Dr Timothy A. Yap - UT MD Anderson Cancer Center, Houston, USA
We presented data at AACR on the KEYLYNK-007 trial which is a tumour-agnostic study of olaparib plus pembrolizumab in homologous recombination repair mutation and homologous recombination deficiency positive advanced cancers. We know that mutations in homologous recombination repair genes, or HRD, rely on PARP enzymes for DNA repair and increased DNA damage promotes immunogenicity through activation of STING and NF-kappa B which leads to a pro-inflammatory signal release and increased immune cell infiltration and it also leads to adaptive upregulation of PD-L1. So in this phase II, tumour-agnostic trial we assessed as combination in molecularly selected patients and by using this tumour-agnostic strategy we were able to actually assess tumour indications outside of the current approved disease settings at the time of trial start.
So in this clinical trial we assessed patients in three different subgroups and all of these patients were actually stratified according to centrally confirmed tumour biomarker status, using the LYNPARZA HRR/HRD assay. In subgroup one we assessed patients with BRCA1 and BRCA2 mutation tumours; in subgroup two we assessed patients with non-BRCA but HRR mutation tumours; in subgroup three we assessed patients with HRD positive tumours without HRR mutations but with a loss of heterozygosity score of at least 16. To the best of our knowledge this is the largest dataset of molecularly selected patients with HRR mutations or HRD positive tumour-agnostic advanced cancers treated with PARP inhibitor plus anti-PD-1 or PD-L1 inhibitor combination therapy.
In this phase II tumour-agnostic trial, the KEYLYNK-007 study, we observed that this combination of olaparib plus pembrolizumab showed promising anti-tumour activity, particularly in BRCA1 and BRCA2 mutation cancers where we observed a median duration of response of 19.1 months. In addition to that we observed early signals of durable anti-tumour efficacy in patients with molecularly selected tumours in indications where olaparib and/or pembrolizumab are not currently approved.
Currently biomarker analysis is ongoing for other biomarkers of response.
