Entrectinib (Rozlytrek) has been cleared for the treatment of adults with ROS1-positive, metastatic non-small cell lung cancer (NSCLC), by the US FDA.
The FDA has also granted accelerated approval to entrectinib for the treatment of adult and paediatric patients 12 years of age and older with solid tumours that have a neurotrophic tyrosine receptor 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 progressed following treatment or have no satisfactory alternative therapy.
It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusion.
These approvals are based on results from the integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA-372-001 trials, and data from the phase I/II STARTRK-NG study.
In the integrated analysis, entrectinib was studied in several solid tumour types, including breast, cholangiocarcinoma, colorectal, gynaecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.
In ROS1-positive, metastatic NSCLC, the drug shrank tumours in 78% of people with the disease (overall response rate [ORR]; N=51) and the duration of response (DoR) ranged from 1.8 to 36.8+ months (N=40 out of 51).
The drug also shrank tumours in more than half of people with NTRK gene fusion-positive, locally advanced or metastatic solid tumours (ORR=57%; N=54), and objective responses were observed across 10 tumour types (DoR ranged from 2.8 to 26.0+ months; N=31 out of 54).1 Objective responses to entrectinib were seen in people with central nervous system (CNS) metastases at baseline, Roche said.