conjugate having the structure: Wherein, mAb represents recombinant anti-CD 20 monoclonal antibody, and the drug-antibody ratio DAR is 4.2+ -1, preferably 4.2+ -0.5.
  15. The pharmaceutical combination of claim 14, wherein the non-hodgkin's lymphoma is relapsed or refractory non-hodgkin's lymphoma.
  16. The pharmaceutical combination of claim 15, wherein the non-hodgkin's lymphoma is a relapsed or refractory non-hodgkin's lymphoma after receiving at least one standard of care regimen.
  17. The pharmaceutical combination according to any one of claims 14-16, wherein the recombinant anti-CD 20 mab is selected from Rituximab (Rituximab) or a biosimilar thereof, ofatumumab (Ofatumumab) or a biosimilar thereof, oxrelizumab (Ocrelizumab) or a biosimilar thereof, obbine You Tuozhu mab (Obinutuzumab) or a biosimilar thereof.
  18. The pharmaceutical combination of claim 17, wherein the recombinant anti-CD 20 mab is selected from Rituximab (Rituximab) or a biological analogue thereof.
  19. A method of treating non-hodgkin's lymphoma comprising administering to a subject an effective amount of a pharmaceutical combination according to any one of claims 14-18 or an anti-CD 20 antibody drug conjugate according to any one of claims 14-18.
  20. The combination therapy of claim 19, wherein the non-hodgkin's lymphoma is selected from the group consisting of small lymphocytic lymphoma, B-cell chronic lymphocytic leukemia, marginal zone B-cell lymphoma, follicular lymphoma, diffuse large B-cell lymphoma, burkitt's lymphoma, mantle cell lymphoma, precursor (peripheral) large granular lymphocytic leukemia, and anaplastic large cell lymphoma.

Description

Medicine for treating non-Hodgkin lymphoma, medicine combination and application thereof Cross Reference to Related Applications The present patent application claims the priority benefit of the chinese invention patent application of application number CN 202311225386.1 filed at 2023, 9 and 21, the entire contents of which are incorporated herein by reference. Technical Field The invention relates to the technical field of pharmacy and drug combination, in particular to a drug for treating non-Hodgkin lymphoma, a drug combination and application thereof. Background Non-Hodgkin lymphoma (NHL) is the seventh largest cancer type worldwide, accounting for about 4% to 5% of new cancer cases and 3% to 4% of cancer-related deaths, affecting about 150 tens of thousands of people worldwide. NHL is a collective term for a group of malignant proliferative diseases of the lymphatic system, including numerous types of lymphomas, which originate mainly from B lymphocytes (> 85%), and rarely from T cells and natural killer cells. It is generally classified as slow-progressing or Indolent NHL (iNHL), fast-progressing or aggressive NHL (ahhl) by prognosis, with Follicular Lymphoma (FL) being the most common iNHL accounting for about 1/5 of total NHL patients, and diffuse large B-cell lymphoma (DLBCL) being the most common aNHL accounting for about 1/3 of total NHL patients. 30% -35% Of DLBCL in DLBCL expresses MYC protein, 20-35% simultaneously expresses BCL2, called 'double expression lymphoma', indicating poor prognosis. The use of drugs for improving the disease treatment effect is a conventional thinking in the field, however, clinical standard drug combination treatment schemes adopted for non-hodgkin lymphomas with different line numbers and different subtypes are different, the drug combination schemes in research are more, chemical drugs and biological drug varieties which can be used for combination are more complicated, so that the design of the drug combination scheme is difficult, and the curative effect and safety of the drug combination are very uncertain. WO2021223048A1 and chinese homologs CN115485304A disclose an anti-CD 20 antibody drug conjugate, and in the description it is mentioned that the conjugate can be used in combination with doxorubicin, cyclophosphamide, taxanes, capecitabine, gemcitabine, irinotecan, oxaliplatin, prednisone, vincristine, etc., or a combination thereof, while the applicant of the present invention discloses an anti-CD 20 antibody drug conjugate and a preparation thereof, respectively, in the previous applications CN108452318A and CN108452319a, and in the description it is mentioned that the anti-CD 20 antibody drug conjugate can be used in combination with cyclophosphamide, doxorubicin, vincristine, prednisone, a PD1 antibody, CTLA4 inhibitor, or a combination thereof. However, the above patent application simply lists the combination of anti-CD 20 conjugate and clinically commonly used anti-tumor drugs, in the examples, specific drug combination schemes are not designed for the treatment of non-hodgkin lymphoma and curative effect and safety data are obtained, and the above mentioned drugs such as the taxane, the PD1 antibody, the CTLA4 inhibitor and the like which are combined with the anti-CD 20 antibody drug conjugate are not even clinically used for the treatment of non-hodgkin lymphoma, and the various drugs listed in the above patent are only one way of patent writing, which is disclosed accidentally. The above patent application cannot give technical implications of specific drug combination schemes because of uncertainty in the types of available combination drugs, combination schemes, combination effects of the combination drugs and toxicity superposition of the combination drugs. First line standard treatment regimens for DLBCL recommended by the current clinical oncology institute (CSCO) lymphoma clinical guidelines 2022 edition are shown in table a below, including R-CHOP regimens, R-CHOEP regimens, R-miniCHOP regimens, DA-EPOCH-R regimens, and Pola-R-CHP regimens, etc., with rituximab (R), cyclophosphamide (C), vincristine (H), doxorubicin (O), and prednisone (P) in combination, with rituximab (R), cyclophosphamide (C), vincristine (H), doxorubicin (O), etoposide (E), and prednisone (P) in combination, with R-miniCHOP regimens of rituximab (R), cyclophosphamide (C), vincristine (H), doxorubicin (O), and prednisone (P) in combination, wherein CHOP employs low doses, with etoposide (E), doxorubicin (P), doxorubicin (O), cyclophosphamide (C), and prednisone (P), with DA-epothilone (E), etoposide (E), and prednisone (P) in combination, with d 24-35 b, and with d-35 d chemotherapy for each patient, with d's target after chemotherapy, the target cycles of the following the chemotherapy) Rituximab (R), cyclophosphamide (C), vincristine (H), and prednisone (P) in combination. Table a DLBCL first line treatment regimen Although patients are relieved to varying degrees by