At ASCO this year we presented results from the ASCENT-04 study, specifically looking at a biomarker analysis within this trial. The ASCENT-04 trial was a randomised phase III study that had looked at the combination of sacituzumab govitecan with pembrolizumab and compared it to chemotherapy plus pembrolizumab amongst patients who have PD-L1+ metastatic triple-negative breast cancer that has been previously untreated. We had seen the results from this phase III study last year where we saw that the combination of sacituzumab and pembrolizumab led to a significant improvement in progression free survival compared to chemotherapy plus pembrolizumab and this was very clinically meaningful.

So while this now clinical data has suggested benefit, the question has been are there potential biomarkers that could help you select out which patients are deriving the greatest benefit from therapy and maybe if there are patients who wouldn’t derive greater benefit from sacituzumab plus pembrolizumab. So we specifically looked at archival tumour tissue from this trial; about half of the tissue that was looked at came from a metastatic site. We looked at specific biomarkers, including TROP-2 which was assessed by immunohistochemistry using an H-score. We also looked at BRCA mutation status, which was determined by whole exome sequencing off of tumour tissue since we didn’t have sufficient numbers of patients that had germline testing done locally. So, in essence, we were assessing tumour BRCA mutation status. We also looked at HER2 expression which was centrally tested by immunohistochemistry with reflex ISH testing.

What we found was that patients did better with sacituzumab plus pembrolizumab compared to chemo plus pembrolizumab, irrespective of TROP-2 expression levels. So we had categorised patients into quartiles by TROP-2 H-scores and found that patients with low quartiles compared to high quartiles, all of them really always did better with SG plus pembro compared to chemo plus pembro. We also found that patients with BRCA mutant as well as BRCA wild-type tumours derived a benefit from SG plus pembro compared to chemo plus pembro, again irrespective of BRCA mutation status. Similarly, benefit was seen for SG plus pembro compared to chemo plus pembro irrespective of HER2 expression status – whether the tumour was HER2 IHC zero or HER2 low, SG plus pembro always did better than chemo plus pembro.

So in essence these findings really just confirm the benefits that we know with SG plus pembro and was not able to identify a biomarker predictor of benefit because everyone that was looked at really did better with SG plus pembro compared to chemo plus pembro, irrespective of the biomarker status. There is other work ongoing to further define if there may be particular subsets of patients who derive greater benefit than others. So we’ll have more data from the whole exome sequencing that was done in this trial, there will be other modalities to look at TROP-2 expression, including using a digital analysis. We’ll have data in the future looking at tumour infiltrating lymphocytes. So I think we’ll see a lot more biomarker data to come from this trial which will be really exciting.