Randomized, double-blind, phase 3 TRUST-IV study of adjuvant taletrectinib vs placebo in patients with stage IB–IIIA ROS1+ non-small cell lung cancer (NSCLC).

Abstract

TPS8130 Background: Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) approved by the US FDA for the treatment of locally advanced or metastatic ROS1+ NSCLC. In stage IB–IIIA NSCLC, which represents about 30% of NSCLC cases, the standard of care is surgical resection with perioperative systemic therapy (neoadjuvant or adjuvant). Results from Phase 3 trials have shown significantly improved outcomes for EGFR and ALK TKIs as adjuvant therapy compared with placebo or chemotherapy in early-stage NSCLC with EGFR mutations or ALK fusions, respectively. However, there remains an unmet need for patients with stage IB–IIIA ROS1+ NSCLC. Given the efficacy and tolerability of taletrectinib in advanced ROS1+ NSCLC, there is a rationale for investigating taletrectinib in patients with earlier-stage NSCLC who have undergone complete tumor resection. Methods: TRUST-IV (NCT07154706) is a randomized, double-blind, multicenter, Phase 3 study evaluating the efficacy and safety of taletrectinib compared with placebo in patients with stage IB, II, or IIIA ROS1+ NSCLC following curative surgery (negative surgical margins). ROS1 fusions may be detected using validated local tissue or liquid assays but must be confirmed by central tissue testing. Patients may have received prior adjuvant platinum-based chemotherapy (≤4 cycles) if clinically indicated, which must be completed ≥7 days prior to randomization. Surgical resection must have occurred 4–16 weeks prior to randomization if no adjuvant chemotherapy was given or 4–30 weeks if adjuvant chemotherapy was given. The estimated enrollment is 180 patients, randomized 2:1 to receive either taletrectinib 400 mg once daily or a matched placebo, stratified by prior adjuvant chemotherapy (yes vs no) and pathological stage (IB vs II vs IIIA). Patients will receive blinded study drug in continuous 28-day cycles until disease recurrence or consent withdrawal, or up to a maximum of 3 years. Contrast computed tomography or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis will be performed at screening, Cycle 4 Day 1 (C4D1), and C7D1, while brain MRI will be performed at screening and C7D1; thereafter, all imaging will be performed every 24 weeks until 5 years and then annually until disease recurrence or end of study. The primary endpoint is disease-free survival (DFS) by investigator assessment. Select secondary endpoints include: DFS rates at 2, 3, 4, and 5 years; DFS by blinded independent central review; overall survival; CNS-DFS; and safety. Exploratory endpoints include patient-reported outcomes for health-related quality-of-life measures and progression-free survival 2. The trial is currently recruiting. Clinical trial information: NCT07154706 .