Updated efficacy and safety of entrectinib in children with extracranial solid or primary central nervous system (CNS) tumors harboring <i>ROS1</i> fusions.

10050 Background: Entrectinib is a TRK and ROS1 inhibitor that has shown rapid and durable responses in children with NTRK1/2/3 or ROS1 fusion-positive (fp) extracranial solid or primary CNS tumors in an integrated analysis of the STARTRK-NG (NCT02650401), TAPISTRY (NCT04589845) and STARTRK-2 (NCT02568267) trials. These data led to FDA and EMA approval of entrectinib in pediatric patients &gt; 1 month with NTRK fp tumors. Here we present updated data on pediatric patients with ROS1 fp tumors based on the trials listed above to further describe the efficacy and safety of entrectinib in this population. Methods: Eligible pts were TRK/ROS1 inhibitor-naïve, &lt; 18 years old, with locally advanced/metastatic extracranial solid or primary CNS tumors, with measurable or evaluable-only disease. All pts who received ≥1 daily dose of oral entrectinib are included in the safety-evaluable population. Pts who had a ROS1 fusion and were followed for ≥6 months are included in the ROS1 efficacy-evaluable population. Pts received 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. Primary endpoint: confirmed objective response rate (ORR) per BICR. Key secondary endpoints: ORR in pts 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); safety. Results: At clinical cut-off (16 July 2024), of the 113 safety-evaluable pts, there were 26 pts in the ROS1 efficacy-evaluable cohort. ORR was 69.2% (95% CI 48.2, 85.7). Median TTR was 1.84 months. Median OS was not evaluable. Median duration of survival follow-up was 29.4 months (range 1–80). Efficacy outcomes are shown in the table. The most common related adverse events were weight gain (37.2%), anemia (36.3%), and AST increase (26.5%). Related fracture events occurred in 23% of pts. Conclusions: Entrectinib yielded rapid and durable responses in pediatric pts with ROS1 fp extracranial solid or primary CNS tumors. The safety profile of entrectinib was consistent with previous reports. Clinical trial information: NCT02650401 ; NCT04589845 ; NCT02568267 . Efficacy ROS1 (N=26) Confirmed ORR*, N, % [95% CI] 18, 69.2 [48.2- 85.7] Complete response 4, 15.4 [4.4- 34.9] Partial response 14, 53.8 [33.4- 73.4] Median confirmed DoR*, months (95% CI) NE (16.2- NE) Median TTR*, months (range) 1.84 (1.6- 4.0) CBR*, % (95% CI) 84.6 (65.1- 95.6) Median PFS*, months (95% CI) NE (21.8- NE) Median OS, months (95% CI) NE (NE- NE) *Per BICR; CI, confidence interval; NE, not evaluable.