Agent Description
Larotrectinib is a potent, oral and highly selective tropomyosin receptor kinase (TRK) inhibitor approved by the U.S. FDA for the treatment of adult and pediatric patients with solid tumors that:
- have a neurotrophic receptor tyrosine kinase (NTRK) gene fusion without a known acquired resistance mutation,
- are metastatic or where surgical resection is likely to result in severe morbidity, and
- have no satisfactory alternative treatments or that have progressed following treatment.
This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.
Mechanism of Action
ATP-competitive kinase inhibitor of TrkA/B/C
Classification
Small molecule, tyrosine kinase inhibitor
Molecular Target
NTRK-1, NTRK-2, NTRK-3 gene fusions; TrkA/B/C fusion proteins
Monograph
Larotrectinib is approved in the U.S. in both adult and pediatric patients based on on-going phase 1 and phase 2 trials. Larotrectinib is also being studied in the ECOG-ACRIN NCI Adult MATCH and the COG-NCI Pediatric MATCH phase 2 trials. Larotrectinib has low nanomolar potency against TrkA (NTRK1), TrkB (NTRK2), and TrkC (NTRK3) with no other kinase inhibition at physiologically achievable doses. Larotrectinib is available in both capsule and liquid formulations.
Studies of Interest
N/A
Information collaborator would like included in investigator proposals
N/A