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RU-2025132681-A - Combination therapies including claudin 18.2 antagonists for the treatment of cancer

RU2025132681ARU 2025132681 ARU2025132681 ARU 2025132681ARU-2025132681-A

Inventors

  • Цянь Сюэмин
  • ДЖЕРМА Каролайн
  • ЦИ Чуань
  • Сюй Ли

Assignees

  • Сучжоу трансента терапьютикс Ко., Лтд.
  • ТРАНСЕНТА ХОЛДИНГ ЛИМИТЕД
  • ТРАНСЕНТА ТЕРАПЬЮТИКС, ИНК.

Dates

Publication Date
20260504
Application Date
20240531
Priority Date
20230603

Claims (20)

  1. 1. A method for treating a cancer in which CLDN18.2 (claudin-18 splice variant 2) is expressed in a human subject in need thereof, comprising
  2. administering to the subject a therapeutically effective amount of a CLDN18.2 antagonist in combination with chemotherapy,
  3. where the subject is determined to have a moderate to high or low level of CLDN18.2 expression in a cancer sample (e.g., a tumor tissue sample).
  4. 2. A method for identifying and treating a subject having a cancer disease that expresses claudin 18.2 (CLDN18.2) and that may benefit from treatment comprising a CLDN18.2 antagonist in combination with chemotherapy, wherein the method comprises:
  5. (a) determination of the CLDN18.2 protein level in a cancer sample (e.g., a tumor tissue sample) and
  6. (b) selecting a subject having intermediate to high or low levels of CLDN18.2 protein for treatment.
  7. 3. The method according to claim 1 or 2, wherein the CLDN18.2 protein level or the CLDN18.2 expression level is measured by immunohistochemistry (IHC) analysis, hybridization analysis or amplification analysis.
  8. 4. The method according to any of paragraphs 1-3, where
  9. (1) the CLDN18.2 protein level or CLDN18.2 expression level is quantitatively measured by membrane staining intensity measured by IHC using an anti-CLDN18.2 diagnostic reagent (e.g., an anti-CLDN18.2 diagnostic antibody), and/or
  10. (2) wherein the CLDN18.2 protein level or CLDN18.2 expression level is quantitatively measured by the percentage of cancer cells having a predetermined membrane staining intensity threshold determined by IHC using an anti-CLDN18.2 diagnostic reagent (e.g., an anti-CLDN18.2 diagnostic antibody).
  11. 5. The method according to any of paragraphs 1-4, where
  12. (1)
  13. a) a moderate to high level of CLDN18.2 protein or CLDN18.2 expression corresponds to at least 40% of cancer cells in a cancer sample (e.g., a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 2+ (e.g., 2+ or 3+) when measured using a diagnostic antibody against CLDN18.2, optionally on a Leica Bond III LDT platform, or corresponds to an equivalent value measured on another assay platform, and/or
  14. b) a low level of CLDN18.2 protein or CLDN18.2 expression corresponds to at least 1% (e.g., at least 2%, at least 5%, or at least 10%) of the cancer cells in a cancer sample (e.g., a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 1+, and less than 40% of the cancer cells in a cancer sample (e.g., a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 2+ or 3+ when measured using a diagnostic antibody against CLDN18.2, optionally on a Leica Bond III LDT platform, or corresponds to an equivalent value measured on another assay platform, and/or
  15. (2)
  16. a) a moderate to high level of CLDN18.2 protein or CLDN18.2 expression corresponds to at least 40% of cancer cells in a cancer sample (e.g., a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 2+ (e.g., 2+ or 3+) when measured using 14G11, optionally on a Leica Bond III LDT platform, or corresponds to an equivalent value measured on another assay platform, and/or
  17. b) a low level of CLDN18.2 protein or CLDN18.2 expression corresponds to at least 1% (e.g., at least 2%, at least 5%, or at least 10%) of the cancer cells in a cancer sample (e.g., in a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 1+, and less than 40% of the cancer cells in a cancer sample (e.g., in a tumor tissue sample) having a level of CLDN18.2 expression characterized by a membrane staining intensity of at least 2+ or 3+ when measured using 14G11, optionally on a Leica Bond III LDT platform, or corresponds to an equivalent value measured on another assay platform.
  18. 6. The method according to any of paragraphs 4, 5, where
  19. (1) The diagnostic antibody against CLDN18.2 contains:
  20. (a) the sequences HCDR1 (heavy chain complementarity determining region 1), HCDR2 and HCDR3, and LCDR1 (light chain complementarity determining region 1), LCDR2, and LCDR3, where