FDA Grants Priority Review to BMS for Treatment for Rare Form of NSCLC
May 31, 2023
Rare Daily Staff
The U.S. Food and Drug Administration granted priority review to Bristol Myers Squibb’s repotrectinib, a next-generation tyrosine kinase inhibitor for the treatment of patients with ROS1-positive locally advanced or metastatic non–small cell lung cancer.
The FDA is expected to act on the application by November 27, 2023.
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 percent 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 to 2 percent 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.
Repotrectinib is a potential best-in-class tyrosine kinase inhibitor (TKI) targeting ROS1- or NTRK-positive locally advanced or metastatic solid tumors, including non-small cell lung cancer (NSCLC), where there remain significant unmet medical needs for patients. Repotrectinib was designed to improve durability of response and with favorable properties for human brain penetration to enhance intracranial activity. It is being studied in a registrational phase 1/2 trial primarily in adults and a phase 1/2 trial in pediatric patients.
In June 2017, the U.S. Food and Drug Administration granted repotrectinib Orphan Drug designation. Since then, the FDA granted repotrectinib Breakthrough Therapy designations for the treatment of patients with: ROS1-positive metastatic NSCLC who have not been treated with a ROS1 TKI; ROS1-positive metastatic NSCLC who have been previously treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy; and advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with one or two prior tropomyosin receptor kinase (TRK) TKIs (with or without prior chemotherapy) and have no satisfactory alternative treatments.
Repotrectinib was also previously granted fast-track designations in patients with: ROS1-positive advanced NSCLC who have been treated with disease progression following one prior line of platinum-based chemotherapy and one prior line of a ROS1 TKI; ROS1-positive advanced NSCLC who have not been treated with a ROS1 TKI; ROS1-positive advanced NSCLC who have been previously treated with one ROS1 TKI and who have not received prior platinum-based chemotherapy; and advanced solid tumors that have an NTRK gene fusion who have progressed following treatment with at least one prior line of chemotherapy and one or two prior TRK TKIs and have no satisfactory alternative treatments.
“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, senior vice president and head of oncology development for Bristol Myers Squibb. “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.”
The filing was based on results from the registrational TRIDENT-1 study. In the trial, BMS said 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.
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.
Photo: Jonathan Cheng, senior vice president and head of oncology development for Bristol Myers Squibb
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