Examining Larotrectinib in NTRK Fusion+ Lung Tumors

David S. Hong, MD, deputy chair, Department of Investigational Cancer Therapeutics, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, discusses larotrectinib (Vitrakvi) and its mechanism of action.

Currently, there are 2 NTRK inhibitors which exist and are approved by the FDA for patients with NTRK fusion-positive disease. These include larotrectinib and entrectinib (Rozlytrek).

At the 2022 World Conference on Lung Cancer, 2 trials were presented which further demonstrated the favorable efficacy and survival outcomes with larotrectinib in patients with lung cancer and NTRK fusions.

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0:08 | Larotrectinib was the first approved NTRK inhibitor and it was approved for all patients who have NTRK fusions regardless of age, regardless of tumor type, regardless of NTRK fusion partner. There are 3 NTRK genes, NTRK1, NTRK2, NTRK3, and there are multiple different partners. It was an accelerated approval for a breakthrough indication that led to the first small molecule inhibitor that was a tumor agnostic approval. I do think at this point that it is the most potent NTRK inhibitor out there.

1:01 | We did a recent analysis and with Alexander Drilon, MD, we looked at the long term efficacy and safety of larotrectinib in this pooled analysis of NTRK fusion patients. This was from 3 trials that ultimately led to the approval. There was the adult phase 1, which I led, and there was the pediatric phase 1 and 2 called the SCOUT trial [NCT02637687], and then there was the NAVIGATE study [NCT02576431], which was helped led by Dr. Drilon. Those trials, particularly the phase 2, are still enrolling patients.