Bespoke circulating tumor DNA (ctDNA) analysis as a predictive biomarker in solid tumor patients (pts) treated with single agent pembrolizumab (P)

Abstract

Background: Limited data exist in the clonal dynamics of serial ctDNA as a predictive biomarker in advanced solid tumor pts receiving immune checkpoint blockade. Methods: Pts with mixed solid tumors received single agent P (anti-PD-1) 200 mg IV Q3wks in the investigator-initiated phase II INSPIRE trial (NCT02644369). ctDNA was assayed at baseline (B) and start of cycle 3 (C3) using a pt-specific amplicon-based NGS assay (Signatera™). Samples were considered ctDNA positive if≥2 of 16 pt-specific targets met the qualifying confidence score threshold. Results: Of 94 pts are presented. Demographics: male 38%; median age=55 yrs (range 21-81); triple negative breast (19%), ovarian (19%) and head and neck (17%) cancers comprised the major malignancies. Median no. of P cycles=3 (range 1-35); follow up was 14m (range 0.6-35.4); RECIST responses: CR 3.2% (n=3), PR 14% (n=13), CBR (CR+PR+SD>6 cycles) 28% (n=26), RECIST/clinical PD (n=61/18; 65%/19%). Median PFS=2.5m and median OS=14m. In all 94 pts, ctDNAB correlated with PFS (adjusted HR 0.53, 95% CI 0.34-0.84, p=0.01) and OS (adjusted HR 0.47, 95% CI 0.28-0.8, p=0.01). Among 74 pts with both ctDNAB and ctDNAC3, the change (ΔctDNA) correlated with clinical efficacy parameters (Table). Conclusions: Strong correlations exist between both ctDNAB and ΔctDNA with clinical outcome, suggesting both prognostic and predictive values in pts with mixed solid tumors.