FDA Awards Full Approval to Larotrectinib in NTRK+ Solid Tumors

• The FDA has granted full approval to larotrectinib (Vitrakvi) for patients with solid tumors harboring an NTRK gene fusion without a known acquired resistance mutation.
• This indication is for solid tumors that are either metastatic or located where surgical removal would likely cause significant health problems and have no adequate alternative treatment options or have continued to grow despite previous treatment.
• Data from studies support this approval: LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

Larotrectinib has received full FDA approval for adult and pediatric patients with solid tumors that have an NTRK gene fusion without known acquired resistance, are metastatic or where surgical resection is likely to result in severe morbidity, and lack satisfactory alternative treatments or have progressed after prior therapy.¹

This approval is supported by data from 3 multicenter, open-label, single-arm trials: the phase 1 LOXO-TRK-14001, phase 1/2 SCOUT, and phase 2 NAVIGATE trials.

In an analysis of all 3 studies that included pediatric and adult patients with unresectable or metastatic solid tumors harboring an NTRK gene fusion (n = 339), pooled efficacy results demonstrated an overall response rate (ORR) of 60% (95% CI, 55%-65%) with a complete response (CR) rate of 24% and a partial response (PR) rate of 36%. A total of 5% of patients with CRs were pathological complete responses (pCR), defined as patients with no viable tumor cells and negative margins after surgical resection and no other disease sites. The median duration of response (DOR) for these patients was 43.3 months (95% CI, 32.5 months to not evaluable).

“This first full approval of an NTRK inhibitor by the FDA represents the culmination of research and dedication by the Bayer team,” said Chandra Goda, executive director, US Vitrakvi brand lead at Bayer, 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."

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

In the pooled analysis of all 3 studies, patients were required to have progressed following systemic therapy for their disease, if available, or would have required surgery with significant morbidity for locally advanced disease.¹

The primary end points were ORR and DOR, as determined by a blinded independent review committee according to RECIST v1.1. Additionally, experts evaluated safety in 444 patients across the 3 trials.

For safety, the most common adverse events (AEs) seen in 20% of patients or more were increased aspartate transferase, increased alanine transaminase, anemia, hypoalbuminemia, musculoskeletal pain, increased alkaline phosphatase, leukopenia, lymphopenia, neutropenia, hypocalcemia, fatigue, vomiting, cough, constipation, pyrexia, diarrhea, nausea, abdominal pain, dizziness, and rash. Serious AEs observed were central nervous system problems, bone fractures, and liver problems.

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://tinyurl.com/mtwcrc7r

2. FDA approves larotrectinib for solid tumors with NTRK gene fusions. FDA. November 26, 2018. Accessed April 10, 2025. https://tinyurl.com/4bbjjvea