Repotrectinib is being studied in an ongoing first-in-human dose-escalation phase 1/2 trial in patients with advanced cancers with ALK-, ROS1-, or NTRK1–3-gene fusion . Thus far, 65 patients have been enrolled and have received ≥1 dose of repotrectinib in 1 of 5 dose schedules (40–240 mg once a day or 160 mg twice a day). NSCLC is the most common tumour type among the enrolled patients. In addition, 35% of patients had baseline CNS metastatic disease, of which 52% was untreated.
In this trial, most adverse events were grade 1/2 . Dose-limiting toxicities were observed in two patients with NSCLC and the maximum tolerated dose has not been reached. Eight partial responses were observed; patients with responses included those who were tyrosine kinase inhibitor-naïve and who had pretreated disease, as well as in patients with solvent-front substitutions and wild-type fusions.
- Drilon A, Ou SI, Cho BC et al. Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations. Cancer Discov 2018; 8: 1227-1236.