Résumé
Abstract only 3017 Background: Entrectinib potently inhibits kinases encoded by the NTRK and ROS1 genes. It achieves therapeutic levels in the CNS with antitumor activity in intracranial tumor models. We report integrated data (31 May 2018 cut-off) from 3 Phase 1/2 entrectinib trials (ALKA-372-001, EudraCT 2012-000148-88; STARTRK-1, NCT02097810; STARTRK-2, NCT02568267) for a large cohort of adults with ROS1 fusion-positive NSCLC ( ROS1+) or NTRK fusion-positive solid tumors ( NTRK+), with/without baseline CNS metastases. Methods: Pts had locally advanced/metastatic NTRK+ or ROS1+ tumors by nucleic acid-based confirmation. Baseline CNS metastases were identified by CT/MRI. Tumor assessments were at wk 4, then every 8 wk by blinded independent central review (RECIST v1.1). Primary endpoints: ORR, DOR. Secondary endpoints: CBR, PFS, OS, intracranial efficacy and safety. Results: Most pts had ≥1 prior therapy; 33% had baseline CNS metastases. Outcomes for the ROS1+ NSCLC (n = 53) and NTRK+ solid tumors (n = 54; 24% sarcoma, 18% NSCLC) efficacy evaluable data sets are shown (table). Entrectinib was tolerable with a manageable safety profile; most treatment-related AEs were grade 1–2. Conclusions: Entrectinib induced clinically meaningful durable responses in pts with ROS1+ NSCLC or NTRK+ solid tumors with or without CNS disease. Clinical trial information: NCT02097810; NCT02568267. [Table: see text]