FDA Grants Breakthrough Therapy Designation to Repotrectinib for ROS1-Positive Metastatic NSCLC


Repotrectinib awarded breakthrough therapy designation for patients with ROS1-positive metastatic non–small cell lung cancer previously treated with a ROS1 tyrosine kinase inhibitor and who were not previously administered platinum-based chemotherapy.

The FDA has awarded breakthrough therapy designation (BTD) to repotrectinib (Turning Point Therapeutics Inc) for patients with ROS1-positive metastatic non–small cell lung cancer (NSCLC) who were previously treated with 1 ROS1tyrosine kinase inhibitor (TKI) and who were not previously administered platinum-based chemotherapy.1

Repotrectinib is a next-generation ROS1 and TRK TKI and was previously granted 2 BTDs. One of which was for patients with ROS1-positive metastatic NSCLC who have not received a ROS1 TKI. The other BTD was granted to repotrectinib for patients with advanced solid tumors that have an NTRK gene fusion and who progressed following treatment with 1 or 2 TRK TKIs, with or without prior chemotherapy, and who have no satisfactory alternative treatments.

“We are excited to receive our third breakthrough therapy designation and eighth overall FDA regulatory designation for repotrectinib in an indication where there are no approved targeted therapies,” said Mohammad Hirmand, MD, chief medical officer of Turning Point Therapeutics Inc, in a press release. “We are encouraged by the continued momentum in TRIDENT-1 with enrollment targets achieved in cohorts EXP-1, EXP-4 and EXP-6. We look forward to continuing to progress repotrectinib toward registration with our first pre-NDA meeting with the FDA to discuss the topline data by blinded independent central review from the ROS1-positive advanced NSCLC cohorts of the TRIDENT-1 study expected later this quarter.”

Repotrectinib was also previously granted 4 FDA Fast Track designations for ROS1-positive advanced NSCLC patients naïve to ROS1 TKI; ROS1-positive advanced NSCLC patients previously administered 1 line of platinum-based chemotherapy and 1 prior ROS1 TKI; ROS1-positive advanced NSCLC patients pretreated with 1 prior ROS1 TKI without previous platinum-based chemotherapy; and NTRK-positive patients with advanced solid tumors who progressed after treatment with at least 1 prior line of chemotherapy, 1 or 2 prior TRK TKIs, and who have no satisfactory alternative treatments. The drug was also granted an Orphan Drug designation in 2017.

The efficacy analyses supporting the latest BTD included approximately 50 patients from the phase 1 and 2 portions of the TRIDENT-1 (NCT03093116) study.

The trial includes 6 expansion cohorts, each of which is being analyzed for the primary end point of objective response rate (ORR). Secondary end points include duration of response (DOR), clinical benefit rate, progression-free survival, overall survival, and intracranial ORR.

Interim data from the expansion 4 cohort showed that among 5 patients with ROS1-positive NSCLC previously administered 1 TKI without chemotherapy, 4 patients had a complete response (CR) to repotrectinib.2 

The ORR in the cohort was 67% (95% CI, 22%-96%) and the DOR ranged from 1.0+ months to 5.7+ months. All patients who achieved a CR remained in response at the time of the data cutoff.

Enrollment across all 6 cohorts of TRIDENT-1 is open and continues progressing, according to Turning Point Therapeutics Inc.


  1. Turning Point Therapeutics granted breakthrough therapy designation for repotrectinib treatment in patients with one prior ROS1 tyrosine kinase inhibitor and no prior chemotherapy. News release. Turning Point Therapeutics. May 10, 2022. Accessed May 11, 2022. https://bit.ly/3wiwZVv
  2. Turning Point Therapeutics reports early interim data from registrational phase 2 trident-1 study of repotrectinib, provides regulatory update. News release. Turning Point Therapeutics. August 19, 2020. Accessed May 11, 2022. https://bit.ly/3iV1w3h
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