Entrectinib in ROS1-positive advanced non-small cell lung cancer: the phase 2/3 BFAST trial

Although comprehensive biomarker testing is recommended for all patients with advanced/metastatic NSCLC before first-line therapy, tissue availability can limit testing. Liquid biopsy genomic testing can overcome limitations of tissue sampling to identify biomarker-informed treatments. The global, open-label, multicohort Blood First Assay Screening Trial (BFAST) evaluates therapies in advanced/metastatic NSCLC with targetable alterations identified by liquid biopsy. We report Cohort D (ROS1-positive). Adults with stage IIIB/IV ROS1-positive NSCLC detected by liquid biopsy received entrectinib 600 mg daily. At data cutoff (November 2021), 55 patients were enrolled (54 with measurable disease). The cohort met its primary endpoint: confirmed objective response rate (ORR) by investigator was 81.5%, consistent with the integrated tissue-selected entrectinib analysis (investigator-assessed ORR 73.4%; May 2019 cutoff). Safety was consistent with prior reports. Findings support the clinical value of liquid biopsies to inform decision-making, offering a less invasive and faster diagnostic approach than tissue testing that may expedite clinical decisions in advanced/metastatic NSCLC. ClinicalTrials.gov: NCT03178552.

Solange Peters, Shirish M. Gadgeel, Tony Mok, Ernest Nadal, Saadettin Kilickap, Aurélie Swalduz, Jacques Cadranel, Shunichi Sugawara, Chao-Hua Chiu, Chong-Jen Yu, Mor Moskovitz, Tomohiro Tanaka, Rhea Nersesian, Sarah M. Shagan, Margaret Maclennan, Michael Mathisen, Vijay Bhagawati-Prasad, Cheick Diarra, Zoe June Assaf, Venice Archer, Rafal Dziadziuszko