Clinical Validation of Tissue and Liquid Companion Diagnostics for BRAF V600E Detection in Non-Small Cell Lung Cancers from the PHAROS Study.

UNLABELLED: The detection of biomarkers in blood or tumor tissue samples may affect the efficacy of targeted therapy in patients with non-small cell lung cancer (NSCLC). The FoundationOne Liquid CDx (F1LCDx) and tissue FoundationOne CDx (F1CDx) companion diagnostic tests were approved by the US Food and Drug Administration to identify patients with BRAF V600E-mutant metastatic NSCLC who may benefit from encorafenib combined with binimetinib. This clinical bridging study aimed to establish F1LCDx and F1CDx as companion diagnostics for the identification of patients with BRAF V600E-mutant metastatic NSCLC and to determine concordance between these tests and clinical trial assays (CTA) in samples from patients enrolled in the phase II PHAROS trial. In samples with sufficient circulating tumor DNA (ctDNA; defined as tumor fraction ≥1%), F1LCDx testing revealed a positive percent agreement (PPA) of 83.3% (Wilson score two-sided 95% confidence interval, 68.1%-92.1%). F1CDx testing revealed a PPA of 93.2% (85%-97%), suggesting that F1CDx may robustly identify patients with BRAF V600E-mutant NSCLC and complement F1LCDx testing in this population. The efficacy of encorafenib plus binimetinib in patients selected by F1LCDx or F1CDx was based on the objective response rate (ORR) by independent radiology review in the PHAROS trial. The estimated ORRs in the F1LCDx+/CTA+ population were 60.4% versus 63.3% in the CTA+ population. Similarly, the estimated ORRs in the F1CDx+/CTA+ population were 70.6% versus 64.1% in the CTA+ population. These findings suggest that both tests may be clinically useful in predicting the efficacy of encorafenib plus binimetinib in patients with metastatic NSCLC.

SIGNIFICANCE: This clinical bridging study assessed F1LCDx and tissue F1CDx companion diagnostic tests for identifying patients with BRAF V600E-mutant metastatic NSCLC. Results support both tests in identifying patients and predicting an objective response in patients who may be eligible for treatment with encorafenib combined with binimetinib.