Roche has announced that the European Commission has granted conditional marketing authorisation for Rozlytrek (entrectinib) 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, who have a disease that is locally advanced, metastatic or where surgical resection is likely to result in severe morbidity, and who have not received a prior NTRK inhibitor, who have no satisfactory treatment options. The European Commission has also approved Rozlytrek for the treatment of adults with ROS1-positive, advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.
“We are excited to announce the approval of Rozlytrek in Europe for two indications, bringing patients with NTRK and ROS1 gene fusions a new effective treatment even when their cancer has spread to the brain,” said Levi Garraway, Roche’s Chief Medical Officer and Head of Global Product Development.
The approval is 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. These studies demonstrate that Rozlytrek has durable responses across several NTRK gene fusion-positive solid tumours, including sarcoma, non-small cell lung, salivary MASC, secretory and non-secretory breast, thyroid, colorectal, neuroendocrine, pancreatic, ovarian, endometrial carcinoma, cholangiocarcinoma, gastrointestinal cancers and neuroblastoma, as well as ROS1-positive NSCLC.
Results showed:
- Rozlytrek shrank tumours in more than half of people with NTRK fusion-positive, locally advanced or metastatic solid tumours (overall response rate [ORR] = 63.5 per cent; N=74), and objective responses were observed across 13 tumour types (median duration of response [DoR] = 12.9 months [9.3 months – not reached], N=21 out of 47 patients defined by ORR).
- In ROS1-positive, advanced NSCLC, Rozlytrek shrank tumours in 73.4 per cent of people with the disease (ORR; N=94 with a minimum of 12 months follow up), with a median DoR of 16.5 months (14.6 – 28.6 months). In a group of 161 patients with a minimum of 6 months follow up, including 29 per cent of patients with central nervous system (CNS) metastases at baseline, ORR was observed to be 67.1 per cent.
- Objective responses to Rozlytrek were seen in people with CNS metastases at baseline, with an intracranial ORR of 62.5 per cent and 79.2 per cent in both NTRK and ROS1 populations, respectively.
- In paediatric patients, Rozlytrek shrank tumours (ORR) in all children and adolescents who had NTRK gene fusions (N=5), with two achieving a complete response (CR). Two patients with primary high-grade tumours in the CNS had objective responses, including one patient with a CR.1 Rozlytrek was well tolerated.
- The most common adverse reactions (≥20 per cent) with Rozlytrek were fatigue, constipation, altered sense of taste (dysgeusia), swelling (oedema), dizziness, diarrhoea, nausea, nervous system disorders (dysaesthesia), shortness of breath (dyspnoea), anaemia, increased weight, increased blood creatinine, pain, cognitive disorders, vomiting, cough, and fever (pyrexia).
Rozlytrek has been granted Priority Medicines (PRIME) designation by the EMA for the treatment of NTRK fusion-positive, locally advanced or metastatic solid tumours in adult and paediatric patients who have either progressed following prior therapies or who have no acceptable standard therapies. NTRK gene fusions have been identified in a range of solid tumour types, and are present in up to 90 per cent of some rare cancer types and less than one per cent of other more common tumours, including lung and colorectal. ROS1 gene fusions account for one to two per cent of NSCLC, the most common type of lung cancer that accounts for up to 85 per cent of all diagnoses.
Biomarker testing for these fusions is the most effective way to identify people who are most eligible for treatment with Rozlytrek. Roche, in conjunction with Foundation Medicine, is trying to develop a companion diagnostic that will help identify people with NTRK and ROS1 gene fusions.