General Information

Vitrakvi (larotrectinib) is a kinase inhibitor. 

Vitrakvi is specifically indicated for the treatment of adult and pediatric patients with solid tumors that:

• have a neurotrophic receptor tyrosine kinase (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.

Vitrakvi is supplied as both a capsule and an oral solution. The recommended dose regimen is as follows:

Adult and Pediatric Patients with Body Surface Area of at Least 1.0 Meter-Squared:

• Vitrakvi 100 mg orally twice daily, with or without food, until disease progression or until unacceptable toxicity.

Pediatric Patients with Body Surface Area Less Than 1.0 Meter-Squared:

• Vitrakvi 100 mg/m2 orally twice daily, with or without food, until disease progression or until unacceptable toxicity. 

Mechanism of Action

Vitrakvi (larotrectinib) is a kinase inhibitor. Research suggests that the NTRK genes can become abnormally fused to other genes, producing a TRK fusion protein that can lead to the growth and survival of solid tumors in various sites of the body.

Side Effects

Adverse effects associated with the use of Vitrakvi may include, but are not limited to, the following:

• fatigue
• nausea
• dizziness
• vomiting
• increased AST
• cough
• increased ALT
• constipation
• diarrhea

Clinical Trial Results

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. 

The FDA approval of Vitrakvi was based on pooled data across a Phase I adult trial, the Phase II NAVIGATE trial and the Phase I/II pediatric SCOUT trial (N=55). In pooled study results, Vitrakvi demonstrated an overall response rate (ORR) of 75% by blinded independent review committee, with 22% of patients achieving a complete response and 53% achieving a partial response across various tumor types, including soft tissue sarcoma, salivary gland, infantile fibrosarcoma, thyroid, lung, melanoma, colon, GIST, cholangiocarcinoma, appendix, breast and pancreas. Seventy-three percent of responding patients (N=41) had a duration of response (DOR) lasting six months or greater at the time of data cut-off. Median DOR (range 1.6+, 33.2+) and progression-free survival (PFS) had not been reached at the time of analysis. Median time to response was 1.84 months.