FDA Approves Augtyro to Treat ROS1 Positive Lung Cancer

The FDA has approved Bristol Myers Squibb’s Augtyro (repotrectinib) to treat adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).

Lung cancer is the leading cause of cancer deaths in the United States. ROS1 fusions are rare and occur in about 1% to 2% of patients with NSCLC. These cancers tend to be more aggressive and can spread to the brain.

Augtyro is an oral tyrosine kinase inhibitor (TKI) that targets ROS1 fusions. It is designed to minimize interactions that can lead to certain forms of treatment resistance in ROS1-positive metastatic NSCLC patients. Augtyro was developed by Turning Point Therapeutic, which Bristol Myers Squibb acquired in 2022.

Augtyro is expected to be available in mid-December 2023. The dosing for Augtyro is 160 mg orally once daily for 14 days, then increased to 160 mg twice daily until disease progression or unacceptable toxicity.

The monthly wholesale acquisition cost (WAC) for an adult is $29,000 based on 30-day costs at 160 mg BID. Patients with commercial insurance may be eligible for a $0 co-pay offer through the BMS Access Support Co-Pay Assistance Program, which has an annual maximum benefit of $15,000. Medicare Part D patients without the low income subsidy pay a total of about $3,333 a year using 2024 Medicare Part D benefit design thresholds.

A BMS spokesperson said the company is meeting with payers about coverage of Augtyro.

Several other therapies are available to treat ROS1 positive NSCLC, including Xalkori (crizotinib), Zykadia (ceritinib), Lorbrena (lorlatinib), and Rozlytrek (entrectinib).

Jessica J. Lin, M.D.

“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” Jessica J. Lin, M.D., primary investigator and attending physician at the Center for Thoracic Cancers at Massachusetts General Hospital and assistant professor of Medicine at Harvard Medical School, said in a press release.

The approval is based on the TRIDENT-1 study, which was an open-label, single-arm, phase 1/2 trial that evaluated Augtyro in 71 TKI-naïve and 56 TKI-pretreated patients. For TKI-naïve patients, the primary endpoint of objective response rate (ORR) was 79%. The median duration of response (mDOR) was 34.1 months.

Among patients pretreated with one prior ROS1 TKI and no prior chemotherapy, the objective response rate was 38% and the median duration of response was 14.8 months. Among patients who had measurable brain metastases, responses in intracranial lesions were seen in seven of eight TKI-naïve patients and five of 12 of those who were TKI-pretreated.

In the trial, 8% of patients discontinued treatment because of adverse events. Dosing was interrupted because of an adverse reaction in 48% of patients, and dose reductions because of an adverse event occurred in 35% of patients.

Serious adverse reactions occurred in 33% of patients who received Augtyro, including pneumonia, dyspnea, pleural effusion and hypoxia. Fatal adverse reactions occurred in 4.2% of patients who received Augtyro, including death, pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.

Updated data from the TRIDENT-1 study were presented at the World Lung Conference in September 2023. In this updated analysis, Augtyro continued to demonstrate durable efficacy in patients with ROS1-positive NSCLC, including intracranial activity. The study is ongoing to assess long-term outcomes and additional endpoints across patient populations.