System and methods for deriving gene signature biomarkers of response to PD-1 antagonists
AssigneeMerck Sharp & Dohme Corp.
InventorsMark D. Ayers, Andrey Loboda, Jared K. Lunceford, Terrill K. McClanahan, Erin E. Murphy, Michael Nebozhyn
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Abstract
A gene expression platform, which is a combination of a set of genes that are correlated with response to a PD-1 antagonist in multiple tumor types and a normalization gene set, is disclosed. A method and system of using the gene expression platform to derive gene signature biomarkers of anti-tumor response to a PD-1 antagonist and to test patient samples for predictive gene signature biomarkers are also disclosed.
Claims7
A method for treating a patient having a tumor which comprises determining if a sample of the tumor is positive or negative for a gene signature biomarker based on a gene signature score, wherein the gene signature score is calculated based on a combination of gene expression values for all of the genes in the gene signature biomarker, and administering to the patient a PD-1 antagonist if the tumor is positive for the biomarker or administering to the subject a cancer treatment that does not include a PD-1 antagonist if the tumor is negative for the biomarker, wherein the gene signature biomarker is for a gene signature that comprises the 18-Gene Up-Down Signature in Table 2 below:
- TABLE 2
- 18 Gene Up-
- Down
- Signature
- 1
- CCL5
- 2
- CD27
- 3
- CD274
- 4
- CD276
- 5
- CD8A
- 6
- CMKLR1
- 7
- CXCL9
- 8
- CXCR6
- 9
- HLA.DQA1
- 10
- HLA.DRB1
- 11
- HLA.E
- 12
- IDO1
- 13
- LAG3
- 14
- NKG7
- 15
- PDCD1LG2
- 16
- PSMB10
- 17
- STAT1
- 18
- TIGIT
Dependencies are inferred from the claim text.