Repotrectinib Demonstrated Durable Clinical Activity Among Patients With ROS1 Fusion-Positive Non-Small Cell Lung Cancer

According to results from a phase 1/2 registrational study, repotrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), demonstrated durable clinical activity among patients with ROS1 fusion-positive non-small cell lung cancer (NSCLC), regardless of previous treatment with a ROS1 TKI. 

“The early-generation ROS1 [TKIs] that are approved for the treatment of ROS1 fusion–positive NSCLC have antitumor activity, but resistance develops in tumors, and intracranial activity is suboptimal,” stated Alexander Drilon, MD, Memorial Sloan Kettering Cancer Center, New York, New York, and coauthors. This study aimed to assess “the efficacy and safety of repotrectinib in patients with advanced solid tumors.” 

Based on phase 1 results, patients with advanced solid tumors including ROS1 fusion-positive NSCLC, treated with or without a ROS1 TKI received 160 mg of daily repotrectinib for 14 days followed by an additional 160 mg of twice daily repotrectinib. The primary efficacy end point was confirmed objective response. Secondary end points included duration of response (DOR), progression-free survival (PFS), and safety. 

Among patients previously not treated with a ROS1 TKI, response occurred in 79% of patients. The median DOR was 34.1 months and the median PFS was 35.7 months. Among patients previously treated with a ROS1 TKI, response occurred in 38% of patients. The median DOR was 14.8 months and the median PFS was 9 months. The most common treatment-related adverse events included dizziness (58%), dysgeusia (50%), and paresthesia (30%). Treatment discontinuation due to adverse events occurred in 3% of patients. 

As Dr Drilon and coauthors concluded, “Repotrectinib had durable clinical activity in patients with ROS1 fusion–positive NSCLC, regardless of whether they had previously received a ROS1 TKI [and] adverse events were mainly of low grade and compatible with long-term administration.” 

Source: 

Drilon A, Camidge DR, Lin JJ, et al. Repotrectinib in ROS1 fusion–positive non–small-cell lung cancer. N Engl J Med. Published online: January 11, 2024. doi: 10.1056/NEJMoa2302299