We just presented, actually, on Saturday morning results from the biomarker part from the JAVELIN Renal 101 study. This was a large study, over 800 patients that were randomised to receive standard sunitinib or the PD-L1 inhibitor avelumab plus axitinib, it’s another VEGF TKI similar to sunitinib. We reported on the study and published it in The New England Journal of Medicine showing a progression free survival and a response rate advantage over single agent, from the combination over single agent sunitinib.

So here we reported on baseline tissue-based biomarker collected within a year and we looked at PD-L1 and CD8 at the invasion margin in terms of immunohistochemistry. Compared to what’s been reported in the literature, our hypothesis did hold through. PD-L1 was a negative prognostic indicator in patients that received single agent sunitinib. PD-L1 status didn’t impact the benefit from avelumab and axitinib. On the other hand, CD8 was the opposite – high CD8 counts at the invasion margin were associated with a higher progression free survival in patients on the combination arm and the opposite on sunitinib, in patients that received sunitinib.

Then we went and worked with RNA-Seq data to look at gene expression and came up with a gene expression signature. We started by over 4,000 genes down to 26 genes involved in immune related properties, both at the T-cell level and K level macrophage. That signature was able to differentiate, if you have high versus low signature, progression free survival in patients that received a combination but wasn’t of any value, any prognostic or predictive value, in patients that received sunitinib. We validated our results from an earlier study with that signature called the JAVELIN Renal 101 signature.
We finally looked at the mutational landscape. We had over 700 patients who had whole exome sequencing data and we came up with very interesting findings. I’m not going to go into details, I invite you to look at the presentation. But, for example, PTEN, the tumour suppressor gene PTEN, was an adverse prognostic factor for benefit from the combination.

We also looked at certain SNPs that may predict different binding at the level of the Fc gamma receptor because avelumab, the PD-L1 inhibitor here, is a wildtype IgG1 and actually there was no difference. I’m proud of this dataset because it blends clinical science and translational research together, it has a control arm, it’s 700 patients, it’s an academia industry partnership and hopefully it will give us insight towards the next step, how to treat advanced RCC and the biomarker field in general.