The Food and Drug Administration (FDA) has granted accelerated approval to repotrectinib (AUGTYRO, Bristol-Myers Squibb; BMS) for the treatment of adult and pediatric patients aged 12 and older with solid tumors harboring a neurotrophic tyrosine receptor kinase (NTRK) gene fusion. This approval covers patients with locally advanced or metastatic tumors for whom surgical resection would result in severe morbidity, as well as those whose disease has progressed following prior treatment or who lack satisfactory alternative therapies.
Image Source: Vinoth Khandelwal
Repotrectinib is an orally administered tyrosine kinase inhibitor (TKI) specifically designed to target TRK proteins resulting from NTRK gene fusions. This targeted approach aims to improve treatment efficacy while minimizing damage to healthy tissues. NTRK gene fusions are genetic alterations that result in the production of oncogenic TRK fusion proteins, driving the development and progression of various solid tumors. These fusions are rare but occur across a wide range of cancer types, making a targeted therapeutic approach essential for affected patients. Repotrectinib offers a new treatment option for this patient population, particularly those with limited alternatives.
Repotrectinib has received several expedited designations from the FDA, reflecting its potential to address significant unmet medical needs. These include priority review, fast track designation, breakthrough therapy designation, and orphan drug designation. These programs are part of the FDA’s efforts to accelerate the availability of treatments for serious conditions.
The efficacy of repotrectinib was evaluated in the TRIDENT-1 trial (NCT03093116), a multicenter, single-arm, open-label, multi-cohort study involving 88 adult patients with locally advanced or metastatic NTRK gene fusion-positive solid tumors. The confirmed ORR was 58% in TKI-naïve patients and 50% in TKI-pretreated patients. The median DOR was not estimable in the TKI-naïve cohort but was 9.9 months in the TKI-pretreated group. The most common adverse reactions (occurring in more than 20% of patients) included dizziness, dysgeusia, peripheral neuropathy, constipation, dyspnea, fatigue, ataxia, cognitive impairment, muscular weakness, and nausea.
The FDA’s accelerated approval of repotrectinib marks a significant advancement in the treatment of NTRK gene fusion-positive solid tumors, providing a new option for patients with limited alternatives. The robust response rates and manageable safety profile observed in clinical trials underscore the potential of repotrectinib to improve outcomes for this patient population. This approval highlights the importance of targeted therapies in oncology and the FDA’s commitment to expediting access to promising treatments for serious conditions.
Dr. Vinoth Khandelwal, Ph.D.
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