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EP-4735038-A1 - ONCOLOGY COMBINATION THERAPY AND METHODS OF USE

EP4735038A1EP 4735038 A1EP4735038 A1EP 4735038A1EP-4735038-A1

Abstract

Disclosed herein is the treatment of cancer by administering plinabulin in combination with an immune checkpoint inhibitor.

Inventors

  • HUANG, LAN
  • LU, YINGJUAN, JUNE

Assignees

  • Beyondspring Pharmaceuticals, Inc.

Dates

Publication Date
20260506
Application Date
20240625

Claims (20)

  1. 1. A method of treating cancer in a subject, the method comprising a treatment cycle comprising the steps of: (i) administering one or more immune checkpoint inhibitor to the subject; (ii) administering plinabulin or a pharmaceutically acceptable salt thereof to the subject; (iii) obtaining a biological sample from the subject; and (iv) determining the levels of one or more biomarkers or levels of one or more cells in the biological sample.
  2. 2. The method of Claim 1, wherein treatment with the one or more immune checkpoint inhibitor and plinabulin is discontinued if the level of the one or more biomarker or one or more cells in the biological sample is above or below a predetermined threshold level, or if a score determined by mathematically combining levels of two or more biomarkers or two or more cells is above or below a predetermined threshold value.
  3. 3. The method of Claim 1 or 2, wherein the one or more biomarker is CCR7, CD40, CD80, CD83, CD86, GEF-H1, IL-2, IFNy, IL-6, IL-12p70, IL-12p40, IL-13, IL-17A, IL-23, G-CSF, PD-L1, IL-8 and IFN- , or a combination thereof.
  4. 4. The method of Claim 3, wherein the one or more biomarker includes CCR7.
  5. 5. The method of Claim 3 or 4, wherein the one or more biomarker includes CD40.
  6. 6. The method of any one of Claims 3 to 5, wherein the one or more biomarker includes CD80.
  7. 7. The method of any one of Claims 3 to 6, wherein the one or more biomarker includes CD83.
  8. 8. The method of any one of Claims 3 to 7, wherein the one or more biomarker includes CD86.
  9. 9. The method of any one of Claims 3 to 7, wherein the one or more biomarker includes GEF-H1.
  10. 10. The method of any one of Claims 1 to 9, wherein the one or more immune checkpoint inhibitor is pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, pidilizumab, ipilimumab, BMS 936559, durvalumab, camrelizumab, dostarlimab, tislelizumab, sintilimab, toripalimab, or a combination thereof.
  11. 11 . The method of Claim 10, wherein the one or more immune checkpoint inhibitor is avclumab.
  12. 12. The method of Claim 10, wherein the one or more immune checkpoint inhibitor is atezolizumab.
  13. 13. The method of Claim 10, wherein the one or more immune checkpoint inhibitor is durvalumab.
  14. 14. The method of Claim 10, wherein the one or more immune checkpoint inhibitor is nivolumab.
  15. 15. The method of Claim 10, wherein the one or more immune checkpoint inhibitor is pembrolizumab.
  16. 16. The method of any one of Claims 1 to 15, wherein the treatment cycle is 21 days.
  17. 17. The method of any one of Claims 1 to 15, wherein the treatment cycle is 28 days.
  18. 18. The method of any one of Claims 1 to 17, wherein the one or more immune checkpoint inhibitor is administered intravenously.
  19. 19. The method of any one of Claims 1 to 18, wherein the one or more immune checkpoint inhibitor is administered on day 1 of the treatment cycle.
  20. 20. The method of any one of Claims 1 to 19, wherein the one or more immune checkpoint inhibitor is administered on day 15 of the treatment cycle.

