FDA-Approved and Investigational TRK Inhibitors

Alexander Drilon, MD, a medical oncologist, and chief of the Early Drug Development Service at Memorial Sloan Kettering Cancer Center, discusses targeted therapies for the patients with NTRK gene fusion-positive cancers.

In 2018, the FDA granted approval to larotrectinib (Vitrakvi) for use in adult and pediatric patients with solid tumors that have an 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.

The approval of Larotrectinib was followed a year later with the approval of another TRK inhibitor, entrectinib (Rozlytrek), which is indicated for the treatment of adult and adolescent patients with solid tumors harboring an NTRK gene fusion and who have no alternative effective therapies available.

Aside from FDA-approved agents, studies are ongoing to investigate the efficacy and safety of novel TRK inhibitors like selitrectinib (formerly LOXO 195), repotrectinib (TPX-0005), and taletrectinib (DS-6051b/AB-106).

Transcription:

0:08 | There are 2 approved TRK inhibitors for the treatment of any cancer with an NTRK fusion, and one of them is called larotrectinib. It is a selective inhibitor of TRK A, B and C. The second one is called entrectinib, and that is a good inhibitor of TRK A, B and C but it's a multi kinase inhibitor that also hits for ROS1 and has to a lesser degree activity against ALK.

0:36 | Both of these drugs are approved in a tumor agnostic fashion and beige agnostic fashion for patients whose cancers harbor these fusions. Approval has been granted in many different regulatory environments around the world.

0:52 | Now, there are next-generation TRK inhibitors that are currently in clinical trials. Examples are selitrectinib, repotrectinib, and taletrectinib. These drugs are designed to target resistance mutations that might emerge with the first-generation agents.