FDA grants accelerated approval to Augtyro for NTRK-positive solid tumors
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The FDA granted accelerated approval to repotrectinib for the treatment of adults and children 12 years and older with solid tumors that have a neurotrophic tyrosine receptor kinase gene fusion.
The indication applies to individuals with locally advanced or metastatic disease who have progressed despite previous treatment and lack alternative therapeutic options. It also applies to those who are likely to experience severe morbidity if they underwent surgical resection.
Repotrectinib (Augtyro, Bristol Myers Squibb) — a tyrosine kinase inhibitor (TKI) — previously received fast track, breakthrough therapy and orphan drug designations by the FDA and expedited review.
FDA granted accelerated approval based on the results from the phase 1/phase 2 TRIDENT-1 trial, which assessed safety, tolerability, pharmacokinetics and antitumor activity of repotrectinib among adults and pediatric patients aged 12 years or older with locally advanced or metastatic solid tumors that harbor a neurotrophic tyrosine receptor kinase (NTRK) gene fusion.
The open-label, single-arm trial included 40 TKI-naive and 48 TKI-pretreated patients with 15 different cancer types. Among TKI-naive patients with a median follow-up of 17.8 months, researchers noted a confirmed objective response rate of 58% (95% CI, 41-73), with 43% experiencing partial responses and 15% complete responses.
Among TKI-pretreated patients with a median follow-up of 20.1 months, researchers reported a confirmed ORR of 50% (95% CI, 35-65), with all experiencing a partial response and no complete responses.
Based on clinical and pharmacokinetic data, researchers noted that the recommended dose of the agent for pediatric patients older than 12 is the same as adults — 160 mg orally once daily for 14 days, followed by 160 mg twice daily until either disease progression or unacceptable toxicity.
Dosage interruptions occurred in 50% of patients and dose reductions in 38% of patients because of adverse reactions.
Serious adverse events occurred in 35% of patients who received repotrectinib, including pneumonia (6.3%), dyspnea (3.1%), pleural effusion (2.8%) and hypoxia (2.6%).
Fatal adverse reactions occurred in 3.5% of patients, including pneumonia, pneumonia aspiration, cardiac arrest, sudden cardiac death, cardiac failure, hypoxia, dyspnea, respiratory failure, tremor and disseminated intravascular coagulation.
The most common adverse reactions included dizziness (65%), dysgeusia (54%), peripheral neuropathy (49%), constipation (38%), dyspnea (30%), fatigue (30%), ataxia (28%), cognitive impairment (25%), muscular weakness (20%) and nausea (20%).
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