Description

ONCOLOGY COMBINATION THERAPY AND METHODS OF USE CROSS REFERENCE TO RELATED APPLIATIONS [0001] This patent application claims the benefit of priority to U.S. Provisional Application No. 63/523,609, filed June 27, 2023, U.S. Provisional Application No. 63/589,579, filed October 11, 2023, and U.S. Provisional Application No. 63/631,251, filed April 8, 2024. All of the foregoing applications are fully incorporated herein by reference in their entireties for all purposes. BACKGROUND Field [0002] The present disclosure relates to the field of chemistry and medicine. More specifically, it relates to combination therapies comprising plinabulin, an immune checkpoint inhibitor and radiation therapy for the treatment of cancer. Description of the Related Art [0003] Human cancers harbor numerous genetic and epigenetic alterations, generating neoantigens potentially recognizable by the immune system (Sjoblom et al, 2006). The adaptive immune system, comprised of T and B lymphocytes, has powerful anti-cancer potential, with a broad capacity and exquisite specificity to respond to diverse tumor antigens. [0004] Recent cancer immunotherapy research has focused substantial effort on approaches that enhance anti-tumor immunity by mediating an adaptive immune response to relevant antigens, providing specific immune- stimulatory agents such as immune checkpoint inhibitors. While cancer remains as an incurable disease for the great majority of patients, there exists a particular need for developing effective therapeutic agents and treatment regimens that can be used in cancer therapy. Patients receiving immune checkpoint inhibitors may initially respond to these checkpoint inhibitors, but at a later time become unresponsive (resistant) to these checkpoint inhibitors, or may not respond to these checkpoint inhibitors from the start of their administration (non-responders). SUMMARY [0005] In a first aspect of the present disclosure, provided herein is a method of treating cancer in a subject, the method comprising a treatment cycle comprising the steps of: (i) administering one or more immune checkpoint inhibitor to the subject; (ii) administering plinabulin or a pharmaceutically acceptable salt thereof to the subject; (iii) obtaining a biological sample from the subject; and (iv) determining the levels of one or more biomarkers or levels of one or more cells in the biological sample. [0006] In some embodiments of the first aspect, treatment with the one or more immune checkpoint inhibitor and plinabulin may be discontinued if the level of the one or more biomarker or one or more cells in the biological sample is above or below a predetermined threshold level, or if a score determined by mathematically combining levels of two or more biomarkers or two or more cells is above or below a predetermined threshold value. [0007] In some embodiments of the first aspect, the one or more biomarker is CCR7, CD40, CD80, CD83, CD86, GEF-H1, IL-2, IFNy, IL-6, IL-12p70, IL-12p40, IL-13, IL-17A, IL-23, G-CSF, PD-L1, IL-8 and IFN-0, or a combination thereof. In some embodiments, the one or more biomarker includes CCR7. In some embodiments, the one or more biomarker includes CD40. In some embodiments, the one or more biomarker includes CD80. In some embodiments, the one or more biomarker includes CD83. In some embodiments, the one or more biomarker includes CD86. In some embodiments, the one or more biomarker includes GEF-H1. [0008] In some embodiments of the first aspect, the one or more immune checkpoint inhibitor is pembrolizumab, nivolumab, cemiplimab, atezolizumab, avelumab, pidilizumab, ipilimumab, BMS 936559, durvalumab, camrelizumab, dostarlimab, tislelizumab, sintilimab, toripalimab, or a combination thereof. In some embodiments, the one or more immune checkpoint inhibitor is avelumab. In other embodiments, the one or more immune checkpoint inhibitor is atezolizumab. In yet other embodiments, the one or more immune checkpoint inhibitor is durvalumab. In still yet other embodiments, the one or more immune checkpoint inhibitor is nivolumab. In some embodiments, the one or more immune checkpoint inhibitor is pembrolizumab. In some embodiments, the one or more immune checkpoint inhibitor is camrelizumab. In some embodiments, the one or more immune checkpoint inhibitor is dostarlimab. In some embodiments, the one or more immune checkpoint inhibitor is tislclizumab. In some embodiments, the one or more immune checkpoint inhibitor is sintilimab. In some embodiments, the one or more immune checkpoint inhibitor is toripalimab. [0009] In some embodiments of the first aspect, wherein the treatment cycle is 21 days. In other embodiments, the treatment cycle is 28 days. [0010] In some embodiments of the first aspect, the one or more immune checkpoint inhibitor may be administered intravenously. [0011] In some embodiments of the first aspect, the one or more immune checkpoint inhibitor is administered on day 1 of the treatment cycle. In other embo