FDA Grants Approval to Repotrectinib for Locally Advanced or Metastatic Non-Small Cell Lung Cancer

December 6th 2023  /  12:15 PM PST


By: Dr. Anish Shah
Bronx-Lebanon Hospital; Bronx, NY


On November 15, 2023, the U.S. Food and Drug Administration approved Repotrectinib (Augtyro) for adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer.


Study ID: NCT03093116


Approval was based on the phase 1/2 TRIDENT-1 study, a global, multicenter, single-arm, open-label, multicohort trial that included 264 patients with locally advanced or metastatic NSCLC harboring ROS1 fusions. Repotrectinib was given at a dose of 160 mg once daily for 14 days and then increased to 160 mg twice daily until progressive disease or unacceptable toxicity was observed.


Efficacy was established on the primary endpoints of objective response rate (ORR) and duration of response (DOR) per blinded independent central review (BICR) assessment and by RECIST v1.1 criteria.


Patients who had not previously been treated with TKI demonstrated a confirmed ORR of 79% (95% CI, 68%-88%) when treated with Repotrectinib. This response rate included a full response in 6% of patients and a partial response in 73%. The median duration of response (DOR) in these patients was 34.1 months, with 70% of them showing a response that lasted a year or more. Conversely, in patients who had been treated with one prior ROS1 TKI but had not received prior chemotherapy or immunotherapy, the confirmed ORR was 38% (95% CI, 25%-52%), and the median DOR was 14.8 months. Notably, nearly half (48%) of these patients had a response that continued for at least a year. Furthermore, in patients with measurable intracranial lesions at the start of the study, 7 out of 8 TKI-naive patients and 5 out of 12 TKI- pretreated patients showed a response.


The most common adverse effects (AEs) reported in patients included dizziness, dysgeusia (taste distortion), peripheral neuropathy (nerve damage), ataxia (lack of muscle control), cognitive disorders, headache, constipation, nausea, diarrhea, vomiting, dyspnea (shortness of breath), cough, fatigue, edema (swelling), muscle weakness, myalgia (muscle pain), weight gain, and vision disorders. A small percentage of these cases were severe.


In conclusion, the study suggests that Repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion–positive lung cancer.


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