On May 30, 2023 Bristol Myers Squibb (NYSE: BMY) reported that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for repotrectinib, a next-generation tyrosine kinase inhibitor (TKI), for the treatment of patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer (NSCLC), based on results from the TRIDENT-1 trial (Press release, Bristol-Myers Squibb, MAY 30, 2023, View Source [SID1234632205]). The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of November 27, 2023.
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"Patients with ROS1-positive non-small cell lung cancer face a rare disease with a significant unmet medical need given the limited durability of benefit and emergence of resistance to approved therapies," said Jonathan Cheng, M.D., senior vice president and head of oncology development, Bristol Myers Squibb. "The FDA’s acceptance of this application marks an exciting milestone on our journey to bring this next-generation tyrosine kinase inhibitor to patients. If approved, this would represent a potential best-in-class option for TKI-naïve patients and a potential first-in-class option for patients with ROS1-positive NSCLC who have been previously treated with TKI, and for whom there are currently no approved targeted therapies available. We are eager to continue working closely with the FDA on the review of this precision medicine, which has shown unprecedented level of durability of responses and robust intracranial responses in patients with ROS1-positive NSCLC."
The filing was based on results from the registrational TRIDENT-1 study. In the trial, repotrectinib demonstrated high response rates and clinically meaningful durability of benefit in both TKI-naïve and TKI-pretreated patients, including those with ROS1 resistance mutations. The safety profile of repotrectinib was well characterized and manageable. Results from TRIDENT-1 were most recently presented at the 2022 EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) (ENA) Symposium. The study remains ongoing to assess long-term outcomes and additional endpoints across patient populations with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors. Bristol Myers Squibb thanks the patients and investigators involved with the TRIDENT-1 clinical trial.
Turning Point Therapeutics is a wholly owned subsidiary of the Bristol-Myers Squibb Company. As of August 2022, Bristol Myers Squibb acquired the leading clinical stage precision oncology company and its pipeline of investigational drugs across precision oncology and advanced solid tumors, including repotrectinib.
About TRIDENT-1
TRIDENT-1 is a Phase 1/2 open-label, global, multi-center, first-in-human clinical trial evaluating the safety, tolerability, pharmacokinetics and anti-tumor activity of repotrectinib (TPX-0005, BMS-986472) in patients with advanced solid tumors, including non-small cell lung cancer (NSCLC).Phase 1 of the trial includes several primary and secondary safety and pharmacokinetics endpoints. Phase 2 of the trial has a primary endpoint of overall response rate (ORR) as assessed by Blinded Independent Central Review (BICR) using RECIST v1.1 and key secondary endpoints including duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS) and clinical benefit rate (CBR) in six distinct expansion cohorts, including tyrosine kinase inhibitor (TKI)-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors.
About Lung Cancer
Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Survival rates vary depending on the stage and type of the cancer when diagnosed. ROS1 fusions are rare and occur in about 1-2% of patients with NSCLC. Patients with tumors that are ROS1-positive tend to be younger than the average patient with lung cancer, more often female and may have little to no smoking history. Per international treatment guidelines, ROS1 targeted agents are preferred in patients with a tumor harboring this alteration.