Looking at the pipeline for larotrectinib, it shows an accelerated course, which can be attributed to the drug`s potential to fulfill an unmet need in oncology.

Following larotrectinib`s discovery in 2013, in in vitro models, the agent demonstrated high potency against TRKA, TRKB, and TRKC, which are 3 TRK proteins that are encoded by NTRK1, NTRK2, and NTRK3.

In solid tumors, the agent was preclinically tested on a lung adenocarcinoma cell line harboring an MPRIP–NTRK1 fusion, as well as a colorectal cancer cell line harboring a TPM3-NTRK1 fusion.Larotrectinib also had preclinical evaluation in hematologic malignancies in an acute myeloid leukemia cell line harboring an ETV6-NTRK3 fusion. Administration of larotrectinib in these cell lines led to a significant reduction in tumor growth. Responses to larotrectinib in these preclinical models occurred within 2 weeks of treatment initiation.1

Larotrectinib works by blocking the adenosine triphosphate binding site. The drug appears to have high binding affinity for all 3 TRK receptors.