Larotrectinib (TRK inhibitor) delivers 65% ORR and 42-mo DoR in non-primary CNS NTRK fusion cancers

Larotrectinib (laro) is a first-in-class, highly selective TRKA/B/C (NTRK1/2/3) inhibitor evaluated in an updated pooled analysis of 3 trials (SCOUT/NAVIGATE/LOXO-TRK-14001; data cutoff July 20, 2025) in adult and pediatric patients with non-primary CNS NTRK fusion cancers (n=304; 28 tumor types; 25 with baseline CNS metastases). Independent review showed ORR 65% (95% CI 59–70) with 20% CR plus 6% pathologic CR; median DoR 42 months, median PFS 26 months, and median OS not reached (5-year OS 61%) at median follow-up ~54–65 months; median time to response was 1.8 months. Safety was largely low-grade (Grade 1/2 TRAEs 62%); Grade 3/4 TRAEs occurred in 24% and 2% discontinued for TRAEs—an overall tolerability profile that looks favorable versus multi-agent chemotherapy typically used across these heterogeneous histologies, and efficacy that benchmarks well against the other approved TRK inhibitor entrectinib (pooled ORR ~57–61% and mPFS ~14 months in NTRK fusion solid tumors).