Dr Hong on the FDA Approval of Larotrectinib for NTRK+ Solid Tumors

"This full approval confirms what we knew [at the time of the accelerated approval]: patients with NTRK fusions clearly benefit from treatment with larotrectinib, regardless of tumor type."

David S. Hong, MD, deputy chair of the Department of Investigational Cancer Therapeutics in the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, discussed the clinical significance of the FDA’s full approval of larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with solid tumors harboring an NTRK gene fusion.

On April 10, 2025, the FDA granted full approval to larotrectinib for the treatment of patients with NTRK gene fusion–positive solid tumors without a known acquired resistance mutation; that 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 action built upon the drug’s initial accelerated approval in 2018; the full approval was supported by expanded efficacy and safety data from three single-arm clinical trials: the phase 1 LOXO-TRK-14001 (NCT02122913), the phase 1/2 SCOUT (NCT02637687), and the phase 2 NAVIGATE (NCT02576431) studies.

Pooled efficacy data from these trials demonstrated that among evaluable patients, larotrectinib produced an overall response rate of 60% (95% CI, 55%-65%), which included a complete response (CR) rate of 24% and a partial response (PR) rate of 36%. Additionally, 5% of patients achieved a pathological CR. The median duration of response was 43.3 months (95% CI, 32.5-not evaluable).

Hong emphasized that the full approval reinforces the durable efficacy previously observed and confirms the tumor-agnostic utility of larotrectinib in this molecularly defined population. He noted that benefit has been consistently observed across pediatric and adult populations, regardless of tumor histology.

In terms of safety, Hong described larotrectinib as one of the most well-tolerated targeted therapies evaluated in his drug development experience. Common adverse effects include dizziness and transient elevations in liver function tests (LFTs), both of which are typically manageable with dose adjustments or temporary treatment interruption. Serious toxicities are rare, and no new safety signals emerged in the expanded data set, Hong concluded.