Efficacy/safety of entrectinib in patients (pts) with ROS1-positive (ROS1+) advanced/metastatic NSCLC from the Blood First Assay Screening Trial (BFAST).
Authors: Peters Solange , Gadgeel Shirish M. , Mok Tony S. K. , Nadal Ernest , Kilickap Saadettin , Perol Maurice , Cadranel Jacques , Sugawara Shunichi , Chiu Chao-Hua , Moskovitz Mor , Yu Chong-Jen , Tanaka Tomohiro , Nersesian Rhea , Shagan Sarah M. , Maclennan Margaret , Mathisen Michael , Bhagawati Prasad Vijay N S , Archer Venice Rosalie , Dziadziuszko Rafal 
Published: June 2022

LBA9023 Background: Tissue-based biomarker testing remains challenging as tumor biopsies are often inadequate for comprehensive biomarker testing and repeat biopsies can be risky in pts with advanced/metastatic NSCLC. These challenges could be overcome by using blood-based testing to identify the most appropriate targeted therapy. BFAST (NCT03178552) is a global open-label, multicohort trial evaluating the efficacy and safety of selected therapies in pts with advanced/metastatic NSCLC harboring actionable genetic alterations, as identified by next-generation sequencing (NGS) in cell-free DNA (liquid biopsies). We present data from the ROS1+ cohort: this is the first evaluation of entrectinib efficacy in pts identified by prospective blood-based NGS. Methods: In this single-arm analysis, adults (≥18 years) with treatment-naïve measurable stage IIIB/IV NSCLC, identified as ROS1+ by the FoundationOne®Liquid CDx CTA blood-based NGS test, received oral entrectinib 600 mg/day until disease progression (PD), unacceptable toxicity, consent withdrawal or death. Pts with asymptomatic brain metastases at screening were eligible. Tumor scans were performed at baseline and every 8 weeks thereafter for all disease involvement areas (brain imaging not mandated in pts without baseline CNS disease). Primary endpoint: investigator (INV)-assessed objective response rate (ORR; RECIST 1.1). Secondary endpoints: INV-assessed duration of response (DoR) and progression-free survival (PFS); independent review facility (IRF)-assessed ORR, DoR, PFS; overall survival (OS); time to CNS PD; safety. Results: 55 pts with ROS1+ NSCLC identified by blood-based NGS were enrolled and treated with entrectinib. Median age was 56 yrs; 58% of pts were female and 75% had no history of tobacco use. Non-squamous adenocarcinoma was the most common histology (n = 48/55; 87%); 4 pts (7.3%) had baseline CNS disease. Median follow-up: 18.3 months. At data cut-off (26 Nov 2021, n = 54 pts with measurable disease), confirmed ORR was 81.5% (n = 44/54; 95% CI 68.6–90.8) by INV (2 complete responses [CR], 42 partial responses [PR]) and IRF (3 CR, 41 PR). Median DoR was 13.0 months (95% CI 6.3–18.4) by INV and 16.7 months (95% CI 5.6–24.0) by IRF. Median PFS was 12.9 months (95% CI 8.7–18.5) by INV, and 14.8 months (95% CI 7.2–24.0) by IRF. OS data were immature with 20 events (36.4%) recorded. Median time to CNS PD was not reached (INV: 9 events; IRF: 6 events). Most treatment-related adverse events were non-serious with no treatment-related deaths. Conclusion: These data support the clinical value of blood-based NGS as another method to inform clinical decision-making in ROS1+ NSCLC. Pts with ROS1+ NSCLC (by blood-based NGS) treated with entrectinib showed deep and durable responses, consistent with results from entrectinib trials that used tissue-based testing. No new safety signals were observed. Clinical trial information: NCT03178552.