FDA Priority Review Granted to Augtyro for Solid Tumors Based on Phase I/II TRIDENT-1 Trial Data

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Bristol Myers Squibb’s supplemental New Drug Application (sNDA) for Augtyro (repotrectinib) has been granted Priority Review status by the FDA for patients aged 12 years and older with solid tumors that have neurotrophic tyrosine receptor kinase (NTRK) gene fusion, are locally advanced or metastatic, and for whom surgical resection will likely cause severe morbidity.¹ The sNDA for the next-generation tyrosine kinase inhibitor (TKI) was granted a Prescription Drug User Fee Act goal date of June 15, 2024.

“While great advancements have been made over the last decade, patients with NTRK-positive locally advanced or metastatic solid tumors still experience significant unmet needs. New and effective treatment options that may improve durability of response and address resistance to existing tyrosine kinase inhibitors are critical to helping patients with these aggressive tumors,” Joseph Fiore, vice president, global program lead, Augtyro, Bristol Myers Squibb, said in a press release. “We look forward to working closely with the FDA on the review of our application for Augtyro for this tumor-agnostic indication and potentially offering patients with NTRK-positive disease a new, durable treatment option.”¹

Augtyro is a potential best-in-class 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. Augtyro was approved in November 2023 to treat locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC).²

Further, it was granted orphan drug designation in 2017 and was previously granted 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.³

The FDA based its designation on findings from the Phase I/II TRIDENT-1 (NCT03093116) and the Phase I/II CARE (NCT04094610) trials. The findings from the CARE trial were used to support the TRIDENT-1 study. The CARE trial analyzed the safety and tolerability of Augtyro across different dose levels among pediatric and young adult patients with locally advanced or metastatic solid tumors that harbor ALK, ROS1 or NTRK1-3 gene alterations.

The ongoing, global, multicenter, single-arm, open-label, multi-cohort TRIDENT-1 trial analyzed the safety, tolerability, pharmacokinetics, and anti-tumor activity of the drug in patients with advanced solid tumors, including NSCLC. The trial included those with locally advanced or metastatic solid tumors that harbor ROS1 or NTRK fusions.

Across these trials, Augtyro showed clinically meaningful response rates in patients with NTRK-positive locally advanced or metastatic solid tumors. The durability of response with Augtyro was found to be robust across patient subsets, including among those with tumors that harbor common resistance mutations, with intracranial responses observed. In terms of safety, Augtyro was found to be well tolerated and generally manageable.

References

1. U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Augtyro™ (repotrectinib) for the Treatment of Patients with NTRK-Positive Locally Advanced or Metastatic Solid Tumors. Bristol Myers Squibb. News release. February 14, 2024. Accessed February 14, 2024. https://news.bms.com/news/corporate-financial/2024/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibbs-Application-for-Augtyro-repotrectinib-for-the-Treatment-of-Patients-with-NTRK-Positive-Locally-Advanced-or-Metastatic-Solid-Tumors/default.aspx

2. 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 February 14, 2024. 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

3. 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 February 14, 2024. 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