Search

KR-20260065881-A - Dynamic protein signatures for predicting non-response to immune checkpoint inhibitor therapy

KR20260065881AKR 20260065881 AKR20260065881 AKR 20260065881AKR-20260065881-A

Abstract

The present disclosure provides a method for identifying a subject with cancer who does not respond to or is likely not to respond to treatment (e.g., immune checkpoint inhibitor monotherapy), wherein the cancer exhibits altered (e.g., increased or decreased) expression levels of a biomarker panel, and a method for providing additional cancer treatment to the subject with said cancer using said method.

Inventors

  • 오헤이건 로넌
  • 친 린다

Assignees

  • 애프리시티 헬스, 인코포레이티드

Dates

Publication Date
20260511
Application Date
20240830
Priority Date
20230901

Claims (20)

  1. A method for treating cancer in a subject by providing one or more additional therapies to the subject having said cancer, wherein the method comprises: (i) a step of determining the amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is before the administration of immune checkpoint inhibitor monotherapy and at least one subsequent time point is from about 3 weeks to about 6 months after the administration of the immune checkpoint inhibitor, and the biomarker panel comprises one or more of CA6, CDNF, MIA, MYOC, NEFL, and TCL1B; (ii) a step of determining a non-response score by comparing the amount or level of the biomarker panel from two or more different time points, wherein the non-response score indicates that the subject is unlikely to respond to the immune checkpoint inhibitor monotherapy; and (iii) a method comprising the step of treating cancer in a subject by administering one or more additional therapies to a subject determined to have the above non-response score.
  2. In paragraph 1, one or more additional therapies are selected from surgery, radiation therapy, chemotherapy, immunotherapy, endocrine therapy, cryotherapy, and corticosteroids.
  3. A method for identifying a subject with cancer who is likely not to respond to immune checkpoint inhibitor monotherapy administered to the subject, the method comprises: (i) a step of providing an amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is a time point prior to administration of immune checkpoint inhibitor monotherapy, and at least one subsequent time point is a time point from about 3 weeks to about 6 months after administration of the immune checkpoint inhibitor, and the biomarker panel comprises one or more of CA6, CDNF, MIA, MYOC, NEFL, and TCL1B; (ii) a step of determining a non-response score by comparing the amount or level of the panel of biological markers from two or more different time points, wherein the non-response score indicates that the subject is unlikely to respond to the immune checkpoint inhibitor monotherapy, thereby identifying a subject likely not to respond to the immune checkpoint inhibitor monotherapy.
  4. A method according to any one of claims 1 to 3, wherein the immune checkpoint inhibitor monotherapy targets PD-1, PD-L1, CTLA4, LAG3, or any combination thereof.
  5. A method according to any one of paragraphs 1 to 4, wherein the immune checkpoint inhibitor monotherapy is an antibody therapy.
  6. In paragraph 5, the antibody is ipilimumab, nivolumab, lilatlimab, pembrolizumab, atezolizumab, durvalumab, avelumab, cemiplimab, or dostalimab.
  7. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises CA6, CDNF, MIA, MYOC, NEFL, and TCL1B.
