Repotrectinib (for both ROS1 TKI-naïve and ROS1 TKI-treated patients)

The phase I/II, single-arm TRIDENT-1 trial (NCT03093116) evaluated the safety and efficacy of repotrectinib in patients with advanced solid tumors with ALK, ROS1, NTRK1, NTRK2, or NTRK3 rearrangements. In total, 352 patients with ROS1 fusion–positive NSCLC were assigned to one of four cohorts based on previous exposure to a ROS1 TKI (yes vs. no) and/or to chemotherapy or immunotherapy (yes vs. no). The primary efficacy end point was objective response rate in two cohorts (n = 127): patients who had not previously received either a ROS1 TKI or chemotherapy/immunotherapy and patients who had previously received one ROS1 TKI but had not received chemotherapy/immunotherapy. Secondary end points included PFS, DOR, OS, and intracranial response.[78]

The phase I/II, single-arm TRIDENT-1 trial (NCT03093116) evaluated the safety and efficacy of repotrectinib in patients with advanced solid tumors with ALK, ROS1, NTRK1, NTRK2, or NTRK3 rearrangements. In total, 352 patients with ROS1 fusion–positive NSCLC were assigned to one of four cohorts based on previous exposure to a ROS1 TKI (yes vs. no) and/or to chemotherapy or immunotherapy (yes vs. no). The primary efficacy end point was objective response rate in two cohorts (n = 127): patients who had not previously received either a ROS1 TKI or chemotherapy/immunotherapy and patients who had previously received one ROS1 TKI but had not received chemotherapy/immunotherapy. Secondary end points included PFS, DOR, OS, and intracranial response.[78]

Among ROS1 TKI-naïve patients (n = 71), the objective response rate was 79% (95% CI, 68%–88%). Among patients who had received one prior ROS1 TKI and never received chemotherapy/immunotherapy (n = 56), the objective response rate was 38% (95% CI, 25%–52%). Responses were seen in six of eight pretreated patients with detectable TKI-resistance variants.[78][Level of evidence C3]

The phase I/II, single-arm TRIDENT-1 trial (NCT03093116) evaluated the safety and efficacy of repotrectinib in patients with advanced solid tumors with ALK, ROS1, NTRK1, NTRK2, or NTRK3 rearrangements. In total, 352 patients with ROS1 fusion–positive NSCLC were assigned to one of four cohorts based on previous exposure to a ROS1 TKI (yes vs. no) and/or to chemotherapy or immunotherapy (yes vs. no). The primary efficacy end point was objective response rate in two cohorts (n = 127): patients who had not previously received either a ROS1 TKI or chemotherapy/immunotherapy and patients who had previously received one ROS1 TKI but had not received chemotherapy/immunotherapy. Secondary end points included PFS, DOR, OS, and intracranial response.[78]

Among ROS1 TKI-naïve patients, the median PFS was 35.7 months (95% CI, 27.4–NE), and the median DOR was 34.1 months (95% CI, 26–NE). Among ROS1 TKI-treated patients, the median PFS was 9.0 months (95% CI, 6.8–19.6) and the median DOR was 14.8 months (95% CI, 7.6–NE). The median time to response was 1.8 months in both cohorts.

The phase I/II, single-arm TRIDENT-1 trial (NCT03093116) evaluated the safety and efficacy of repotrectinib in patients with advanced solid tumors with ALK, ROS1, NTRK1, NTRK2, or NTRK3 rearrangements. In total, 352 patients with ROS1 fusion–positive NSCLC were assigned to one of four cohorts based on previous exposure to a ROS1 TKI (yes vs. no) and/or to chemotherapy or immunotherapy (yes vs. no). The primary efficacy end point was objective response rate in two cohorts (n = 127): patients who had not previously received either a ROS1 TKI or chemotherapy/immunotherapy and patients who had previously received one ROS1 TKI but had not received chemotherapy/immunotherapy. Secondary end points included PFS, DOR, OS, and intracranial response.[78]

Among all patients with advanced solid tumors treated at the phase II recommended dose (n = 426), adverse events of grade 3 or higher occurred in 29% of patients. The most common grade 3 or higher adverse events were anemia (4%) and increased blood creatine kinase (4%). Adverse events led to dose reductions in 38% of patients, dose interruptions in 50% of patients, and treatment discontinuation in 7% of patients.