Bristol Myers Squibb's recent announcement of the accelerated approval of Augtyro™ (repotrectinib) by the U.S. Food and Drug Administration (FDA) marks a significant advancement in the treatment landscape for patients with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This approval extends to both adult and pediatric patients aged 12 and older who have locally advanced or metastatic disease and have either progressed following treatment or have no satisfactory alternative therapy.
The approval was based on findings from the Phase 1/2 TRIDENT-1 study, which demonstrated encouraging results in patients with NTRK-positive solid tumors. In both TKI-naïve and TKI-pretreated patients, Augtyro showed promising efficacy with a confirmed objective response rate (cORR) of 58% and 50%, respectively. Notably, a significant proportion of responding patients remained in response at one year, indicating durable benefit from Augtyro. Additionally, the drug exhibited intracranial activity in patients with measurable central nervous system (CNS) metastases.
Augtyro is associated with several warnings and precautions, including CNS effects, interstitial lung disease (ILD)/pneumonitis, hepatotoxicity, myalgia with creatine phosphokinase elevation, hyperuricemia, skeletal fractures, and embryo-fetal toxicity.
This approval represents a vital addition to the treatment armamentarium for patients with NTRK-positive tumors, addressing an unmet need in this patient population. The recommended dosage for Augtyro in pediatric patients aged 12 and older is consistent with that for adults.
Importantly, this is the second indication for Augtyro in the U.S., following its prior approval for the treatment of adult patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) in November 2023.
The TRIDENT-1 trial, which evaluated Augtyro, demonstrated its safety, tolerability, pharmacokinetics, and anti-tumor activity in patients with NTRK gene fusion-positive solid tumors. The safety profile of Augtyro was generally manageable, with the most common adverse reactions including dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.
NTRK gene fusions are rare alterations that lead to abnormal protein formation and may drive cancer growth. Testing for these fusions is crucial for identifying patients who may benefit from treatment with TRK inhibitors like Augtyro. The approval of Augtyro underscores the importance of precision medicine in oncology and offers hope to patients and their families facing these challenging diagnoses.