  8. In any one of claims 1 to 6, the biomarker panel is ADAM22, ADAMTS8, AMTS8, ANGPT2, AOC1, BCL2L11, BMP4, BRK1, CA6, CCL13, CCL25, CD14, CD34, CDH17, CDNF, CERT, CES3, CLEC4A, CPVL, CSF3, CTSF, CTSL, DKK4, ECE1, ENG, FBP1, FRZB, GBP2, GFBP2, GLT8D2, GPR37, HGF, HMBS, IGFBP2, IL5, IL6, ITGB6, ITM2A, KRT5, LILRB4, MIA, MMP13, MMP3, MMP8, MYOC, NEFL, NID1, NOS3, NRP1, PAEP, PAPPA, PRTG, PSPN, PTGDS, SFTPD, A method comprising one or more of SMOC1, TCL1A, TCL1B, TCN2, TDGF1, TFPI, TGREM2, TINAGL1, TNC, TNFRSF10B, TNFSF14, VASN, and WARS.
  9. In any one of claims 1 to 6, the biomarker panel is ADAM22, ADAMTS8, AMTS8, ANGPT2, AOC1, BCL2L11, BMP4, BRK1, CA6, CCL13, CCL25, CD14, CD34, CDH17, CDNF, CERT, CES3, CLEC4A, CPVL, CSF3, CTSF, CTSL, DKK4, ECE1, ENG, FBP1, FRZB, GBP2, GFBP2, GLT8D2, GPR37, HGF, HMBS, IGFBP2, IL5, IL6, ITGB6, ITM2A, KRT5, LILRB4, MIA, MMP13, MMP3, MMP8, MYOC, NEFL, NID1, NOS3, NRP1, PAEP, PAPPA, PRTG, PSPN, PTGDS, SFTPD, A method comprising at least 6 of SMOC1, TCL1A, TCL1B, TCN2, TDGF1, TFPI, TGREM2, TINAGL1, TNC, TNFRSF10B, TNFSF14, VASN, and WARS.
  10. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises one or more of ADAM22, BMP4, CA6, CCL25, CDH17, CDNF, CES3, GBP2, HGF, HMBS, IL5, IL6, ITGB6, KRT5, MIA, MMP13, MMP3, MYOC, NEFL, NID1, NRP1, PAEP, PTGDS, SFTPD, SMOC1, TCL1B, TGREM2, TNC, TNFRSF10B, TNFSF14, and VASN.
  11. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises at least 6 of ADAM22, BMP4, CA6, CCL25, CDH17, CDNF, CES3, GBP2, HGF, HMBS, IL5, IL6, ITGB6, KRT5, MIA, MMP13, MMP3, MYOC, NEFL, NID1, NRP1, PAEP, PTGDS, SFTPD, SMOC1, TCL1B, TGREM2, TNC, TNFRSF10B, TNFSF14, and VASN.
  12. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises one or more of AMTS8, ANGPT2, BCL2L11, BRK1, CA6, CCL13, CD14, CD34, CDNF, CERT, CLEC4A, CPVL, CSF3, CTSF, CTSL, DKK4, ECE1, ENG, FRZB, GFBP2, GLT8D2, ITGB6, LILRB4, MIA, MMP8, MYOC, NEFL, PAEP, PAPPA, PRTG, PSPN, TCL1A, TCL1B, TCN2, TDGF1, TFPI, TINAGL1, and WARS.
  13. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises at least 6 of AMTS8, ANGPT2, BCL2L11, BRK1, CA6, CCL13, CD14, CD34, CDNF, CERT, CLEC4A, CPVL, CSF3, CTSF, CTSL, DKK4, ECE1, ENG, FRZB, GFBP2, GLT8D2, ITGB6, LILRB4, MIA, MMP8, MYOC, NEFL, PAEP, PAPPA, PRTG, PSPN, TCL1A, TCL1B, TCN2, TDGF1, TFPI, TINAGL1, and WARS.
  14. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises one or more of ADAMTS8, ANGPT2, AOC1, BCL2L11, BRK1, CA6, CCL13, CD14, CD34, CDNF, CLEC4A, CPVL, DKK4, ECE1, FBP1, GPR37, IGFBP2, ITM2A, LILRB4, MIA, MMP13, MMP8, MYOC, NEFL, NOS3, PAPPA, PSPN, TCL1A, TCL1B, TCN2, TFPI, TINAGL1, VASN, and WARS.
  15. A method according to any one of claims 1 to 6, wherein the biomarker panel comprises at least 6 of ADAMTS8, ANGPT2, AOC1, BCL2L11, BRK1, CA6, CCL13, CD14, CD34, CDNF, CLEC4A, CPVL, DKK4, ECE1, FBP1, GPR37, IGFBP2, ITM2A, LILRB4, MIA, MMP13, MMP8, MYOC, NEFL, NOS3, PAPPA, PSPN, TCL1A, TCL1B, TCN2, TFPI, TINAGL1, VASN, and WARS.
  16. A method according to any one of claims 1 to 15, wherein the biomarker panel comprises a protein.
  17. A method according to claim 16, wherein step (i) comprises detecting a panel of biomarkers in a biological sample through an enzyme-linked immunosorbent assay (ELISA) or a proximity extension assay (PEA).
  18. A method according to any one of claims 1 to 15, wherein the biomarker panel comprises nucleic acid molecules.
  19. In claim 18, the method comprises step (i) detecting a biomarker panel in a biological sample through nucleic acid hybridization assay, nucleic acid amplification assay, or sequencing.
  20. A method according to any one of claims 1 to 19, wherein the biological sample is a blood sample, a serum sample, or a plasma sample.

