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FDA Approves Repotrectinib for Locally Advanced or Metastatic ROS1-Positive NSCLC


Repotrectinib achieved a high objective response rate and durable response in the pivotal TRIDENT-1 trial.

The FDA has approved repotrectinib (Augtryo) for the treatment of adult patients with locally advanced or metastatic ROS1-positive non–small cell lung cancer (NSCLC), Bristol Myers Squibb announced yesterday.1

3d rendered medically accurate illustration of lung cancer | SciePro - stock.adobe.com

3d rendered medically accurate illustration of lung cancer | SciePro - stock.adobe.com

Repotrectinib is an orally administered tyrosine kinase inhibitor (TKI) that targets ROS1 oncogenic fusions. The approval is supported by findings from the TRIDENT-1 study, a global, multi-center, single-arm, open-label, multi-cohort phase 1/2 clinical trial evaluating the safety, tolerability, pharmacokinetics, and anti-tumor activity of repotrectinib in patients with advanced solid tumors.

The primary end point of the study was objective response rate (ORR), or the proportion of patients treated within a certain time frame who experienced either a partial response (tumor size decreased) or complete response (no longer had signs of cancer). The study demonstrated an ORR of 79% (95% CI, 68-88). The median duration of response (mDOR) was 34.1 months.

Additionally, among patients who had been pretreated with 1 prior ROS1 TKI and no prior chemotherapy (n = 56), the ORR was 38% (95% CI, 25-52) and the mDOR was 14.8 months. Furthermore, among patients who had measurable central nervous system metastases at baseline, responses in intracranial lesions were seen in 7 of 8 TKI-naïve patients (n = 71), and in 5 of 12 patients who were pretreated with TKIs (n = 56).

“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, MD, TRIDENT-1 primary investigator, 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. "Based on the data we have seen in the TRIDENT-1 trial, repotrectinib has the potential to become a new standard of care option for patients with locally advanced or metastatic ROS1 fusion-positive lung cancer.”

The most common adverse reactions that occurred in at least 20% patients were dizziness (63%), dysgeusia (48%), peripheral neuropathy (47%), constipation (36%), dyspnea (30%), ataxia (28%), fatigue (24%), cognitive disorders (23%), and muscular weakness (21%).

Permanent discontinuation of repotrectinib occurred in 8% of patients in the study, with serious adverse events occurring in 33% of patients. Serious adverse events occurring in at least 2% of patients included pneumonia (5.7%), dyspnea (3.8%), pleural effusion (3.4%), and hypoxia (3%.) Furthermore, fatal adverse reactions occurred in 4.2% of patients, including death, pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardia failure, sudden death, hypoxia, dyspnea, respiratory failure, tremor, and disseminated intravascular coagulation.

Repotrectinib is associated with several warnings and precautions, including central nervous system effects, interstitial lung disease or pneumonitis, hepatoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.2

“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,” Samit Hirawat, MD, executive vice president and chief medical officer, Global Drug Development, Bristol Myers Squibb, said in a press release. “As the only approved next-generation TKI for ROS1-positive NSCLC patients, [repotrectinib] builds on our legacy of delivering transformational therapies for patients with thoracic cancers.”

Repotrectinib is expected to be available to patients in the United States beginning in mid-December 2023.


1. US food and drug administration approves Augtyro (repotrectinib), a next-generation tyrosine kinase inhibitor (TKI), for the treatment of locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC). News release. Bristol Myers Squibb. November 15, 2023. Accessed November 16, 2023. https://news.bms.com/news/details/2023/U.S.-Food-and-Drug-Administration-Approves-Augtyro-repotrectinib-a-Next-Generation-Tyrosine-Kinase-Inhibitor-TKI-for-the-Treatment-of-Locally-Advanced-or-Metastatic-ROS1-Positive-Non-Small-Cell-Lung-Cancer-NSCLC/default.aspx.

2. Augtyro. Prescribing information. Bristol Myers Squibb;2023. Accessed November 16, 2023. https://packageinserts.bms.com/pi/pi_augtyro.pdf

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