Entrectinib Precision Cancer Medicine Targets NTRK, ROS1 or ALK Gene Fusions in

NTRK targeted precision cancer medicines - a new treatment for pediatric and other solid cancers.

by Dr. C.H. Weaver M.D. 6/2019

The Phase I/II study of entrectinib, an investigational medicine, showed responses in all pediatric tumor types harboring neurotrophic tyrosine receptor kinase (NTRK), ROS1 or anaplastic lymphoma kinase (ALK) fusions, including those in the central nervous system.

About Entrectinib

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 ROS 1 gene fusions. It is a selective tyrosine kinase inhibitor designed to inhibit the kinase activity of the TRK A/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 breast, cholangiocarcinoma, colorectal, gynecological, neuroendocrine, non-small cell lung, salivary gland, pancreatic, sarcoma and thyroid cancers.

About the STARTRK-NG study

The STARTRK-NG clinical trial evaluated the safety and effectiveness of entrectinib in 29 children and adolescent cancer patients with no curative first-line treatment option and recurrent or refractory extracranial solid tumors or primary CNS tumors, with or without NTRK, ROS1 or ALK fusions. Eleven children were identified to have cancers with NTRK, ROS1 or ALK fusions.

  • Complete responses were observed in two patients with NTRK and ALK fusions: one with an NTRK fusion-positive primary CNS tumor and one with an ALK fusion-positive inflammatory myofibroblastic tumor. Another complete response was observed in one neuroblastoma patient with an ALK F1174L mutation.
  • Partial responses were observed in nine patients, three unconfirmed at the time of the clinical cut-off date, across NTRK, ROS1 and ALK fusion-positive primary CNS (n=4) and extracranial (n=5) solid tumors.

The FDA recently granted Priority Review for entrectinib for both the treatment of pediatric and adult patients with NTRK fusion-positive, locally advanced or metastatic solid tumors who have either progressed following prior therapies or as an initial therapy when there are no acceptable standard therapies, and for the treatment of people with metastatic ROS1-positive NSCLC.

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