By Mark Terry
Ignyta updated results from its STARTRK-2 clinical trial of entrectinib in non-small cell lung cancer (NSCLC) today, causing company stock to jump about five percent before settling down.
Entrectinib is an investigational, CNS-active, selective tyrosine kinase inhibitor under development for tumors that have NTRK fusions or ROS1 fusions. In the interim data, entrectinib showed a 78 percent confirmed ORR and a 69 percent confirmed ORR, using separate metrics, in 32 patients with locally advanced or metastatic non-small cell lung cancer that harbored ROS1 fusions. The median duration of response (mDOR) was 28.6 months for these patients, with a median progression free survival (mPFS) of 29.6 months.
“Based on these data, we believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC,” said Jonathan Lim, Ignyta’s chairman and chief executive officer, in a statement. “The extended duration of response and progression free survival times observed in these interim data are particularly compelling, and we believe may be driven by entrectinib’s CNS activity. Entrectinib was designed to cross the blood-brain barrier, allowing it to both address preexisting CNS lesions and have the potential to prevent or delay the onset of metastases to the brain, a common site of progression, particularly in NSCLC.”
Adverse events were Grade 1-2 and reversible, with only three percent of patients unable to continue due to treatment-related side effects. The most common side effects were dysgeusia (changes in taste sensations), fatigue, constipation, dizziness, and increased weight. There were no Grade 4 or 5 side effects. The most common Grade 3 side effects were increased weight, anemia, and fatigue.
“ROS1 fusions occur in approximately two percent of all cases of NSCLC and, given the propensity for these tumors to metastasize to the brain, the CNS activity of entrectinib is a critical differentiating feature of the compound and may be contributing to the impressive duration and progression free survival it has demonstrated thus far,” said Myung-Ju Ahn, professor in the Department of Hematology and Oncology at the Samsung Medical Center in Seoul, South Korea, and study author, in a statement.
The compound has also shown promising preliminary antitumor activity across NTRK-positive solid tumors. This has resulted in entrectinib receiving breakthrough therapy designation from the U.S. Food and Drug Administration (FDA) and PRIME designation from the European Medicines Agency (EMA). Based on guidance from the FDA, Ignyta is on track for dual new drug application (NDA) submissions in both the NTRK tissue-agnostic and the ROS1-positive NSCLC indications next year.
“We are pleased and grateful that the EMA has accepted entrectinib into its PRIME program, which is analogous to the Breakthrough Therapy Designation from the U.S. FDA that entrectinib received earlier this year,” Lim said in a statement yesterday. “This PRIME designation recognition is the result of the efforts of Ignyta’s team to ensure that entrectinib development was global in nature from its earliest days, and further validates the broad potential of entrectinib as a novel treatment for patients, regardless of age, with NTRK-positive tumors, a group of cancers for which there currently is no approved treatment. We look forward to collaborating with the EMA, as well as other global regulatory authorities, on the accelerated assessment of entrectinib with the goal to provide a new therapy for patients in need.”
Ignyta stock is currently trading for $16.02. Shares traded on Wednesday, May 3 for $6.15 and on Monday, Oct. 16 for $13.40. Shares jumped to $17.50 early this morning after the news was released, but has since settled to around $16 per share.