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WO-2026096660-A1 - PLK1 INHIBITOR IN COMBINATION WITH ANTI-ANGIOGENICS FOR TREATING METASTATIC CANCER

WO2026096660A1WO 2026096660 A1WO2026096660 A1WO 2026096660A1WO-2026096660-A1

Abstract

Provided include methods, compositions and kits for treating metastatic cancer in a subject. The method can comprise administering to a metastatic colorectal cancer patient an effective amount of a PLK1 inhibitor (for example, onvansertib) and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of the PLK1 inhibitor and bevacizumab in a manner sufficient to reduce or inhibit progression of the metastatic cancer.

Inventors

  • RIDINGER, Maya
  • SMEAL, TOD
  • ERLANDER, MARK

Assignees

  • CARDIFF ONCOLOGY, INC.

Dates

Publication Date
20260507
Application Date
20251029
Priority Date
20241030

Claims (20)

  1. 1. A method of treating a metastatic colorectal cancer, comprising: administering to a patient with a metastatic colorectal cancer (mCRC) an effective amount of onvansertib and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of onvansertib and bevacizumab.
  2. 2. The method of claim 1, wherein the patient has not received any treatment comprising bevacizumab within about three months or about four months prior to the administration of onvansertib and bevacizumab.
  3. 3. The method of claim 1, wherein the patient has not received any treatment comprising bevacizumab within about three months or about twelve months prior to the administration of onvansertib and bevacizumab.
  4. 4. The method of claim 1, wherein the patient has received at least one treatment comprising bevacizumab more than three months prior to the administration of onvansertib and bevacizumab.
  5. 5. The method of any one of claims 1-4, wherein the patient has received at least one treatment not comprising bevacizumab.
  6. 6. The method of claim 5, wherein the at least one treatment not comprising bevacizumab occurs within about three months prior to the administration of onvansertib and bevacizumab.
  7. 7. The method of any one of claims 1-6, further comprising, at least three months after the administration of onvansertib and bevacizumab has ended, administrating at least one additional treatment comprising bevacizumab to the patient.
  8. 8. The method of claim 7, wherein the at least one additional treatment comprising bevacizumab and onvansertib.
  9. 9. The method of claim 7 or 8, wherein any two additional treatments comprising bevacizumab are separated by a time period of at least three months.
  10. 10. The method of any one of claims 1-9, wherein the patient has not received any treatment comprising bevacizumab and a chemotherapy containing fluorouracil within at least three months prior to the administration of onvansertib and bevacizumab.
  11. 11. The method of any one of claims 1-10, wherein the metastatic colorectal cancer is a mutated metastatic colorectal cancer having one or more mutations in the RAS gene.
  12. 12. The method of claim 11, wherein the metastatic colorectal cancer is KRAS- mutated metastatic colorectal cancer, NRAS-mutated metastatic colorectal cancer, HRAS- mutated metastatic colorectal cancer, or a combination thereof.
  13. 13. The method of any one of claims 1-12, wherein administration of onvansertib and bevacizumab is performed in combination with a chemotherapy containing fluorouracil.
  14. 14. The method of claim 13, wherein the chemotherapy containing fluorouracil is FOLFOX, FOLFIRI, 5-fluorouuracil (5-FU), FOLFIRINOX, FOLFOXIRI, or a combination thereof.
  15. 15. The method of any one of claim 1-14, wherein the administration comprises at least two treatment cycles of the administration of onvansertib and bevacizumab, and optionally wherein two of the treatment cycles are in consecutive.
  16. 16. The method of claim 15, wherein onvansertib is administered on at least four days in a treatment cycle and bevacizumab is administered once every week or two weeks during a treatment cycle.
  17. 17. The method of any one of claims 15-16, wherein a treatment cycle is about 21 to 28 days.
  18. 18. The method of any one of claims 1-17, wherein onvansertib and bevacizumab are administered to the patient simultaneously, separately, or sequentially.
  19. 19. The method of any one of claims 1-18, wherein the administration of onvansertib is oral administration, and the administration of bevacizumab is intravenous administration.
  20. 20. The method of any one of claims 1-19, wherein onvansertib is administered at 12 mg/m 2 -90 mg/m 2 , optionally at 15 mg/m 2 -30 mg/m 2 .

