On September 24, 2018 Roche (SIX: RO, ROG; OTCQX: RHHBY) reported results for its investigational medicine entrectinib, from an integrated analysis of the pivotal phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA trials, which showed that entrectinib shrank tumours (objective response rate; ORR) in 77.4% of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) (Press release, Hoffmann-La Roche, SEP 24, 2018, View Source [SID1234529661]).1 In addition, entrectinib demonstrated a durable response of more than two years (duration of response [DoR] = 24.6 months).1 Importantly, entrectinib was shown to shrink tumours in more than half of people with cancer in the central nervous system (CNS) (intracranial ORR: 55.0%).1 The safety profile of entrectinib was consistent with that seen in previous analyses, and no new safety signals were identified.1 Based on the integrated analysis of these studies, Roche plans to submit these data to global health authorities.
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"These results show the potential of precision medicines to deliver tailored and effective treatment options for people with non-small cell lung cancer, including those whose tumours have spread to the central nervous system," said Sandra Horning, MD, Roche’s Chief Medical Officer and Head of Global Product Development. "We are also investigating entrectinib in NTRK fusion-positive tumours across several different cancer types, and look forward to presenting those results in the near future."
ROS1 gene fusions have been identified in 1-2% of people with NSCLC.2 NSCLC is the most common type of lung cancer and accounts for 85% of all lung cancer diagnoses.3 Approximately 30-40% of people with ROS1-positive NSCLC have brain metastases at time of diagnosis.4
These ROS1 results will be presented at the 2018 World Conference on Lung Cancer (WCLC) in Toronto, Canada on Monday, 24 September 2018, from 10:30 – 10:40 a.m. EDT (Abstract 13903), and featured in the WCLC press programme on Monday, 24 September, from 9:45 – 10:30 a.m. EDT. Follow Roche on Twitter via @Roche and keep up to date with WCLC 2018 congress news and updates by using the hashtag #WCLC2018.
About the integrated analysis
The integrated analysis included data from 53 people with ROS1-activating gene fusions from the phase II STARTRK-2, phase I STARTRK-1 and phase I ALKA trials.1 The studies enrolled people across 15 countries and more than 150 clinical trial sites.1
STARTRK-2 is a phase II, global, multicentre, open-label basket study in people with solid tumours that harbour an NTRK1/2/3 or ROS1-positive gene fusion.5 The primary endpoint is ORR.5 Secondary outcome measures include DOR, time to response, clinical benefit rate, intracranial tumour response, progression-free survival (PFS), CNS PFS and overall survival (OS).5
STARTRK-1 is a phase I, multicentre, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumours with NTRK1/2/3 or ROS1 gene fusions in the US and South Korea.6 The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended phase II dose.6
ALKA is a phase I, multicentre, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumours with ROS1 gene fusions in Italy.7
Adverse events were consistent with previous data.1 The most commonly reported adverse events include those affecting the nervous system, as well as constipation, altered sense of taste (dysgeusia) and fatigue.1
About entrectinib
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumours that harbour NTRK1/2/3 or ROS1 gene fusions. It is a selective, CNS-active tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRKA/B/C and ROS1 proteins, whose activating fusions drive proliferation in certain types of cancer.8,9 Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions.8,9 Entrectinib is being investigated across a range of solid tumour types, including non-small cell lung cancer, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumours (GIST) and cancers of unknown primary (CUP).5-7
Entrectinib has been granted Breakthrough Therapy Designation (BTD) by the US Food and Drug Administration (FDA); Priority Medicines (PRIME) designation by the European Medicines Agency (EMA); and Sakigake designation by the Japanese health authorities for the treatment of NTRK-positive, locally advanced or metastatic solid tumours in adult and pediatric patients who have either progressed following prior therapies or have no acceptable standard therapies.7
About ROS1-positive non-small cell lung cancer (NSCLC)
ROS1 is a tyrosine kinase, which plays a role in controlling how cells grow and proliferate. When a ROS1 gene fusion occurs, cancer cells grow and proliferate in an uncontrolled manner. Blocking this abnormal signalling can cause tumour cells to shrink or die.2
ROS1 gene fusions account for 1-2% of non-small-cell lung cancer (NSCLC).2 Lung cancer is the leading cause of cancer-related death across the world.10 Each year, more than one and a half million people die as a result of the disease globally, equating to more than 4,000 deaths every day.10 NSCLC is the most common type of lung cancer and accounts for 85% of all lung cancer diagnoses.3 While the ROS1 gene fusion can be found in any patient with NSCLC, young never-smokers with NSCLC have the highest incidence of ROS1 gene fusions.2