Based on results from a trial of repotrectinib in patients with ROS1-positive locally advanced or metastatic non-small cell lung cancer, the FDA accepted the New Drug Application and set a Prescription Drug User Fee Act goal date of November 27, 2023.
Treatment with repotrectinib (Bristol Myers Squibb) demonstrated high response rates and durable responses, including robust intracranial responses, in patients with ROS1-positive locally advanced or metastatic non–small cell lung cancer (NSCLC) who were tyrosine kinase inhibitor (TKI)-naïve or previously treated with 1 TKI and no chemotherapy.
The new results from the TRIDENT-1 trial will be presented at the International Association for the Study of Lung Cancer 2023 World Conference on Lung Cancer in September. Alongside the updated results, median duration of response (DOR) and progression-free survival (PFS) will also be disclosed for the first time in the pooled phase 1/2 population.
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. Phase 1 includes several primary and secondary safety and pharmacokinetics endpoints, and phase 2 has a primary endpoint of overall response rate (ORR).
Based on results from the TRIDENT-1 trial, the FDA accepted the New Drug Application for repotrectinib for the treatment of patients with ROS1-positive locally advanced or metastatic NSCLC. It was also granted Priority Review and a Prescription Drug User Fee Act goal date was set for November 27, 2023.
“These updated results reflect the potential of repotrectinib as a best-in-class ROS1 inhibitor,” said Joseph Fiore, PharmD, executive director and global program lead on repotrectinib with Bristol Myers Squibb, in a press release. “Furthermore, the data offer hope for the patients with ROS1-positive non–small cell lung cancer who still face high remaining unmet needs.”
Repotrectinib is a next-generation, potential best-in-class TKI targeting ROS1- or NTRK-positive locally advanced or metastatic solid tumors, where there remain significant unmet medical needs for patients. It was designed to improve durability of response and with favorable properties to enhance intracranial activity and is being studied in a registrational phase 1/2 trial primarily in adults and a phase 1/2 trial in pediatric patients.
In the updated analysis, repotrectinib continued to demonstrate durable efficacy in this patient population. In TKI-naïve patients (n=71) with a median follow-up of 24 months, confirmed objective response rate (cORR) was 79%, and median DOR and PFS were 34.1 months and 35.7 months, respectively. Among the 9 patients with measurable brain metastases at baseline, intracranial ORR was 89% and responses were prolonged.
Among those who had been previously treated with 1 TKI and no chemotherapy (n=56) with median follow-up of 21.5 months, cORR was 38%, and median DOR and PFS were 14.8 months and 9 months, respectively. In this subset of patients with measurable brain metastases at baseline (n=13), intracranial ORR was 38%.
Finally, at the recommended dose for phase 2, the safety profile of repotrectinib was manageable and remained consistent with previous study data.
“The data from the TRIDENT-1 trial hold great significance in the field of non–small cell lung cancer research, as they add to the growing body of evidence pointing toward durable results with repotrectinib in patients who test positive for ROS1 gene fusions,” said Byoung Chul Cho, MD, PhD, from the Yonsei Cancer Center at the Yonsei University College of Medicine, in a press release. “With these results, we are seeing durable benefit, including in the brain, in patients with ROS1-positive NSCLC that differentiates repotrectinib from existing agents and is especially impressive in the context of historic data with current ROS1 TKIs. This targeted therapy has true potential to change the treatment landscape and become a new standard of care for patients with ROS1-positive NSCLC.”
The study is 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.
Updated data from TRIDENT-1 trial show durable efficacy benefits with repotrectinib for patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer. News release. Bristol Myers Squibb. August 16, 2023. Accessed August 17, 2023. https://news.bms.com/news/corporate-financial/2023/Updated-Data-from-TRIDENT-1-Trial-Show-Durable-Efficacy-Benefits-with-Repotrectinib-for-Patients-with-Locally-Advanced-or-Metastatic-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx