FDA Approves Larotrectinib for NTRK Fusion-Positive Solid Tumors

Median DOR for patients taking larotrectinib was 43.3 months (95% CI, 32.5-NE).

The FDA approved larotrectinib (Vitrakvi) for use in adult and pediatric patients who have neurotrophic receptor tyrosine kinase (NTRK) gene fusion-positive solid tumors and no known acquired resistance mutation, where tumors are metastatic or where resection will likely cause severe morbidity, and have no appropriate alternative treatments or have progressed after treatment, per an announcement from Bayer.

The first-in-class oral tropomyosin receptor kinase (TRK) inhibitor displayed clinically meaningful and durable response in several NTRK fusion-positive solid tumors. The approval is based on results from multicenter, open-label, single-arm clinical trials LOXO-TRK-14001 (NCT02122913), SCOUT (NCT02637687), and NAVIGATE (NCT02576431).

Larotrectinib was granted accelerated approval by the FDA for the same indication in November 2018.

“This first full approval of an NTRK inhibitor by the FDA represents the culmination of research and dedication by the Bayer team,” noted Chandra Goda, executive director and Vitrakvi brand lead at Bayer, in the news release. “This milestone reinforces Bayer's commitment to delivering innovative solutions that address the unique needs of patients and their families.”

Efficacy Across Trials

Primary end points for all 3 trials were overall response rate (ORR) and duration of response (DOR), as assessed with RECIST v1.1 by a blinded independent review committee.

Efficacy results pooled from the trials found an ORR of 60% (95% CI, 55%-65%). Rate of complete response (CR) and partial response (PR) were 24% and 36%, respectively. Of those who demonstrated CR, 5% showed pathological complete response.

Participants who underwent surgical resection with negative margins and no viable tumor cells found in post-operative pathologic assessment experienced CR as long as no other disease sites were detectable.

Median DOR for patients taking larotrectinib was 43.3 months (95% CI, 32.5-not evaluable [NE]).

Safety of Larotrectinib

The safety of larotrectinib was evaluated in 444 patients across the trials.

Including lab abnormalities, the most frequent adverse events (AEs), occurring in at least 20% of patients taking larotrectinib were increased AST (62%), increased ALT (61%), anemia (45%), hypoalbuminemia (44%), musculoskeletal pain (41%), increased alkaline phosphatase (40%), leukopenia (37%), lymphopenia (35%), neutropenia (34%), hypocalcemia (32%), fatigue (31%), vomiting (30%), cough (29%), constipation (27%), pyrexia (26%), diarrhea (26%), nausea (25%), abdominal pain (24%), dizziness (22%), and rash (21%).

Serious AEs included central nervous system issues, bone fractures, and liver issues.

More on Larotrectinib

Larotrectinib is engineered to inhibit the TRK protein family, which included TRKA, TRKB, and TRKC. The inhibitor displayed anti-tumor activity in cells with overexpression of TRK protein, constitutive activation of TRK proteins caused by gene fusions, or deletion of a protein regulatory domain in in vitro and in vivo tumor models.

“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 and CEO, LUNGevity Foundation, in the news release. “This milestone not only benefits patients today but also paves the way for further advancements in NTRK gene therapies in the future.”

Reference

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. 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