FDA Approves Larotrectinib for NTRK-Positive Solid Tumors

FDA

The FDA has granted full approval to larotrectinib (Vitrakvi) for the treatment of adult and pediatric patients with solid tumors harboring 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.1

The regulatory decision was supported by data from three single-arm studies: the phase 1 LOXO-TRK-14001 (NCT02122913), phase 1/2 SCOUT (NCT02637687), and phase 2 NAVIGATE (NCT02576431) trials.

Pooled data from the 3 studies showed that evaluable patients achieved an overall response rate (ORR) of 60% (95% CI, 55%-65%), comprising a complete response (CR) rate of 24% and a partial response (PR) rate of 36%. Pathological CRs were reported in 5% of patients. The median duration of response (DOR) was 43.3 months (95% CI, 32.5-not evaluable [NE]).

In November 2018, larotrectinib received accelerated approval from the FDA in the same indication for adult and pediatric patients with solid tumors harboring NTRK gene fusions.2

“This first full approval of an NTRK inhibitor by the FDA represents the culmination of research and dedication by the Bayer team,” Chandra Goda, executive director, U.S. Vitrakvi brand lead at Bayer, stated in a news release. “We are proud to deliver on our promise for patients with this significant step forward, providing a treatment option for pediatric and adult patients living with NTRK gene fusion–positive cancers. This milestone reinforces Bayer's commitment to delivering innovative solutions that address the unique needs of patients and their families."

Safety data showed that the most common adverse effects (AES) reported in at least 20% of patients included increased aspartate aminotransferase levels, increased alanine aminotransferase levels, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase levels, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash.

Serious AEs consisted of central nervous system (CNS) toxicity, bone fractures, and liver toxicity.

"The full approval of [larotrectinib] by the FDA is a welcome step forward, solidifying its place as a treatment option for patients with NTRK gene fusion–positive cancers," Andrea Ferris, president and chief executive officer of the LUNGevity Foundation, added in a news release.1 "This milestone not only benefits patients today but also paves the way for further advancements in NTRK gene therapies in the future."

Further Data From LOXO-TRK-14001, SCOUT, and NAVIGATE

Long-term efficacy and safety data from the 3 studies presented at the 2023 ASCO Annual Meeting showed that efficacy-evaluable patients with NTRK gene fusion–positive solid tumors (n = 180) achieved an ORR of 57% (95% CI, 50%-65%).3 At a median follow-up of 32.3 months, the median DOR was 43.3 months (95% CI, 29.2-not evaluable [NE]). The 24- and 48-month DOR rates were 66% and 48%, respectively.

At a median follow-up of 28.5 months, patients achieved a median progression-free survival (PFS) of 24.6 months (95% CI, 11.3-35.5). The respective 24- and 48-month PFS rates were 51% and 39%.

The median overall survival (OS) was 48.7 months (95% CI, 38.5-NE) at a median follow-up of 33.8 months. The 24- and 48-month OS rates were 69% and 51%, respectively.

The pooled analysis included patients at least 18 years of age with non–primary CNS NTRK fusion–positive solid tumors who were treated across the three single-arm clinical trials. The majority received larotrectinib at a dose of 100 mg twice per day.

The most common tumor types included in the analysis were lung (15%), soft tissue sarcoma (15%), thyroid (14%), salivary gland (13%), and colon (12%).

References

1. U.S. FDA grants full approval of Vitrakvi (larotrectinib) for adult and pediatric patients with NTRK gene fusion-positive solid tumors. News release. Bayer. April 10, 2025. Accessed April 10, 2025. https://www.businesswire.com/news/home/20250409395229/en/U.S.-FDA-Grants-Full-Approval-of-VITRAKVI-larotrectinib-for-Adult-and-Pediatric-Patients-with-NTRK-Gene-Fusion-Positive-Solid-Tumors
2. FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA. November 26, 2018. Accessed April 10, 2025. https://www.fda.gov/drugs/fda-approves-larotrectinib-solid-tumors-ntrk-gene-fusions
3. Hong DS, Drilon A, Tan DSW, et al. Larotrectinib long-term efficacy and safety in adult patients (pts) with tropomyosin receptor kinase (TRK) fusion cancer. J Clin Oncol. 2023;41(suppl 16):3141. doi:10.1200/JCO.2023.41.16_suppl.3141