METHODS OF DETECTING AND TREATING SUBJECTS WITH CHECKPOINT INHIBITOR-RESPONSIVE CANCER
Disclosed herein are methods of detecting and treating checkpoint inhibitor responsive cancers comprising calculating, determining, or obtaining PD-L1 expression, CD8A expression, and tumor content from a cancer specimen.
1 . A method of treatment comprising calculating PD-L1 expression, CD8A expression, and tumor content in a tumor specimen from a subject to identify the subject as having a checkpoint inhibitor responsive cancer; and administering a checkpoint inhibitor therapy to the identified subject.
2 . The method of claim 1 , wherein one or more of the following are also calculated for the tumor specimen: the presence of chimeric transcripts indicative of gene fusion, cDNA sequence data from cDNA converted from mRNA, DNA sequence data, tumor mutation burden (TMB)-associated data, and microsatellite instability (MSI)-associated data.
3 . The method of claim 2 , wherein tumor mutation burden (TMB)-associated data is also calculated for the tumor specimen.
4 . The method of claim 1 , wherein the tumor specimen is a formalin-fixed paraffin-embedded (FFPE) tumor specimen.
5 . (canceled)
6 . (canceled)
7 . The method of claim 1 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the PD-L1 expression is calculated as high, wherein high PD-L1 expression equals at least the 73.3 percentile or more of PD-L1 expression in a population of tumor profiles.
8 . (canceled)
9 . The method of claim 7 , wherein the calculated PD-L1 expression is confirmed with a secondary measurement of PD-L1 expression using a second amplicon, and wherein the secondary measurement's percentile value is 80% or more of the calculated PD-L1 expression value.
10 . (canceled)
11 . The method of claim 1 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the CD8A expression is calculated as high, wherein high CD8A expression equals at least the 67.6 percentile or more of CD8A expression in a population of tumor profiles.
12 . (canceled)
13 . The method of claim 11 , wherein the calculated CD8A expression is confirmed with a secondary measurement of GZMA expression using a second amplicon, and wherein the secondary measurement's percentile value is 80% or more of the calculated CD8A expression value.
14 . The method of claim 1 , wherein the tumor specimen has a tumor content of 40% or more.
15 . The method of claim 1 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the PD-L1 expression is calculated as high, the CD8A expression is calculated as high, and the tumor content of the tumor specimen is 40% or more.
16 . (canceled)
17 . The method of claim 1 , wherein the checkpoint inhibitor is an anti-PD-1 antibody, an anti-CTLA-4 antibody, an anti-PD-L1 antibody, or an anti-PD-L2.
18 . (canceled)
19 . (canceled)
20 . (canceled)
21 . A method of identifying whether a subject has a checkpoint inhibitor responsive cancer comprising calculating PD-L1 expression, CD8A expression, and tumor content in a tumor specimen from a subject to identify whether the subject has a checkpoint inhibitor responsive cancer.
22 . The method of claim 21 , wherein one or more of the following are also calculated for the tumor specimen: the presence of chimeric transcripts indicative of gene fusion, cDNA sequence data from cDNA converted from mRNA, DNA sequence data, tumor mutation burden (TMB)-associated data, and microsatellite instability (MSI)-associated data.
23 . The method of claim 22 , wherein tumor mutation burden (TMB)-associated data is also calculated for the tumor specimen.
24 . The method of claim 21 , wherein the tumor specimen is a formalin-fixed paraffin-embedded (FFPE) tumor specimen.
25 . (canceled)
26 . (canceled)
27 . The method of claim 21 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the PD-L1 expression is calculated as high, wherein high PD-L1 expression equals at least the 73.3 percentile or more of PD-L1 expression in a population of tumor profiles.
28 . (canceled)
29 . The method of claim 27 , wherein the calculated PD-L1 expression is confirmed with a secondary measurement of PD-L1 expression using a second amplicon, and wherein the secondary measurement's percentile value is 80% or more of the calculated PD-L1 expression value.
30 . (canceled)
31 . The method of claim 21 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the CD8A expression is calculated as high, wherein high CD8A expression equals at least the 67.6 percentile or more of CD8A expression in a population of tumor profiles.
32 . (canceled)
33 . The method of claim 21 , wherein the calculated CD8A expression is confirmed with a secondary measurement of GZMA expression using a second amplicon, and wherein the secondary measurement's percentile value is 80% or more of the calculated CD8A expression value.
34 . The method of claim 21 , wherein the tumor specimen has a tumor content of 40% or more.
35 . The method of claim 21 , wherein the subject is identified as having a checkpoint inhibitor responsive cancer when the PD-L1 expression is calculated as high, the CD8A expression is calculated as high, and the tumor content of the tumor specimen is 40% or more.
36 . (canceled)