INNs facilitate the identification of active pharmaceutical ingredients, and each INN is a globally recognized unique name.
As a novel, orally available, selective tyrosine kinase inhibitor of the Trk family of tyrosine kinase receptors (TrkA, TrkB and TrkC), ROS1 and ALK proteins, entrectinib is designed as a targeted therapeutic candidate to treat patients with cancers that harbor activating alterations to TrkA, TrkB, TrkC, ROS1 or ALK.
Entrectinib has demonstrated in vivo antitumor activity against various TrkA, ROS1 or ALK-driven mouse xenograft models of different human cancers, and has demonstrated oral bioavailability and been observed to efficiently cross the blood brain barrier in three animal species.
Entrectinib is currently in two Phase I/II clinical trials, the STARTRK-1 trial and the ALKA-372-001 trial. The company presented interim results from the ALKA-372-001 study in September 2014 at the ESMO annual meeting. The interim findings at such date showed:
- No dose-limiting toxicities were observed, and only one Grade 3 or higher possibly drug-related adverse event was observed (Grade 3 fatigue, which subsided with dose reduction);
- Eight patients remained on active treatment across the three dosing schedules, with four patients having received 9 to 21 cycles of treatment;
- Entrectinib demonstrated a complete response in a patient with ROS1-positive non-small cell lung cancer (NSCLC);
- Entrectinib demonstrated five partial responses, in patients with three different cancer histologies (colorectal cancer, NSCLC and neuroblastoma) and in patients with each of TrkA, ROS1 and ALK alterations; and
- Entrectinib demonstrated prolonged stable disease in two patients: one with ALK-positive NSCLC and one with ROS1-positive pancreatic cancer.