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The FDA's approval of Bristol Myers Squibb’s repotrectinib (Augtyro) was based on findings from the open-label, single-arm, Phase 1/2 trial TRIDENT-1, which evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of the drug in patients with advanced solid tumors.
The FDA has approved Bristol Myers Squibb’s repotrectinib (Augtyro) to treat locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).1 Repotrectinib is a next-generation, potential best-in-class tyrosine kinase inhibitor (TKI) that targets ROS1- or NTRK-positive locally advanced or metastatic solid tumors. The drug was designed to improve the durability of response and with favorable properties that improve intracranial activity.
“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, chief medical officer, Global Drug Development, Bristol Myers Squibb, said in a press release.1 “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.”
The regulatory action was based on findings from the open-label, single-arm, Phase 1/2 trial TRIDENT-1 study. TRIDENT-1 evaluated the safety, tolerability, pharmacokinetics, and anti-tumor activity of Augtyro in patients with advanced solid tumors.
Phase 1 of the trial evaluated safety and pharmacokinetic endpoints. Phase 2 evaluated the primary endpoint of overall response rate (ORR) and key secondary endpoints of duration of response (DOR), time to response, progression-free survival, overall survival, and clinical benefit rate in patients treated with or without a TKI and who have ROS1-positive locally advanced or metastatic NSCLC or NTRK-positive advanced solid tumors.2
Among TKI-naïve patients (n=71), ORR was 79% and the median DOR (mDOR) was 34.1 months. Among patients previously administered one ROS1 TKI with no prior chemotherapy, the ORR was 38% and the mDOR was 14.8 months. Among patients with measurable central nervous system metastases at baseline, 7 of 8 TKI-naïve patients (n=71) and 5 of 12 patients who were TKI-pretreated showed responses in intracranial lesions.
“New treatment options continue to be needed for patients with ROS1 fusion-positive NSCLC that support important clinical goals, including achieving durable therapeutic responses,” TRIDENT-1 primary investigator Jessica J. Lin, MD, 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.1 “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 FDA granted Augtyro with orphan drug designation in 2017 and previously awarded three breakthrough therapy designations for patients with metastatic disease with ROS1 or NTRK gene fusions and who are TKI-naive or TKI-pretreated, as well as four fast-track designations for patients with treated or untreated ROS1-positive advanced NSCLC or NTRK gene fusion.2
In August 2022, Bristol Myers Squibb acquired Turning Point Therapeutics and its pipeline of investigational drugs across precision oncology and advanced solid tumors, including Augtyro.
“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, in a press release.1 “Today’s approval brings a new treatment option for the ROS1-positive patient community, which gives us hope for more time with loved ones.”
1. 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). Bristol Myers Squibb. News release. Published November 15, 2023. Accessed November 16, 2023. https://news.bms.com/news/corporate-financial/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. Bristol Myers Squibb. U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Repotrectinib for the Treatment of Patients with Locally Advanced or Metastatic ROS1-Positive Non-Small Cell Lung Cancer. News Release. May 30, 2023. Accessed November 16, 2023. https://news.bms.com/news/details/2023/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Application-for-Repotrectinib-for-the-Treatment-of-Patients-with-Locally-Advanced-or-Metastatic-ROS1-Positive-Non-Small-Cell-Lung-Cancer/default.aspx