At the moment we are using widely PD-1 and PD-L1 agents. It does seem in the advanced setting that we do need a marker of pre-existing immunity. At the moment these agents have been approved with a PD-L1 assay. Unfortunately, there’s a different PD-L1 assay which are different with each different drug from a different company, so this has caused a lot of confusion especially because they’re not the same...
At the moment we are using widely PD-1 and PD-L1 agents. It does seem in the advanced setting that we do need a marker of pre-existing immunity. At the moment these agents have been approved with a PD-L1 assay. Unfortunately, there’s a different PD-L1 assay which are different with each different drug from a different company, so this has caused a lot of confusion especially because they’re not the same. So, we don’t really know what to do with discordant results and how many PD-L1 assays we should be testing and the reproducibility of these assays as well is not being tested. So we don’t really know what’s biologically correct or therapeutically correct for these assays because they’re different. And it’s a lot of mess at the moment from that point of view.
We’ve been looking at TIL which is simply quantity of immune infiltration. This also seems to predict very well that the patient does have pre-existing immunity and also benefits from these agents. So, we think from a pragmatic point of view, it would be good to do both markers because you have quantity which we know is important, and then you have a marker of PD-L1 which is the target for these drugs. But they’re strongly correlated so it’s very hard not to have high TIL and not to be PD-L1-positive. So it also provides some sort of feedback to the clinicians that they’re perhaps on the right track. So if you have high TIL but PD-L1-negative, maybe we should be doing another PD-L1 assay as well for that patient, because you don’t want them to miss out because these agents have been shown to be associated with improved overall survival. And so patients with advanced disease, that’s really important.