FDA Gives Priority Review to Repotrectinib in Advanced ROS1+ NSCLC
Findings from the registrational phase 1/2 TRIDENT-1 trial support the new drug application for repotrectinib in the treatment of those with ROS1-positive advanced or metastatic non–small cell lung cancer.
The FDA has granted priority review to a new drug application (NDA) for the tyrosine kinase inhibitor (TKI) repotrectinib (TPX-0005, BMS-986472) in the treatment of patients with ROS1-positive locally advanced or metastatic non–small cell lung cancer (NSCLC), according to a press release from Bristol Myers Squibb.1
The FDA has set a Prescription Drug User Fee Act date of November 27, 2023 for repotrectinib in the treatment of patients with advanced ROS1-positive NSCLC.
The FDA has set a Prescription Drug User Fee Act date of November 27, 2023 for repotrectinib in this patient population.
Supporting data for the NDA came from the ongoing phase 1/2 TRIDENT-1 study (NCT03093116), in which repotrectinib yielded high response rates and clinically meaningful, enduring benefits in patients who received prior treatment with TKIs, including those with ROS1 mutations.
According to findings presented at the 2020 World Conference on Lung Cancer (WCLC) Singapore, repotrectinib demonstrated an overall response rate (ORR) of 91% (95% CI, 59%-100%) overall and 86% among those who were ROS1 TKI-naïve in a phase 1 cohort of 11 patients.2 Additionally, the median duration of response (DOR) was 23.1 months (95% CI, 5.6-not reached [NR]), and the median progression-free survival (PFS) was 24.6 months (95% CI, 7.2-NR).
“If approved, [repotrectinib] 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 TKIs, and for whom there are currently no approved targeted therapies available,” Jonathan Cheng, MD, senior vice president and head of Oncology Development at Bristol Myers Squibb, said in the press release. “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.”
Investigators of the open-label, global, multi-center, first-in-human phase 1/2 TRIDENT-1 trial are assessing the safety, tolerability, pharmacokinetics, and anti-tumor activity of repotrectinib among an estimated total of 500 patients with advanced solid tumors, including those with NSCLC. The trial’s 6 distinct expansion cohorts include TKI-naïve and TKI-pretreated patients with ROS1-positive locally advanced or metastatic NSCLC and NTRK-positive advanced solid tumors.
The primary end point in phase 2 of the trial is ORR per blinded independent central review assessment based on RECIST v1.1 criteria. Key secondary end points include DOR, time to response, PFS, overall survival, and clinical benefit rate.
Patients 12 years and older with histologically or cytologically confirmed locally advanced or metastatic solid tumors harboring an ALK, ROS1, NTRK1, NTRK2, or NTRK3 gene rearrangement were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 or 1, at least 1 measurable lesion per RECIST v1.1 criteria, and a life expectancy of at least 3 months. Patients who received prior immunotherapy or cytotoxic chemotherapy were also able to enroll.
Patients with symptomatic brain metastases or leptomeningeal involvement were unable to enroll on the trial. Patients were also unsuitable for enrollment if they had clinically significant cardiovascular disease, known active infections, or gastrointestinal disease or other malabsorption syndromes that would affect drug absorption.
References
- U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for repotrectinib for the treatment of patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer. News release. Bristol Myers Squibb. May 30, 2023. Accessed May 30, 2023. bit.ly/3oAEl6P
- 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. Presented at: International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer; January 28-31, 2021; Virtual. Abstract 3255.
