Encorafenib + binimetinib (BRAF/MEK inhibition) validates FoundationOne Liquid/Tissue CDx for BRAF V600E NSCLC selection

FoundationOne®Liquid CDx (F1LCDx; plasma ctDNA) and FoundationOne®CDx (F1CDx; tissue) are FDA-approved companion diagnostics for identifying BRAF V600E–mutant metastatic NSCLC patients eligible for encorafenib (selective BRAF inhibitor) plus binimetinib (MEK1/2 inhibitor), and this PHAROS (Phase 2; NCT03915951) “bridging” analysis tested concordance vs clinical trial assays (CTAs). In ctDNA-sufficient samples (tumor fraction ≥1%), F1LCDx achieved 83.3% positive percent agreement (PPA; 95% CI 68.1%-92.1%) while tissue F1CDx achieved 93.2% PPA (85.0%-97.0%), supporting tissue as the more reliable “catch-all” with liquid as a complementary option when tissue is limited. Clinically, ORR by independent review was similar when patients were selected by these CDx tests vs CTA: F1LCDx+/CTA+ ORR 60.4% vs 63.3% in CTA+; F1CDx+/CTA+ ORR 70.6% vs 64.1% in CTA+—well above typical single-agent docetaxel response rates in unselected post-platinum NSCLC (~7%-10%), though cross-trial comparisons are imperfect.