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Repotrectinib: First Approval
1Springer Nature, Private Bag 65901, Mairangi Bay, Auckland, 0754, New Zealand. dru@adis.com.
Abstract:
Repotrectinib (AUGTYRO™) is a next-generation, oral, small-molecule kinase inhibitor of proto-oncogene tyrosine-protein kinase ROS1 (ROS1) and tropomyosin receptor tyrosine kinases (TRKs) TRKA, TRKB, and TRKC. It is being developed by Turning Point Therapeutics, a wholly owned subsidiary of Bristol-Myers Squibb (BMS), for the treatment of locally advanced or metastatic solid tumours, including non-small cell lung cancer (NSCLC). Repotrectinib is a next-generation tyrosine kinase inhibitor rationally designed to inhibit ROS1 and TRK fusion, including in the presence of resistance mutations such as solvent-front mutations. In November 2023, repotrectinib received its first approval in the USA for the treatment of adults with locally advanced or metastatic ROS1-positive NSCLC. Repotrectinib is under regulatory review in China and the EU for NSCLC. Clinical studies of repotrectinib are ongoing in several countries in patients with NSCLC and other solid tumours (including primary central nervous system cancer) across both adult and paediatric patient populations. In addition, preclinical investigation of repotrectinib in multiple myeloma is underway in the USA. This article summarizes the milestones in the development of repotrectinib leading to this first approval for the treatment of locally advanced or metastatic ROS1-positive NSCLC.
Insights
Repotrectinib (AUGTYRO™) is a new kinase inhibitor approved for ROS1-positive non-small cell lung cancer. It targets ROS1 and TRK fusions, including resistance mutations, offering a novel treatment option.
Area of Science:
- Oncology
- Pharmacology
- Drug Development
Background:
- Repotrectinib is a next-generation tyrosine kinase inhibitor targeting ROS1 and tropomyosin receptor tyrosine kinases (TRKs).
- It is developed for solid tumors, including non-small cell lung cancer (NSCLC), and designed to overcome resistance mutations.
- Bristol-Myers Squibb (BMS) subsidiary Turning Point Therapeutics is developing repotrectinib.
Purpose of the Study:
- To summarize the development milestones of repotrectinib.
- To highlight the first US approval for locally advanced or metastatic ROS1-positive NSCLC.
- To provide an overview of ongoing clinical studies and preclinical investigations.
Main Methods:
- Review of development history and regulatory submissions for repotrectinib.
- Analysis of preclinical and clinical data supporting efficacy and safety.
- Summary of ongoing studies in NSCLC, other solid tumors, and multiple myeloma.
Main Results:
- Repotrectinib received US approval in November 2023 for ROS1-positive NSCLC.
- The drug is under regulatory review in China and the EU for NSCLC.
- Clinical trials are ongoing in adult and pediatric populations for various cancers.
Conclusions:
- Repotrectinib represents a significant advancement in targeted therapy for ROS1-positive NSCLC.
- The drug's ability to inhibit ROS1 and TRK fusions, including resistance mutations, offers therapeutic potential.
- Ongoing research will further define its role in treating NSCLC and other malignancies.
