Investigational ROS1 inhibitor

ROS1 oncogenic fusions are observed in ~1-2% non-small cell lung cancer (NSCLC) patients (J Thorac Oncol 2017). It is estimated there are more than 21,000 newly diagnosed patients with ROS1-positive NSCLC in the United States, China and Europe each year. ROS1 fusions are observed in several other cancers such as cholangiocarcinoma, glioblastoma, ovarian, gastric, and colorectal cancers. The incidence of CNS metastasis in ROS1-positive NSCLC patients at the time of diagnosis ranges from 20% to mid-30%, and can be as high as mid-50% range post-crizotinib treatment (Lung Cancer 2019).

There are limited treatment options for people with ROS1-positive NSCLC. Crizotinib and entrectinib are first-generation ROS1 tyrosine kinase inhibitors that are FDA-approved for advanced ROS1-positive NSCLC. There are currently no FDA approved therapies for patients who do not respond to these first-generation ROS1 inhibitors or for patients who have developed resistance to the available therapies and whose disease has progressed. Resistance to first-generation ROS1 inhibitors will ultimately occur with on-target resistance such as with acquired ROS1 G2032R mutations, one of the most common treatment-resistant mutations.

Taletrectinib is an oral, potent, brain penetrant, selective, next-generation potential best-in-class ROS1 inhibitor being evaluated for the treatment of ROS1-positive NSCLC in people who have not previously received treatment with a tyrosine kinase inhibitor (TKI-naïve), as well as people who have previously received treatment with a TKI.

Taletrectinib is designed to overcome some of the challenges with existing therapies, including reducing TRKB-related neurological adverse events through selective inhibition of ROS1 over TRKB, penetrating the blood-brain barrier to address brain metastases, and addressing treatment resistance in tumors (Nature Communications 2019).

Results from the TRUST-I Phase 2 trial (NCT04395677) were presented at ELCC 2023.

Interim results from the global pivotal TRUST-II Phase 2 trial (NCT04919811) were presented at ESMO 2023.