Description

53NC-830006-WO PATENT PLK1 INHIBITOR IN COMBINATION WITH ANTI-ANGIOGENICS FOR TREATING METASTATIC CANCER RELATED APPLICATIONS [0001] This application claims the benefit under 35 U.S.C. § 119(e) ofU.S. Provisional Patent Application Ser. No. 63/714,066, filed October 30, 2024, U.S. Provisional Patent Application Ser. No. 63/741,728, filed January 3, 2025, and U.S. Provisional Patent Application Ser. No. 63/778,966, filed March 27, 2025. The content of each of these related applications is incorporated herein by reference in its entirety for all purposes. BACKGROUND Field [0002] The present disclosure relates generally to the field of treatment for cancer. Description of the Related Art [0003] The Polo-like kinase 1 (PLK1) is a serine/threonine kinase and the most well characterized member of this family of 5 closely related regulatory proteins. PLK-1 is a master regulator of mitosis via its control of the entry and progression of cells into and through mitosis. PLK1 performs several important functions throughout mitotic (M) phase of the cell cycle, including the regulation of centrosome maturation and spindle assembly, the removal of cohesins from chromosome arms, the inactivation of anaphase-promoting complex/cyclosome (APC/C) inhibitors, and the regulation of mitotic exit and cytokinesis. PLK1 plays a key role in centrosome functions and the assembly of bipolar spindles. PLK1 controls kinetochore interactions with the spindle microtubules that is required for successful separation and segregation chromatids to the appropriate mother and daughter cells. PLK1 also acts as a negative regulator of p53 family members leading to ubiquitination and subsequent degradation of p53/TP53, inhibition of the p73/TP73 mediated pro-apoptotic functions and phosphorylation/degradation of bora, a cofactor of Aurora kinase A. During the various stages of mitosis PLK1 localizes to the centrosomes, kinetochores and central spindle. PLK1 is aberrantly overexpressed in a variety of human cancers and is correlated with cellular proliferation and poor prognosis. [0004] The most advanced stage of cancer is stage IV, which is defined by the cancer spreading to distant parts of the body from where the cancer first originated (e.g., metastasis). Angiogenesis is necessary for metastasis to occur and several anti-angiogenics have been approved for use in humans to treat metastatic cancers. However, according to the Centers for Disease Control and Prevention, about one in every five deaths in the United States is still due to cancer. There is still a need for more effective treatments for advanced (e.g., metastatic) cancers. SUMMARY [0005] Disclosed herein include methods of treating cancer, including a metastatic cancer. Provided herein includes a method of treating a metastatic colorectal cancer, comprising: administering to a patient with a metastatic colorectal cancer (mCRC) an effective amount of onvansertib and an effective amount of bevacizumab, wherein the patient has not received any treatment comprising bevacizumab within at least three months prior to the administration of onvansertib and bevacizumab. In some embodiments, the patient has not received any treatment comprising bevacizumab within about three months or about four months prior to the administration of onvansertib and bevacizumab. In some embodiments, the patient has not received any treatment comprising bevacizumab within about three months or about twelve months prior to the administration of onvansertib and bevacizumab. In some embodiments, the patient has received at least one treatment comprising bevacizumab more than three months prior to the administration of onvansertib and bevacizumab. In some embodiments, the patient has received at least one treatment (e.g., a cancer treatment) not comprising bevacizumab. In some embodiments, the at least one treatment not comprising bevacizumab occurs within about three months prior to the administration of onvansertib and bevacizumab. [0006] The method can, for example, further comprise at least three months after the administration of onvansertib and bevacizumab has ended, administrating at least one additional treatment comprising bevacizumab to the patient. The at least one additional treatment can comprise bevacizumab and onvansertib. In some embodiments, any two additional treatments comprising bevacizumab are separated by a time period of at least three months. In some embodiments, the patient has not received any treatment comprising bevacizumab and a chemotherapy containing fluorouracil within at least three months prior to the administration of onvansertib and bevacizumab. The metastatic colorectal cancer can be, for example, a mutated metastatic colorectal cancer having one or more mutations in the RAS gene. In some embodiments, the metastatic colorectal cancer is KRAS-mutated metastatic colorectal cancer, NRAS-mutated metastatic colorectal cancer, HRAS-mutated metastatic colorectal cancer, or a combination