PKS-island positive E. coli as marker of negative response to anti-PD1 therapy in colorectal cancer

Patent metadata

Field	Value
Publication number	US-12435378-B2
Application number	US-201917299428-A
Country	US
Kind code	B2
Filing date	Dec 10, 2019
Priority date	Dec 11, 2018
Publication date	Oct 7, 2025
Grant date	Oct 7, 2025

Abstract

A method of predicting resistance to anti-PD1 therapy in a subject suffering from cancer comprising the steps of a) determining, from a biological sample from a subject, in particular a feces or colonic biopsy sample from the subject, the presence of a bacterial pks island, b) predicting from the result of step a) that the subject is likely to be resistant to anti-PD1 therapy, is provided. Methods of treating cancer in a subject by assessing the presence or absence of bacterial pks island in a biological sample from a subject, in particular a feces or colonic biopsy sample from the subject and administering to the subject an anti-cancer therapy are also provided.

First claim

The invention claimed is:

1. A method for treating a subject suffering from colorectal cancer, said method comprising
i) determining the presence or absence of an E. coli pks island in a feces or colonic biopsy sample from said subject; and
ii) administering to said subject a therapeutically effective amount of an anti-cancer therapy,

wherein:
the anti-cancer therapy administered to said subject is not an anti-PD1 therapy when a pks island has been determined to be present in feces or a colonic biopsy sample from said subject, or
the anti-cancer therapy administered to said subject is an anti-PD1 antibody and/or anti-PDL1 antibody when a pks island has been determined to be absent in feces or a colonic biopsy sample from said subject.

2. The method according to claim 1 , wherein said anti-PD1 antibody is cemiplimab.

3. The method according to claim 1 , wherein said anti-PD1 antibody and/or anti-PDL1 antibody is used in combination with an additional anti-cancer therapy.

4. The method according to claim 3 , wherein the additional anti-cancer therapy is selected from the group consisting of an immune checkpoint inhibitor, radiation therapy, surgery, a small molecule kinase inhibitor, a chemotherapeutic agents, a nucleic acid synthesis inhibitor, a cancer vaccine, an anti-CD38 antibody, an anti-MUC16×CD3 bispecific antibody, an anti-CD20×CD3 bispecific antibody, a granulocyte-macrophage colony-stimulating factor (GM-CSF), an anti-TGFβ antibody, an indoleamine-2,3-dioxygenase (IDO) inhibitor, an IL-6R inhibitor, an IL-4R inhibitor, an IL-10 inhibitor, a cytokine, an anti-inflammatory drug, a corticosteroids, a non-steroidal anti-inflammatory drug, and combinations thereof.

5. The method according to claim 1 , wherein said anti-cancer therapy which is not an anti-PD1 therapy is selected from the group consisting of irinotecan, oxaliplatin, combination of irinotecan with 5-FU and leucovorin, combination of oxaliplatin with 5-FU and leucovorin, combination of irinotecan with capecitabine, combination of oxaliplatin and capecitabine, anti-EGFR antibodies, anti-VEGFR antibodies, and anti-VEGFR2 antibodies.

6. The method according to claim 5 , wherein said anti-EGFR antibodies are selected from the group consisting of cetuximab and panitumumab.

7. The method according to claim 5 , wherein said anti-VEGFR antibody is bevacizumab.

8. The method according to claim 5 , wherein said anti-VEGFR2 antibody is ramucirumab.

9. The method according to claim 1 , wherein the presence of the pks island is determined by isolation of Escherichia coli bacteria on agar and determination of the presence of a pks island DNA.

10. The method according to claim 1 , wherein the presence of the pks island is determined by determining the presence of an Escherichia coli -specific DNA and determining the presence of a pks island DNA.

11. The method according to claim 1 , wherein the presence of a pks island is determined by determining the presence of a pks island DNA.

12. The method according to claim 11 , wherein the presence of a pks island DNA is determined by PCR.

13. The method according to claim 12 , wherein the PCR is performed using primers specific for a gene selected from the group consisting of the ClbH, ClbJ, ClbN, ClbC, ClbI, ClbOn ClbB and ClbK genes of the pks island.

Assignees

• Sanofi Sa
• Univ Clermont Auvergne
• Sanifi

Inventors

• Billard Elisabeth
• Bonnet Mathilde
• Dumas Bruno
• Lopes Amélie

Classifications

• C12Q2600/106

  Pharmacogenomics, i.e. genetic variability in individual responses to drugs and drug metabolism · CPC title

• A61K2039/507

  Comprising a combination of two or more separate antibodies · CPC title

• A61K2039/505

  comprising antibodies · CPC title

• A61K39/39558

  against tumor tissues, cells, antigens · CPC title

• C07K2317/76

  Antagonist effect on antigen, e.g. neutralization or inhibition of binding · CPC title