…the NCCN Panel voted that larotrectinib and entrectinib are both preferred (category 2A) as first-line therapy for patients with NTRK gene fusion-positive metastatic disease.

ROZLYTREK is a kinase inhibitor indicated for the treatment of...Adult and pediatric patients older than 1 month of age with solid tumors that have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion, as detected by an FDA-approved test without a known acquired resistance mutation.

In line with previously reported data, treatment with entrectinib was associated with deep and durable systemic and intracranial responses in pts with advanced NTRK-fp NSCLC.

A total of 22 pts with NTRK-fp NSCLC (NTRK1, n=13; NTRK2, n=3; NTRK3,n=6) were included...Entrectinib showed efficacy in pts with NTRK-fp NSCLC, including those withbaseline CNS metastases...In this updated analysis with longer follow-up and more pts, entrectinibwas associated with deep and durable responses in pts with NTRK-fp NSCLC, includingthose with baseline CNS metastases.

Entrectinib induced clinically meaningful intracranial responses in pts with NTRK-fp or ROS1-fp NSCLC with CNS metastases at baseline. Intracranial ORR, median intracranial DoR and median intracranial PFS for these two cohorts are shown in the table.

Thirteen pts had NTRK-fp NSCLC (NTRK1, n=8; NTRK2, n=1; NTRK3, n=4)….In this updated analysis with longer follow-up, entrectinib was highly active, achieving durable responses in pts with NTRK-fp NSCLC, including pts with baseline CNS metastases.

As of 30 Oct 2018 (additional 5 months’ follow-up), BICR ORR: ROS1+ 79.2% (95% CI 65.9–89.2) and NTRK+ 70.0% (95% CI 34.75–93.33) with complete responses in 5 (9.4%) pts and 1 (10.0%) pt, respectively….In line with the primary data, in pts with ROS1+ and NTRK+ NSCLC after an additional 5 months of follow-up, entrectinib was well tolerated and showed clinically meaningful, durable systemic and intracranial responses.

In total, 20 pts with ROS1-fp NSCLC and 10 pts with NTRK-fp solid tumours (5 salivary, 1 breast, 1 colorectal, 1 NSCLC, 1 sarcoma, 1 thyroid) were efficacy evaluable. For both cohorts, median survival follow-up was 38.6 mos and ORR was 70%....The 24-mos OS rates were 65% (ROS1-fp NSCLC) and 90% (NTRK-fp solid tumours). In pts without baseline CNS mets by investigator, ORR was 76% (ROS1-fp NSCLC; n=13/17) and 75% (NTRK-fp solid tumours; n=6/8). In pts with baseline CNS mets by BICR (3 ROS1-fp; 1 NTRK-fp), one pt (NTRK-fp) had an IC response....Entrectinib showed deep and durable responses and manageable safety in Japanese pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK-fp solid tumours.