Dr Velcheti on the FDA Approval of Repotrectinib in ROS1+ Metastatic NSCLC

Vamsidhar Velcheti, MD, professor, Department of Medicine, New York University (NYU) Grossman School of Medicine, director, thoracic medical oncology, NYU Langone Perlmutter Cancer Center, discusses the significance of the FDA approval of the ROS1 TKI repotrectinib (Augtyro) in patients with ROS1-positive metastatic non–small cell lung cancer (NSCLC).

On November 15, 2023, the FDA approved repotrectinib for patients with locally advanced or metastatic NSCLC harboring ROS1 fusions. This regulatory decision was supported by findings from the phase 1/2 TRIDENT-1 trial (NCT03093116). In the phase 2 dose-expansion cohorts, patients with ROS1-positive locally advanced or metastatic NSCLC received repotrectinib at the recommended phase 2 dose (RP2D) of 160 mg daily for 14 days followed by 160 mg twice daily.

In the cohort of patients who were naive to TKIs, the agent elicited a confirmed overall response rate (cORR) of 79% (95% CI, 68%-88%) after a median follow-up of 24.0 months (range, 14.2-66.6). The median duration of response (DOR) was 34.1 months.

In the cohort of patients who had previously received 1 ROS1 TKI but no chemotherapy, administration of repotrectinib produced a cORR of 38% (95% CI, 25%-52%) after a median follow-up of 21.5 months (range, 14.2-58.6). The median DOR was 14.8 months (95% CI, 7.6-not estimable). In the TKI-pretreated cohort, 82% of patients had received prior crizotinib (Xalkori), and 16% of patients had received prior entrectinib (Rozlytrek).

The FDA approval of repotrectinib, a best-in-class ROS1 inhibitor, for patients with ROS1-positive metastatic NSCLC represents a significant development in the NSCLC treatment paradigm, Velcheti says. Two ROS1 inhibitors are already FDA approved for patients with NSCLC, Velcheti explains. Crizotinib was approved in 2016, and entrectinib was approved in 2019, both for patients with ROS1-positive metastatic NSCLC.

Repotrectinib is an important addition to the ROS1-positive metastatic NSCLC treatment paradigm because it is effective against gatekeeper resistance mutations that may occur after treatment with entrectinib or crizotinib, Velcheti concludes.