On March 30, 2017 Ignyta, Inc. (Nasdaq: RXDX), a biotechnology company focused on precision medicine in oncology, reported data demonstrating the successful treatment with entrectinib – Ignyta’s investigational, orally available, CNS-active tyrosine kinase inhibitor targeting tumors that harbor TRK, ROS1 or ALK fusions – of a patient with a primary brain tumor harboring an NTRK1 fusion (Press release, Ignyta, MAR 30, 2017, View Source [SID1234518323]).

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The study, exploring genetic alterations associated with glioneuronal tumors, was led by researchers at Massachusetts General Hospital and was published in Precision Oncology. Researchers discovered novel oncogenic fusions involving members of the NTRK gene family in three out of 26 patients evaluated, and reported that in a patient with a BCAN-NTRK1 fusion, treatment with entrectinib resulted in a 60 percent regression in tumor size and the resolution of clinical symptoms that was maintained for 11 months on treatment. Entrectinib is currently being studied in a registration-enabling Phase 2 clinical trial known as STARTRK-2.

"We are pleased to see the CNS activity of entrectinib demonstrated in this peer-reviewed publication in Precision Oncology, which highlights the need for CNS-active compounds to effectively treat CNS neoplasms, as well as other solid tumors with a propensity to metastasize to the brain," said Jonathan Lim, M.D., Chairman and CEO of Ignyta. "This robust activity of entrectinib in a patient with a primary brain tumor builds on the rapid and durable anti-tumor activity we’ve seen with this compound across other TRK, ROS1, or ALK solid tumors across multiple histologies and complements the 71% RECIST ORR (five out of seven patients) demonstrated in patients with extracranial tumors that had metastasized to the brain in our Phase 1 studies. Entrectinib is the only TRK inhibitor to have demonstrated RECIST responses in patients with CNS disease and the only TRK inhibitor to have a peer-reviewed publication on its activity in primary brain tumors."

Data presented in the study characterized a cohort of 26 glioneuronal tumors, which identified, through in-depth genomic analysis, BRAF mutations in 34 percent of tumors and oncogenic fusions in 30 percent of tumors. Further, researchers identified three tumors in the cohort that contained fusions involving members of the NTRK gene family, including one patient harboring a BCAN-NTRK1 fusion. Based on previous clinical results, therapeutic intervention for the patient harboring the NTRK1 fusion was pursued, and entrectinib was selected due to its CNS activity. Following subtotal surgical resection and confirmation of the tumor’s specific genetic alteration, the patient was enrolled in the Phase 1 dose-escalation trial of entrectinib (NCT02097810). The patient received entrectinib daily for 11 months and experienced lower extremity edema as the only documented side effect related to therapy. Analysis after nine months of treatment showed a 60 percent reduction in the size of the tumor, as well as improvement in vision-related symptoms. The patient was taken off of treatment after 11 months due to a gradual worsening of vision and tumor size. Based on the results of the study, we believe NTRK fusions should be considered an actionable target for glioneuronal tumor treatment.