Rapid Readouts: Results of the SCOUT and NAVIGATE Trials

David A. Reardon, MD, discusses data from the following presentation:

• Efficacy and Safety of Larotrectinib in Adult and Pediatric Patients With Tropomyosin Receptor Kinase (TRK) Fusion-Positive Primary Central Nervous System (CNS) tumors (Perreault S, ASCO 2021 Annual Meeting, Abstract #2002)
  • The objective of this study is to report results from the phase 2 NAVIGATE basket trial and the phase 1/2 SCOUT trial (NCT02576431 and NCT02637687, respectively) in adult and pediatric patients with TRK fusion–positive central nervous system tumors treated with larotrectinib, a first-generation TRK inhibitor.
  • Study Design
    • NAVIGATE: age 12 years or older; advanced solid tumors, TRK-positive cancer (N=9)
    • SCOUT: age less than21 years; locally advanced or metastatic solid tumors or CNS tumors (N=24)
    • Primary end point: objective response rate (ORR) by RANO or RECIST v1.1 criteria if target lesions inadequate for RANO (n=5)
  • Efficacy
    • The evaluable patients (N=33) showed an ORR of 20% and a disease control rate (DCR) of 73% at greater than or equal to24 weeks; responses were durable, with a median progression-free survival (PFS) of 18.3 months and median overall survival (OS) not reached during the trial but 12-month OS rate was 85%.
    • Responses were seen across patient populations (adult and pediatric) and across disease grade (low and high).
    • At data cutoff, 18 patients were still receiving treatment.
  • Safety
    • There were limited grade 3 treatment-related adverse events (AEs), mostly neutropenia, and no grade 4 or 5 treatment-related AEs.
    • There was a small number of grade 1 or 2 neurologic AEs, but most were thought to not be treatment related.
  • Conclusions
    • The data showed objective response and durable stable disease in patients with primary CNS tumors treated with larotrectinib, with no treatment-related safety concerns.
    • The results support testing for NTRK gene fusions and consideration of TRK-targeting agents in patients with primary CNS tumors of all ages.