CHMP recommends larotrectinib to treat solid tumors with a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency has recommended Bayer’s precision oncology treatment larotrectinib for marketing authorization in the European Union (EU). The recommended indication is treatment of adult and pediatric patients with solid tumors that display a Neurotrophic Tyrosine Receptor Kinase (NTRK) gene fusion, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have no satisfactory treatment options. The final decision of the European Commission on the marketing authorization is expected in the coming months.

Larotrectinib, a first-in-class oral TRK inhibitor specifically developed to treat tumors that have an NTRK gene fusion, will be the first treatment to receive a tumor-agnostic indication in the EU. Larotrectinib is already approved in the U.S. as well as in Brazil and Canada.

The CHMP recommendation is based on pooled clinical trial data of 102 patients (93 patients from the primary analysis population and an additional 9 patients with primary central nervous [CNS] tumors) across the Phase I trial of adult patients, the Phase II NAVIGATE trial in adult and adolescent patients and the Phase I/II pediatric SCOUT trial, showing a high response rate with durable and rapid responses for larotrectinib. Results in the primary analysis population demonstrate an overall response rate (ORR) of 72% (95% CI: 62, 81), including a 16% complete response (CR) rate and a 55% partial response (PR) rate. In an additional analysis including primary CNS patients, the ORR was 67% (95% CI: 57, 76), including a 15% CR, and a 51% PR. In the pooled primary analysis set, the median duration of response was not reached at time of analysis with responses ranging from 1.6+ to 38.7+ months and 75% of patients having a duration of response of 12 months or longer. Eighty-eight percent (95% CI: 81, 95) of patients treated were alive one year after the start of therapy. Median progression free survival had not been reached at the time of analysis.

The safety of larotrectinib was evaluated in 125 patients with an NTRK gene fusion. The majority of adverse events (AEs) were grade 1 or 2; three percent of patients had to stop therapy due to treatment-emergent AEs. Dose reduction in the target population (n=125) was reported in 19 (15%) patients including 10 (8%) due to AEs. The majority of AEs leading to dose reduction occurred within the first three months of treatment.