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.

entrectinib (Rozlytrek) is accepted for use within NHSScotland....as monotherapy for the treatment of adult and paediatric patients 12 years of age and older with solid tumours expressing a neurotrophic tyrosine receptor kinase (NTRK) gene fusion

Rozlytrek is a cancer medicine. It can be used for treating patients from 12 years of age with solid tumours (cancer growths) that have a genetic abnormality called NTRK gene fusion.

ROZLYTREK is a kinase inhibitor indicated for the treatment of...Adult and pediatric patients 12 years of age and older with solid tumors that...have a neurotrophic tyrosine receptor kinase (NTRK) gene fusion without a known acquired resistance mutation

Recommendation...Entrectinib is an option for treating adults and adolescents aged ≥12 years with metastatic or unresectable NTRK fusion-positive solid tumours that have progressed in spite of standard-of-care treatment…

...entrectinib and larotrectinib are recommended as second-line or subsequent treatment options for patients with NTRK gene fusion-positive solid tumors…

Roche...announced that the US Food and Drug Administration (FDA) has accepted the company’s New Drug Applications (NDAs) and granted Priority Review for entrectinib for the treatment of adult and paediatric patients with neurotrophic tropomyosin receptor kinase (NTRK) fusion-positive locally advanced or metastatic solid tumors...

Ignyta, Inc...announced that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation (BTD) to entrectinib for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumors...

...- Part B: Primary brain tumors with NTRK1/2/3 or ROS1 gene fusions; gene fusions are defined as those predicted to translate into a fusion protein with a functional TRKA/B/C or ROS1 kinase domain, without a concomitant second oncodriver as determined by a nucleic acid-based diagnostic testing method...

Adults with measurable, locally advanced/metastatic NTRK-fp solid tumours and ≥12 months’ follow-up from first on-study scan, who received ≥1 dose of entrectinib, were efficacy evaluable….Median survival follow-up was 38.7 months. ORR was 62.4% (95% CI 55.2–69.2); the table shows responses in histologies with n>10. Median DoR was 29.4 months (95% CI 17.2–36.8). Median PFS and OS were 15.7 months (95% CI 13.7–22.9) and 38.2 months (95% CI 28.6–56.5), respectively....In this updated analysis, entrectinib was well tolerated and continued to induce clinically meaningful responses in pts with NTRK-fp solid tumours.

This updated analysis with longer follow-up provides further evidence that entrectinib is associated with deep and durable responses in Chinese pts with NTRK-fp solid tumours or ROS1-fp NSCLC.

Median survival follow-up was 30.6 months. ORR was 61.3% (n = 92/150; 95% CI: 53.1–69.2), including 25 complete responses. Responses were observed in all tumor types with n>1 (Table). Median DoR, PFS and OS were 20.0 months (95% CI 13.2–31.1), 13.8 months (95% CI 10.1–20.0), and 37.1 months (95% CI 27.2–not estimable [NE]), respectively. In pts with and without investigator-assessed baseline CNS metastases (n = 31 / n = 119), ORR was 61.3% (95% CI 42.2–78.2) and 61.3% (95% CI 52.0–70.1) respectively. In this updated analysis, entrectinib continued to demonstrate deep and durable responses and was well tolerated in pts with NTRK-fp solid tumors with or without baseline CNS metastases.

Phase 1, dose escalation of oral, once-daily entrectinib, enrolled patients aged <22 years with solid tumors with/without target NTRK1/2/3, ROS1, or ALK fusions….In patients with fusion-positive tumors, ORR was 57.7% (95% CI 36.9-76.7)….Entrectinib resulted in rapid and durable responses in pediatric patients with solid tumors harboring NTRK1/2/3 or ROS1 fusions.

Adult Chinese pts with ROS1- and TRK- TKI-naïve, ROS1-fp locally advanced/metastatic NSCLC or NTRK-fp solid tumours were enrolled....In Chinese pts with locally advanced/metastatic ROS1-fp NSCLC or NTRK fp solid tumours, with or without baseline CNS metastases, entrectinib induced deep and durable responses.

Patients with locally advanced/metastatic NTRK fusion-positive solid tumors...Median follow-up was 25.8 months; 61.2% of patients had a complete (n = 19) or partial response (n = 55). Median DoR was 20.0 months (95% CI, 13.0-38.2); median PFS 13.8 months (95% CI, 10.1-19.9)...With additional clinical experience, entrectinib continues to demonstrate durable systemic and intracranial responses, and can address the unmet need of a CNS-active treatment in patients with NTRK fusion-positive solid tumors.

Among the 89 patients with evaluable efficacy data included in the exposure-efficacy analysis, 73% (65/89) achieved a complete or partial response….Model-described tumor shrinkage rates were 8-12 times greater than growth rates in both ROS-1-positive NSCLC patients and NTRK fusion-positive solid tumor patients. Entrectinib exposure distribution was similar in responders and non-responders....These analyses supported that entrectinib at 600 mg/day provides an acceptable benefit-risk ratio in adults with NTRK-, ROS1-, or ALK-positive tumors, considered as rare disease.

Median BICR DoR was 20.0 months (95% CI 13.0–38.2). Median BICR PFS was 13.8 months (95% CI 10.1–19.9); median OS was 33.8 months (95% CI 23.4–46.4)....In this updated analysis, in a larger cohort of patients with locally advanced/metastatic NTRK-fp solid tumours and longer follow-up, entrectinib continued to have clinically meaningful efficacy and was well tolerated.

SA-PRO populations comprised patients with NTRK fusion-positive solid tumours (N = 88) or ROS1 fusion-positive non-small-cell lung cancer (N = 180) who received one or more doses of entrectinib...Both cohorts reported low-to-moderate symptom burden at baseline, which was maintained or trended towards clinically meaningful improvement.

In patients with NTRK-positive solid tumours, the objective response rate (ORR) was 63.5% [95% confidence interval (CI) 51.5% to 74.4%] and the median duration of response (DOR) was 12.9 months (95% CI 9.3-not estimable)....Entrectinib induced clinically meaningful and durable objective responses in patients with NTRK-fusion positive solid tumours...

...74 pts with NTRK+ solid tumours...data demonstrate similar responses to entrectinib in pts with ROS1+ NSCLC and NTRK+ solid tumours regardless of prior therapy exposure, supporting its use irrespective of number of prior lines of systemic therapy; ORR was >70% in pts receiving entrectinib as first-line therapy. Table: 540P

In this updated analysis, including more pts and longer follow-up, entrectinib continued to demonstrate clinically meaningful responses in pts with NTRK-fp solid tumors…

Entrectinib induced durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours…These results show that entrectinib is a safe and active treatment option for patients with NTRK fusion-positive solid tumours.

In this multicenter, pooled analysis of global clinical trials, entrectinib was well tolerated overall and induced clinically meaningful, durable systemic responses in pts with NTRK-fp solid tumors, type agnostic, with and without CNS disease.