The combined analysis of 134 patients with ROS1 fusion-positive NSCLC who participated in phase 1/2 trials showed entrectinib to have strong intracranial efficacy be well-tolerated with a manageable safety profile.
Why this matters
Brain metastases are frequent in patients with ROS1 fusion-positive NSCLC. Entrectenib is a potent inhibitor of ROS1 and was designed to penetrate the brain. It achieved therapeutic levels in multiple intracranial tumor models.
Updated and integrated safety and efficacy data from 3 phase 1/2 studies with entrectinib in 134 patients with locally advanced/metastatic ROS1 fusion-positive NSCLC (ALKA-372-001, STARTRK-1, and STARTRK-2).
- Treatment-related adverse events (AE) were seen in 93% of patients. Of these AE, 4% were grade 4, 31% were grade 3, and 59% were grade 1 or 2.
- Dose reductions were necessary in 34% of patients, discontinuation in 5%.
- Efficacy data are from 53 patients, of whom 23 had CNS metastases.
- ORR: 77.4%; median duration of response 24.6 months, median PFS 19 months, (median OS has not been reached).
- Duration of response and PFS were roughly twice as long for patients without CNS disease at baseline, but intracranial ORR was 55% with 20% CR.
Ignyta, Inc., a wholly owned subsidiary of F. Hoffmann-La Roche Ltd.