Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced 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 tumors (objective response rate; ORR) in 77.4 percent of people with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). In addition, entrectinib demonstrated a durable response of more than two years (duration of response [DoR] = 24.6 months). Importantly, entrectinib was shown to shrink tumors in more than half of people with cancer in the central nervous system (CNS) (intracranial ORR: 55 percent). The safety profile of entrectinib was consistent with that seen in previous analyses, and no new safety signals were identified. Based on the integrated analysis of these studies, Genentech plans to submit these data to global health authorities.
“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 tumors have spread to the central nervous system,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “We are also investigating entrectinib in NTRK fusion-positive tumors 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 percent of people with NSCLC. NSCLC is the most common type of lung cancer and accounts for 85 percent of all lung cancer diagnoses. Approximately 30-40 percent of people with ROS1-positive NSCLC have brain metastases at time of diagnosis.
These ROS1 results will be presented at the 2018 World Conference on Lung Cancer (WCLC) in Toronto, Canada on Monday, September 24 from 10:30 – 10:40 a.m. EDT (Abstract 13903), and featured in the WCLC press program on Monday, September 24 from 9:45 – 10:30 a.m. EDT. Follow Genentech on Twitter via @Genentech 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. The studies enrolled people across 15 countries and more than 150 clinical trial sites.
STARTRK-2 is a Phase II, global, multicenter open-label basket study in people with solid tumors that harbor an NTRK1/2/3 or ROS1 gene fusion. The primary endpoint is ORR. Secondary outcome measures include DoR, time to response, clinical benefit rate, intracranial tumor response, progression-free survival (PFS), CNS PFS and overall survival (OS).
STARTRK-1 is a Phase I, multicenter, open-label dose escalation study of a daily continuous dosing schedule in people with solid tumors with NTRK1/2/3 or ROS1 gene fusions in the U.S. and South Korea. The trial assessed the safety and tolerability of entrectinib via a standard dose escalation scheme and determined the recommended Phase II dose.
ALKA is a Phase I, multicenter, open-label dose escalation study of an intermittent and continuous entrectinib dosing schedule in people with advanced or metastatic solid tumors with ROS1 gene fusions in Italy.
Adverse events were consistent with previous data. The most commonly reported adverse events include those affecting the nervous system, as well as constipation, altered sense of taste (dysgeusia), and fatigue.
Entrectinib (RXDX-101) is an investigational, oral medicine in development for the treatment of locally advanced or metastatic solid tumors that harbor NTRK1/2/3 or ROS1 gene fusions. It is a selective 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. Entrectinib can block ROS1 and NTRK kinase activity and may result in the death of cancer cells with ROS1 or NTRK gene fusions. Entrectinib is being investigated across a range of solid tumor types, including non-small cell lung cancer, pancreatic cancer, sarcomas, thyroid cancer, salivary cancer, gastrointestinal stromal tumors (GIST) and cancers of unknown primary (CUP).