Efficacy and safety of entrectinib in children with extracranial solid or primary central nervous system (CNS) tumors harboring NTRK or ROS1 fusions.

10000 Background: Entrectinib previously yielded durable responses in children with NTRK or ROS1 fusion-positive extracranial solid or primary CNS tumors in STARTRK-NG (NCT02650401). We present updated data from STARTRK-NG, TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267): pediatric patients from these trials were combined to enable an integrated efficacy and safety analysis on a larger cohort than previously. Methods: Eligible patients were TRK or ROS1 inhibitor naïve and aged < 18 years, had locally advanced or metastatic extracranial solid or primary CNS tumors harboring an NTRK or ROS1 fusion, and had measurable or evaluable-only disease. Once enrolled, patients received ≥1 daily dose of oral entrectinib until disease progression, unacceptable toxicity, or consent withdrawal. Tumor responses were confirmed by blinded independent central review (BICR) per RECIST v1.1 or RANO criteria. Patients were included if they had been followed for ≥6 months. The primary endpoint was confirmed objective response rate (ORR) per BICR. Key secondary endpoints included ORR in patients with baseline measurable disease per BICR, duration of confirmed response (DoR), time to confirmed response (TTR), clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Results: At clinical cutoff (16 July 2023), out of 91 safety-evaluable patients (regardless of fusion), 44 patients in the NTRK cohort and 20 patients in the ROS1 cohort were efficacy evaluable. Median duration of survival follow-up was 24.2 months ( NTRK: range 1–66) and 27.6 months ( ROS1: range 1–73). The ORR was 72.7% (95% CI 57.2–85.0) in the NTRK cohort and 65.0% (95% CI 40.8–84.6) in the ROS1 cohort. In patients with baseline measurable disease, the ORR was 81.1% ( NTRK: n=30/37; 95% CI 64.8–92.0) and 62.5% ( ROS1: n=10/16; 95% CI 35.4–84.8). Efficacy outcomes are shown in the Table. The most common adverse events were pyrexia (50.5%), vomiting (40.7%) and anemia (40.7%). Conclusions: Entrectinib continued to yield rapid and durable responses in pediatric patients with extracranial solid or primary CNS tumors harboring an NTRK or ROS1 fusion. The safety profile of entrectinib was in line with previous reports. Clinical trial information: NCT02650401 / NCT04589845 / NCT02568267 . [Table: see text]