FDA Grants Full Approval to Bayer’s Vitrakvi for NTRK Gene Fusion-Positive Solid Tumors

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The FDA has granted full approval to Bayer’s Vitrakvi (larotrectinib), a first-in-class NTRK inhibitor, for the treatment of adult and pediatric patients with NTRK gene fusion-positive solid tumors. The treatment is now indicated for patients whose tumors are metastatic, difficult to surgically remove, or have progressed following prior treatment, with no satisfactory alternative therapies available. Approval was based on positive results from three clinical trials in patients with unresectable or metastatic NTRK fusion-positive solid tumors. The FDA initially granted Vitrakvi with accelerated approval for this indication in 2018, based on a favorable overall response rate (ORR) and duration of response (DOR) data.^1,2

“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, in a press 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."

The multicenter, open-label, single-arm LOXO-TRK-14001, SCOUT, and NAVIGATE trials included a total of 339 patients. All participants had either experienced progression following systemic therapy or who would have needed surgery to treat locally advanced disease. This approach targeted individuals with limited treatment alternatives or those for whom surgical intervention carried substantial challenges. The dual primary endpoints of the trials were ORR and DOR, as assessed by a blinded independent review committee.

Pooled results from all three trials showed a 60% ORR, including a 24% complete response (CR) rate and a 36% partial response rate, and a median DOR of 43.3 months. Among patients who achieved a CR, 5% were classified as having a pathological complete response, defined as the absence of viable tumor cells and negative surgical margins, with no evidence of disease elsewhere.

Common adverse events (AEs) included 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 included central nervous system (CNS) issues, bone fractures, and liver problems. CNS issues, such as cognitive impairment, mood disorders, dizziness, and sleep disturbances, were reported in 40.3% of patients, with 3.8% experiencing these at a grade 3 or 4 severity level.¹

According to a study published in NPJ Precision Oncology, NTRK gene fusions occur in approximately 0.3% of all solid tumors, though prevalence varies by tumor type. In rare cancers, such as secretory breast carcinoma and mammary analogue secretory carcinoma of the salivary gland, the prevalence exceeds 90%.³

Genentech, a subsidiary of Roche, estimates that NTRK fusions may be present in 1,500 to 5,000 patients annually across children, adolescents, and adults, depending on cancer type. In pediatric populations, NTRK gene fusions are most commonly found in CNS tumors, such as gliomas, as well as melanoma, soft-tissue sarcomas, inflammatory myofibroblastic tumors, congenital infantile fibrosarcoma, and mesoblastic nephroma.⁴

"The full approval of Vitrakvi by the FDA is a welcome step forward, solidifying its place as a treatment option for patients with NTRK gene fusion-positive cancers," said Andrea Ferris, president, CEO, LUNGevity Foundation, in the press release. "This milestone not only benefits patients today but also paves the way for further advancements in NTRK gene therapies in the future."

References

1. U.S. FDA Grants Full Approval of VITRAKVI® (larotrectinib) for Adult and Pediatric Patients with NTRK Gene Fusion-Positive Solid Tumors. Businesswire. 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 Vitrakvi® (larotrectinib), the First Ever TRK Inhibitor, for Patients with Advanced Solid Tumors Harboring an NTRK Gene Fusion(1,2). PR Newswire. November 26, 2018. Accessed April 10, 2025. https://www.prnewswire.com/news-releases/fda-approves-vitrakvi-larotrectinib-the-first-ever-trk-inhibitor-for-patients-with-advanced-solid-tumors-harboring-an-ntrk-gene-fusion1-2-300755551.html

3. Genomic context of NTRK1/2/3 fusion-positive tumours from a large real-world population. Nature. July 20, 2021. Accessed April 10, 2025. https://www.nature.com/articles/s41698-021-00206-y#:~:text=NTRK%20gene%20fusions%20occur%20in%20~0.3%%20of,secretory%20carcinoma%20of%20the%20salivary%20gland%20(MASC)7%2C8.

4. Neurotrophic Tyrosine Receptor Kinase (NTRK) Fusion-Positive Cancers. Genentech. Accessed April 10, 2025. https://www.gene.com/patients/disease-education/neurotrophic-tyrosine-receptor-kinase