Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three...

Area of Science:

• Oncology
• Pharmacology
• Genetics

Background:

• Entrectinib targets tropomyosin receptor kinase (TRK) A, B, and C, showing anti-tumour effects in NTRK gene fusion-positive solid tumours.
• Its ability to cross the blood-brain barrier suggests potential efficacy in central nervous system (CNS) involvement.

Purpose of the Study:

• To analyze the efficacy and safety of entrectinib in patients with NTRK gene fusion-positive metastatic or locally advanced solid tumours.
• To evaluate objective response rates and duration of response in a TRK inhibitor-naive population.

Main Methods:

• Integrated analysis of three early-phase clinical trials (ALKA-372-001, STARTRK-1, STARTRK-2).
• Patients (≥18 years) with NTRK fusion-positive solid tumours received oral entrectinib (≥600 mg/day).
• Efficacy evaluated by blinded independent central review; safety assessed across multiple patient cohorts.

Main Results:

• Objective response observed in 57% (31/54) of efficacy-evaluable patients, including complete and partial responses.
• Median duration of response was 10 months.
• Most common Grade 3/4 treatment-related adverse events included increased weight and anemia; no treatment-related deaths occurred.

Conclusions:

• Entrectinib induces durable and clinically meaningful responses in patients with NTRK fusion-positive solid tumours.
• The drug exhibits a manageable safety profile, positioning it as a safe and active treatment option.
• Routine testing for NTRK fusions is recommended to expand therapeutic choices for eligible patients.