FDA Approves Vitrakvi for NTRK Tumors
Bayer announced that the FDA has granted full approval for Vitrakvi (larotrectinib), a first-in-class TRK inhibitor 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
The regulatory decision was supported by data from three single-arm studies: the phase I LOXO-TRK-14001 (NCT02122913), phase I/II SCOUT (NCT02637687) and phase II 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]). Patients undergoing a surgical resection whose post-operative pathologic assessment showed no viable tumor cells and negative margins were pathological complete responders provided that no other sites of disease were present.
All 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. The major efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as determined by a blinded independent review committee (BIRC) according to RECIST v1.1. Safety was assessed in 444 patients across the three trials.
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%). 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%).
“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."
"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. "This milestone not only benefits patients today but also paves the way for further advancements in NTRK gene therapies in the future."
Citation- 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
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