8629 Background: Taletrectinib is a next-generation, CNS-active, selective ROS1 tyrosine kinase inhibitor (TKI) approved by the US FDA for the treatment of patients with locally advanced or metastatic ROS1+ NSCLC based on results from two Phase 2 studies, TRUST-I (NCT04395677) and TRUST-II (NCT04919811). Here we report PROs with taletrectinib from TRUST-II. Methods: Patients with locally advanced or metastatic ROS1+ NSCLC were treated with taletrectinib 600 mg once daily in 21-day cycles. HRQoL and PROs for cancer-specific symptoms were evaluated using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire 30-item core module (QLQ-C30) and 13-item lung cancer module (QLQ-LC13). Questionnaires were only distributed to patients from North America and Europe. Data were collected at screening, then subsequently on Day (D)1 of every cycle (C) until C9D1, on D1 of every three cycles until C27D1, and every four cycles thereafter until the end of treatment (within 7 days of last dose). Changes from baseline over time were summarized using descriptive statistics. A change in score of ≥10 points from baseline was considered clinically meaningful. Time to first improvement (TFI) was assessed using Kaplan–Meier methods. Results: At data cutoff (August 31, 2025), the analysis set included 69 patients (23 TKI-naïve and 46 TKI-pretreated). Mean changes from baseline improved or remained stable for most domains across both questionnaires. For global health status/quality of life, the majority of patients showed clinically meaningful improvement or remained stable at multiple timepoints assessed (e.g. 74% of patients at C7). Mean cognitive function score improved or remained stable throughout treatment, with the majority (63–77%) of patients showing improvement or stability and only 9–23% of patients showing worsening at various assessment times. Common disease-related symptoms, including pain and fatigue (QLQ-C30), and dyspnea and coughing (QLQ-LC13), showed consistent clinically meaningful improvement throughout treatment, with a median TFI of 1–3 months across all patients. Coughing was particularly improved in TKI-naïve patients, with a median TFI of < 1 month. Conclusions: Taletrectinib was associated with improved or stable HRQoL in the majority of patients and with rapid relief of disease-related symptoms. In contrast to other ROS1 TKIs, taletrectinib demonstrated preservation of cognitive function over time. Together with the efficacy and safety results, these data further support the use of taletrectinib for patients with ROS1+ NSCLC. Clinical trial information: NCT04919811 .
Elamin et al. (Thu,) studied this question.