Repotrectinib Granted Breakthrough Therapy Designation By FDA for Solid Tumors With NTRK Gene Fusion


Patients with solid tumors and an NTRK gene fusion who experienced progressive disease appear to derive benefit from repotrectinib, which received a breakthrough therapy designation from the FDA.

The FDA has granted a breakthrough therapy designation to repotrectinib for the treatment of patients with solid tumors harboring an NTRK gene fusion who experienced progression after being treated with 1 to 2 previous TRK tyrosine kinase inhibitors (TKIs) plus or minus chemotherapy and who have no other treatment options, according to a press release from developer Turning Point Therapeutics.1

Next steps towards having repotrectinib potentially registered are expected to take place in a Type B meeting with the FDA during the first half of 2022. The indication marks the seventh regulatory designation for repotrectinib.

“We are excited to receive our second Breakthrough Therapy designation and seventh overall regulatory designation for repotrectinib,” Athena Countouriotis, MD, president and chief executive officer, at Turning Point Therapeutics, said in a press release. “There remains an unmet medical need for NTRK-positive, TKI-pretreated advanced solid tumor patients where there are no targeted therapies currently approved. We look forward to presenting additional clinical data from our TRIDENT-1 study of repotrectinib during the AACR-NCI-EORTC conference later this week, including a late-breaker plenary presentation where early clinical data from the NTRK EXP-5 and EXP-6 cohorts will be discussed.”

The agent was previously granted a breakthrough therapy designation for ROS1-positive metastatic non–small cell lung cancer (NSCLC) that has not been previously treated with a ROS1-targeting TKI. Additionally, repotrectinib has several other fast track designations for advanced ROS1-positive, ROS1 TKI–naïve NSCLC; advanced ROS1-positive NSCLC that has been previously treated with in a prior line with platinum-based chemotherapy and a ROS1 TKI; advanced ROS1-positive NSCLC patients pretreated with 1 prior ROS1 TKI and no previous platinum-based chemotherapy; and NTRK-positive patients with advanced solid tumors who have progressed following treatment with at least 1 prior line of chemotherapy and 1 to 2 prior TRK TKIs, as well as no other satisfactory treatments.

Repotrectinib was previously examined as part of the phase 1/2 TRIDENT-1 trial (NCT03093116), which examined the utility of the agent in ROS1-positive metastatic NSCLC.2 Early interim data from the phase 1 portion of the trial, which were presented at the World Conference on Lung Cancer, indicated that 11 patients experienced an overall response rate (ORR) of 91% (95% CI, 59%-100%) and 86% for the patients with ROS1-positive, TKI-naïve disease. Patients experienced a median duration of response of 23.1 months and investigators reported a median progression-free survival of 24.6 months (95% CI, 7.2–not reached). Additionally, the study included 2 cohorts of patients with NTRK gene fusions.


  1. Turning Point Therapeutics granted breakthrough therapy designation for repotrectinib treatment in patients with NTRK-positive, TKI-pretreated advanced solid tumors. News release. Turning Point Therapeutics. October 4, 2021. Accessed October 6, 2021.
  2. Cho BC, Doebele RC, Lin JJ, et al. Phase 1/2 TRIDENT-1 study of repotrectinib in patients with ROS1+ or NTRK+ advanced solid tumors. J Thoracic Oncol. 2021;16(3):MA11.07. doi:10.1016/j.jtho.2021.01.251
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