WCLC 2025 - Posters & ePosters-P3.18.62 TRUST-III: Phase 3 Head-To-Head Study of Taletrectinib vs Crizotinib in Patients With ROS1+ Non-Small Cell Lung Cancer

P3.18.62 TRUST-III: Phase 3 Head-To-Head Study of Taletrectinib vs Crizotinib in Patients With ROS1+ Non-Small Cell Lung Cancer

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The TRUST-III Phase 3 clinical trial (NCT06564324) evaluates taletrectinib versus crizotinib in patients with locally advanced or metastatic ROS1-positive non-small cell lung cancer (NSCLC) who have not previously received ROS1 tyrosine kinase inhibitors (TKIs). ROS1 gene fusions, present in approximately 2% of NSCLC cases, commonly occur in younger, female, never-smokers diagnosed at advanced stages. Crizotinib, the current standard of care, is limited by poor central nervous system (CNS) penetration and emerging resistance mutations (e.g., G2032R).<br /><br />Taletrectinib is a next-generation, oral ROS1 inhibitor designed to overcome these limitations, demonstrating CNS activity and efficacy against resistance mutations. Pooled analysis from earlier Phase 2 studies (TRUST-I and II) showed taletrectinib yields high confirmed objective response rates (88.8% in TKI-naïve patients) and durable responses (median progression-free survival [PFS] of 45.6 months), with a favorable safety profile. Common treatment-emergent adverse events included elevated liver enzymes, diarrhea, nausea, and vomiting, mostly mild to moderate in severity.<br /><br />The TRUST-III study is a randomized, open-label, multicenter trial enrolling approximately 138 patients in China. Participants receive either taletrectinib 600 mg once daily or crizotinib 250 mg twice daily in 28-day cycles. Key eligibility criteria include confirmed ROS1 NSCLC, measurable disease per RECIST v1.1 criteria, ECOG performance status 0–1, and stable CNS metastases allowed. The primary endpoint is PFS assessed by Blinded Independent Review Committee; secondary endpoints include objective response rate, duration of response, intracranial efficacy, overall survival, and safety.<br /><br />Taletrectinib received regulatory approval from China’s National Medical Products Administration in January 2025 and the US FDA in June 2025 for ROS1 NSCLC treatment. TRUST-III aims to confirm its clinical benefit versus crizotinib to support regulatory commitments in China. The study is ongoing, with estimated completion in 2030.

Asset Subtitle

Caicun Zhou

Meta Tag

Speaker Caicun Zhou

Topic Clinical Trials in Progress

Keywords

TRUST-III Phase 3 clinical trial

taletrectinib

crizotinib

ROS1-positive non-small cell lung cancer

NSCLC

ROS1 tyrosine kinase inhibitors

CNS metastases

progression-free survival

objective response rate

China National Medical Products Administration approval