Clinical outcomes of a prospective multicenter study evaluating a combined circulating tumor DNA (ctDNA) and RNA (ctRNA) liquid biopsy assay in metastatic non-small cell lung cancer (NSCLC).

3062 Background: Genomic profiling of metastatic NSCLC to inform targeted therapy selection is endorsed by numerous guidelines. While tissue biopsy is the mainstay of molecular profiling, liquid biopsy offers a practical real-world approach to non-invasively identify guideline-recommended biomarkers. LIQUIK was a prospective, multicenter, observational cohort study to evaluate the performance of a combined ctDNA and ctRNA liquid biopsy assay, LiquidHALLMARK (LHM ctDNA and ctRNA) in comparison to the ctDNA-only liquid biopsy Guardant360 (G360 ctDNA) and tissue next-generation sequencing (NGS) for biomarker detection in metastatic NSCLC. Diagnostic performance of the primary cohort has been previously presented. Here, we report clinical outcomes after 1-year follow-up of the cohort. Methods: LIQUIK (NCT04703153) enrolled 151 non-squamous NSCLC patients across the USA and Singapore from Apr 2021 to Dec 2022. Enrolled patients were genotyped using tissue NGS, LHM ctDNA and ctRNA, and G360 ctDNA for 9 biomarkers ( EGFR , ALK , RET , ROS1 , BRAF , KRAS , MET , ERBB2 , NTRK1 / 2 / 3 ). Patients were treated according to their physician’s choice of first-line therapy following biomarker testing. Tumor assessments were performed at baseline and within 6 months (mo) of treatment initiation. Overall response rate (ORR), progression-free survival (PFS), and the clinical utility of ctRNA were investigated. Results: Among the 151 patients, 129 were subsequently treated in the first-line setting (49.6% on targeted therapy, 41.1% on chemotherapy, and 30.2% on immunotherapy), with 27 on combination therapy. Of the 64 patients on targeted therapy, 47 had matched biomarker findings from tissue NGS, 47 from LHM ctDNA and ctRNA, and 43 from G360 ctDNA. ORRs of patients on targeted therapy and chemo/immunotherapy were 40.4% and 16.1% respectively. Among patients treated with targeted therapy, ORR was similar between patients with biomarker-matched findings from tissue NGS (45.2%), LHM ctDNA and ctRNA (40.5%), and G360 ctDNA (36.8%). PFS of patients on targeted therapy (median 23.6 mo) was significantly longer than those not on targeted therapy (median 3.8 mo; HR = 0.26; p < 0.001). Median PFS was similar between patients with biomarker-matched findings from tissue NGS (23.6 mo), LHM ctDNA and ctRNA (18.6 mo), and G360 ctRNA (20.1 mo). Overall, incorporation of ctRNA into LHM identified 2 additional biomarker-positive patients. Both ctRNA-exclusive biomarkers were confirmed by tissue NGS, and both patients were treated with biomarker-matched targeted therapy. While one patient was lost to follow-up, the second patient had a partial response to treatment. Conclusions: Treatment outcomes based on liquid and tissue biopsies are comparable. The inclusion of ctRNA in liquid biopsy increases its diagnostic yield of actionable biomarkers. Clinical trial information: NCT04703153 .