Description

Dynamic protein signatures for predicting non-response to immune checkpoint inhibitor therapy Related applications This application claims priority to U.S. Provisional Patent Application No. 63/536,127, filed September 1, 2023. The full contents of said document are incorporated herein by reference. Although significant progress has been made in the types and number of cancer treatments, a large number of patients do not respond to these therapies. It may take at least six months for clinical readings to determine whether a patient responds to treatment. During this period, patients may experience unnecessary financial, social, emotional, and physical hardships if they do not respond. Furthermore, waiting for a determination of the response to cancer treatment delays the administration of additional therapies that could benefit the patient in treating the cancer. In some embodiments, the present disclosure provides a method for providing one or more additional therapies to a subject having cancer in order to treat cancer in the subject, said method: (i) a step of determining the amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is before the administration of immune checkpoint inhibitor monotherapy and at least one subsequent time point is from about 3 weeks to about 6 months after the administration of the immune checkpoint inhibitor, and the biomarker panel comprises one or more of CA6, CDNF, MIA, MYOC, NEFL, and TCL1B; (ii) a step of determining a non-response score by comparing the amount or level of the biomarker panel from two or more different time points, wherein the non-response score indicates, with a diagnostic accuracy (AUC) of at least 0.7, that the subject is unlikely to respond to the immune checkpoint inhibitor monotherapy; and (iii) a step of treating cancer in a subject by administering one or more additional therapies to a subject determined to have the above non-response score. In some embodiments, the present disclosure provides a method for providing one or more additional therapies to a subject having cancer in order to treat cancer in the subject, said method: (i) a step of determining the amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is before the administration of immune checkpoint inhibitor monotherapy and at least one subsequent time point is from about 3 weeks to about 6 months after the administration of the immune checkpoint inhibitor, and the biomarker panel comprises one or more of CA6, CDNF, MIA, MYOC, NEFL, and TCL1B; (ii) a step of determining a non-response score by comparing the amount or level of the biomarker panel from two or more different time points, wherein the non-response score indicates that the subject is unlikely to respond to the immune checkpoint inhibitor monotherapy; and (iii) a step of treating cancer in a subject by administering one or more additional therapies to a subject determined to have the above non-response score. In some embodiments, one or more additional therapies are selected from surgery, radiation therapy, chemotherapy, immunotherapy, endocrine therapy, cryotherapy, and corticosteroids. In some embodiments, the present disclosure provides a method for identifying a subject with cancer who is likely not to respond to an immune checkpoint inhibitor monotherapy administered to the subject, said method comprising: (i) a step of providing an amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is a time point prior to administration of immune checkpoint inhibitor monotherapy, and at least one subsequent time point is a time point from about 3 weeks to about 6 months after administration of the immune checkpoint inhibitor, and the biomarker panel comprises one or more of CA6, CDNF, MIA, MYOC, NEFL, and TCL1B; (ii) a step of determining a non-response score by comparing the amount or level of the panel of biological markers from two or more different time points, wherein the non-response score identifies a subject likely not to respond to the immune checkpoint inhibitor monotherapy by indicating with a diagnostic accuracy (AUC) of at least 0.7 that the subject is unlikely to respond to the immune checkpoint inhibitor monotherapy. In some embodiments, the present disclosure provides a method for identifying a subject with cancer who is likely not to respond to an immune checkpoint inhibitor monotherapy administered to the subject, said method comprising: (i) a step of providing an amount or level of a biomarker panel in a biological sample obtained from the subject at two or more different time points, wherein the first time point is a time point prior to administration of immune checkpoint inhibitor monotherapy, and at least one subsequent