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US-20260125486-A1 - METHODS AND COMPOSITIONS FOR CANCER TREATMENT

US20260125486A1US 20260125486 A1US20260125486 A1US 20260125486A1US-20260125486-A1

Abstract

The present application provides methods of treatment of cancers, such as multiple myelomas, with anti-fragment crystallizable receptor-like 5 (FcRH5)/anti-cluster of differentiation 3 (CD3) bispecific antibodies and anti-B cell maturation factor (BCMA)/anti-CD3 bispecific antibodies.

Inventors

  • Erica Ehrha PARK
  • Monica Etelina SUSILO
  • James Niall COOPER
  • Mohamed ELMELIEGY
  • Gregory Joseph FINN

Assignees

  • GENENTECH, INC.
  • PFIZER INC.

Dates

Publication Date
20260507
Application Date
20251219

Claims (20)

  1. 1 . A method of treating a subject having a multiple myeloma (MM), the method comprising administering to the subject (i) an effective amount of a first bispecific antibody that specifically binds to fragment crystallizable receptor-like 5 (FcRH5) and cluster of differentiation 3 (CD3) and (ii) an effective amount of a second bispecific antibody that specifically binds to B-cell maturation antigen (BCMA) and CD3.
  2. 2 . The method of claim 1 , wherein the subject has relapsed or refractory (R/R) MM.
  3. 3 . The method of claim 2 , wherein the subject has diagnosis of R/R MM according to International Myeloma Working Group (IMWG) criteria.
  4. 4 . The method of any one of claims 1-3 , wherein the first bispecific antibody and the second bispecific antibody are administered to the subject in a dosing regimen comprising: (i) a first phase comprising one or more dosing cycles; (ii) a second phase comprising one or more dosing cycles; and, optionally, (iii) a third phase comprising one or more dosing cycles.
  5. 5 . The method of claim 4 , wherein the dosing regimen comprises the first phase and the second phase but does not comprise the third phase.
  6. 6 . The method of claim 4 , wherein the dosing regimen comprises the first phase, the second phase, and the third phase.
  7. 7 . The method of claim 4 or 6 , wherein each dosing cycle of the first phase, the second phase, and/or the third phase is a 14-day dosing cycle.
  8. 8 . The method of any one of claims 4-7 , further comprising a pre-phase, prior to the first phase, comprising one or more dosing cycles.
  9. 9 . The method of claim 8 , wherein the pre-phase comprises one dosing cycle (C1).
  10. 10 . The method of claim 9 , wherein the C1 of the pre-phase is: (i) approximately a 15-day dosing cycle; or (ii) approximately a 22-day dosing cycle.
  11. 11 . The method of claim 10 , wherein the C1 of the pre-phase is approximately a 15-day dosing cycle.
  12. 12 . The method of claim 11 , wherein the pre-phase comprises administering the first bispecific antibody to the subject on Day 9, Day 10, or Day 11 of the C1.
  13. 13 . The method of claim 12 , wherein the first bispecific antibody is administered to the subject on Day 9, Day 10, or Day 11 of the C1 at a step-up dose of 3.6 mg.
  14. 14 . The method of any one of claims 11-13 , wherein the pre-phase comprises administering the second bispecific antibody to the subject on (i) Day 1; (ii) Day 3, Day 4, or Day 5; and (iii) Day 8.
  15. 15 . The method of claim 14 , wherein the second bispecific antibody is administered to the subject on Day 1 at a first step-up dose of 12 mg.
  16. 16 . The method of claim 14 or 15 , wherein the second bispecific antibody is administered to the subject on Day 3, Day 4, or Day 5 at a second step-up dose of 32 mg.
  17. 17 . The method of any one of claims 14-16 , wherein the second bispecific antibody is administered to the subject on Day 8 at a target dose of 76 mg.
  18. 18 . The method of claim 10 , wherein the C1 of the pre-phase is approximately a 22-day dosing cycle.
  19. 19 . The method of claim 18 , wherein the pre-phase comprises administering the first bispecific antibody to the subject on Day 16, Day 17, or Day 18 of the C1.
  20. 20 . The method of claim 19 , wherein the first bispecific antibody is administered to the subject on Day 16, Day 17, or Day 18 of the C1 at a step-up dose of 3.6 mg.

