FDA Grants Priority Review to Repotrectinib for the Treatment of NTRK-Positive Solid Tumors


Repotrectinib led to a durable anti-tumor response in patients with NTRK-positive locally advanced or metastatic solid tumors.

The FDA accepted a supplemental new drug application (sNDA) for repotrectinib (Augtyro), a next-generation tyrosine kinase inhibitor (TKI), for the treatment of patients aged 12 years and older with locally advanced or metastatic solid tumors with a neurotrophic tyrosine receptor kinase (NTRK) gene fusion; it will also be indicated for patients with a risk of severe morbidity following surgical resection, according to a Bristol Myers Squibb press release.

The FDA decision is based on results from the ongoing TRIDENT-1 and CARE trials, which demonstrate that repotrectinib leads to a durable anti-tumor response and is generally well-tolerated among patients.

3D Tumor Cancer Cells

Image credit: Nathan Devery com | stock.adobe.com

“While great advancements have been made over the last decade, patients with NTRK-positive locally advanced or metastatic solid tumors still experience significant unmet need,” said Joseph Fiore, PharmD, vice president and global repotrectinib program lead at Bristol Myers Squibb, in the press release. “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.”

TRIDENT-1 is an ongoing global multi-cohort phase 1/2 evaluating repotrectinib for safety, tolerability, pharmacokinetics, and anti-tumor activity in patients with advanced solid tumors, including patients with locally advanced or metastatic solid tumors and NTRK fusion. NTRK gene fusions are rare but significant because they propel cancer development. The phase 2 primary endpoint is overall response rate (ORR), and key secondary endpoints include duration of response (DOR), progression-free survival (PFS), and intracranial response across different cohorts.

CARE is a phase 1/2 open-label study evaluating repotrectinib for safety, tolerability, pharmacokinetics, and anti-tumor activity in pediatric and young adult patients with locally advanced or metastatic solid tumors and ALK, ROS1, or NTRK1-3 gene alterations. Phase 1 primary endpoints include dose-limiting toxicities and pediatric recommended phase 2 dose (RP2D). Secondary endpoints include ORR, clinical benefit rate (CBR), time to response (TTR), DOR, and intracranial ORR (IC-ORR). The phase 2 primary endpoint is ORR. Secondary endpoints are the same as the phase 1 trial, with the additions of PFS, central nervous system PFS (CNS-PFS) and overall survival (OS).

Repotrectinib was granted 4 Fast Track designations for a variety of cancer types, before receiving approval as treatment for locally advanced or metastatic ROS1-positive non-small cell lung cancer in November 2023. The FDA set a target action date of June 15, 2024, for the approval of repotrectinib as treatment for NTRK-positive tumors.

“We look forward to working closely with the FDA on the review of our application for repotrectinib for this tumor-agnostic indication and potentially offering patients with NTRK-positive disease a new, durable treatment option,” Fiore said in the press release.


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. BMS. News Release. February 14, 2024. Accessed on 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

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