FDA Approves Augtyro for Patients With NSCLC Subset

The Food and Drug Administration (FDA) has approved Augtyro (repotrectinib) for patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

The drug, manufactured by Bristol Myers Squibb, is a type of tyrosine kinase inhibitor (TKI) that targets ROS1 oncogenic fusions. Augtyro’s approval arrived after the FDA accepted the New Drug Application in May 2023.

Augtyro was approved based on the phase 1/2 TRIDENT-1 trial, which analyzed the respective drug in TKI-naïve and TKI-pretreated patients with locally advanced or metastatic ROS1-positive NSCLC.

The trial included 71 patients and the primary endpoint (the main result measured at the end of a study to see if treatment worked) was overall response rate (ORR; percentage of patients who had a partial or complete response to treatment). Researchers of the trial established that the ORR was 79%, and 6% of patients experienced complete responses.

The median duration of response (DOR; length of time a tumor responds to treatment without the cancer growing or spreading) was 34.1 months, according to the news release. The ORR was 38% for 56 patients in the trial who were pretreated with one prior ROS1 TKI and did not previously receive chemotherapy, and the median DOR was 14.8 months.

“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” said Dr. Jessica J. Lin in a news release.“Based on the data we have seen in the TRIDENT-1 trial, (Augtyro) has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer.”

Lin is the TRIDENT-1 primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and assistant professor of medicine at Harvard Medical School.

The use of Augtyro is designed for minimal interactions which can lead to treatment resistance in patients with ROS1-positive metastatic NSCLC. The drug is expected to be available to patients within the U.S. around mid-December 2023.

“While progress has been made in the treatment of NSCLC over the past decade, there is still a need to address this particularly difficult-to-treat form of the disease with innovative science and a targeted approach,” said Dr. Samit Hirawat, executive vice president, chief medical officer, global drug development, Bristol Myers Squibb.“As the only approved next-generation TKI for ROS1-positive NSCLC patients, Augtyro builds on our legacy of delivering transformational therapies for patients with thoracic cancers.”

In terms of safety, 8% of patients permanently stopped receiving Augtyro, 48% had an interrupted dose of Augtyro because of side effects and 35% had dose reductions because of side effects. Serious side effects in at least 2% of patients included pneumonia, shortness of breath, pleural effusion (fluid buildup in the layers of tissue that line the lungs and chest cavity) and hypoxia (insufficient amount of oxygen in tissues).

“ROS1-positive NSCLC patients and their families face a stressful journey because our cancer can be difficult to treat, especially when it spreads to the brain,” said Janet Freeman-Daily, co-founder and president of The ROS1ders, a patient advocacy organization.“Today’s approval brings a new treatment option for the ROS1-positive patient community, which gives us hope for more time with loved ones.”

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