Description

This application is a continuation of International Application No. PCT/US2024/034915, filed on Jun. 21, 2024, which claims priority to U.S. Provisional Patent Application No. 63/509,612, filed on Jun. 22, 2023, and to U.S. Provisional Patent Application No. 63/600,286, filed on Nov. 17, 2023, the entire contents of which are incorporated herein by reference. SEQUENCE LISTING The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on Dec. 15, 2025, is named “00B206_1694.xml” and is 65,974 bytes in size. FIELD OF THE INVENTION The present application relates to the treatment of cancers, such as B cell proliferative disorders. More specifically, the application concerns the treatment of human subjects having multiple myeloma (MM) using an anti-fragment crystallizable receptor-like 5 (FcRH5)/anti-cluster of differentiation 3 (CD3) bispecific antibody and an anti-B-cell maturation antigen (BCMA)/anti-CD3 bispecific antibody. BACKGROUND Cancer remains one of the deadliest threats to human health. In the U.S., cancer affects more than 1.7 million new patients each year and is the second leading cause of death after heart disease, accounting for approximately one in four deaths. Hematologic cancers, in particular, are the second leading cause of cancer-related deaths. Hematologic cancers include multiple myeloma (MM), an incurable neoplasm characterized by the proliferation and accumulation of malignant plasma cells in the bone marrow that leads to the overproduction of monoclonal proteins (M-proteins) detectable in the blood or urine of most patients. A diagnosis of MM affects approximately 30,000 people every year in the United States, and approximately 160,000 people are diagnosed with MM annually worldwide. End-organ damage resulting from MM includes hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM remains incurable despite advances in treatment, with an estimated median survival of 8-10 years for standard-risk and 2-3 years for high-risk myeloma, even with aggressive treatments such as autologous stem cell transplantation (SCT). Despite the significant improvement in patient survival over the past 20 years, only 10-15% of patients achieve or exceed expected survival compared with the matched general population. Therefore, there is a need for improved treatment regimens for MM and other cancers (e.g., hematologic cancers). SUMMARY OF THE INVENTION Provided herein are, inter alia, methods of treating a subject having a cancer (e.g., MM), compositions for use, and related articles of manufacture. In one aspect, provided herein is a method of treating a subject having a multiple myeloma (MM), the method including administering to the subject (i) an effective amount of a first bispecific antibody that specifically binds to fragment crystallizable receptor-like 5 (FcRH5) and cluster of differentiation 3 (CD3) and (ii) an effective amount of a second bispecific antibody that specifically binds to B-cell maturation antigen (BCMA) and CD3. In another aspect, provided herein is a bispecific antibody that specifically binds to FcRH5 and CD3 for use in treatment of a subject having an MM, the treatment comprising administration of a first bispecific antibody that specifically binds to FcRH5 and CD3 and a second bispecific antibody that specifically binds to BCMA and CD3 to the subject. In another aspect, provided herein is a bispecific antibody that specifically binds to BCMA and CD3 for use in treatment of a subject having an MM, the treatment comprising administration of a first bispecific antibody that specifically binds to FcRH5 and CD3 and a second bispecific antibody that specifically binds to BCMA and CD3 to the subject. In some aspects, the subject has relapsed or refractory (R/R) MM. In some aspects, the subject has diagnosis of R/R MM according to International Myeloma Working Group (IMWG) criteria. In some aspects, the first bispecific antibody and the second bispecific antibody are administered to the subject in a dosing regimen including: (i) a first phase including one or more dosing cycles; (ii) a second phase including one or more dosing cycles; and, optionally, (iii) a third phase including one or more dosing cycles. In some aspects, the dosing regimen includes the first phase and the second phase but does not include the third phase. In some aspects, the dosing regimen includes the first phase, the second phase, and the third phase. In some aspects, each dosing cycle of the first phase, the second phase, and/or the third phase is a 14-day dosing cycle. In some aspects, the second phase is a 28-day dosing cycle. In some aspects, the second bispecific antibody is administered to the subject on Day 1 of each dosing cycle of the second phase at a target dose of 76 mg. In some aspects, the first phase includes dosing cycles C1 to C26, and the second phase com