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NSCLC: Tumor mutational burden associated with efficacy

Atezolizumab (atezo,anti-PD-L1) is FDA approved for 2L+ NSCLC based on results from the randomised OAK- and POPLAR-trials with atezo showing superior efficacy vs. docetaxel. It has been shown that the tumor mutational burden in blood (bTMB) in tissue correlates with atezo efficacy in 1L+ NSCLC. To address the significant challenge of consistently obtaining sufficient tumour tissue for molecular testing, a novel blood-based assay to measure bTMB has been developed. This approach was used to analyse plasma samples from OAK and POPLAR to correlate bTMB with atezo clinical activity.

The biomarker evaluable population (BEP) included 794 patients (pts), with blood samples available for targeted genomic sequencing. The bTMB assay interrogates single nucleotide variants (SNVs) in 394 genes from cell-free DNA in plasma and reports a score based on the number of high-confidence SNVs identified. The BEP was grouped by bTMB cut points based on the minimum number of SNVs present.

In POPLAR, improved PFS and OS HRs with atezo vs doc were observed at a range of bTMB cut points compared with the ITT and BEP. In AOK, PFS benefit was observed at bTMB cut points over 10 compared with BEP (importantly bTMB did not correlate with PD-L1)
These analyses represent the first demonstration of a new assay measuring bTMB that may predict atezo clinical efficacy in 2L+ NSCLC, providing a non invasive biomarker to identify pts who may derive clinical benefit from single agent checkpoint inhibition.

Gandara D et al., abstract 1295O: Blood based biomarkers for cancer immunotherapy: Tumor mutational burden in blood (bTMB) is associated with improved atezolizumab (atezo) efficacy in 2L+NSCLC (POPLAR and OAK)