OBJECTIVES: The safety and efficacy of repotrectinib, a tyrosine kinase inhibitor, is being evaluated in an ongoing phase 1/2 study (TRIDENT-1), in patients with advanced solid tumors harboring ROS1 or NTRK1-3 rearrangements. PROs were secondary endpoints to examine repotrectinib's impact on quality of life (GHS/QOL) and treatment-related symptoms as per EORTC Quality of Life core questionnaire (QLQ-C30) and lung cancer module (QLQ-LC13).

METHODS: Patients received 160 mg QD oral repotrectinib, with titration to 160 mg BID, if tolerated. PRO questionnaires were administered at screening, pre-dose day 1 of each cycle (month), and end-of-treatment visit. Change from baseline in GHS/QOL and treatment-related symptoms were summarized. Time to first improvement (TFI) and time to definitive deterioration (TDD) were assessed using Kaplan-Meier methods. Change in score >/= 10 points was prespecified as clinically-meaningful. Analysis was conducted using data from initiation through 11February 2022.

RESULTS: 156 patients with ROS1+ NSCLC (63 TKI-naive, 93 TKI-pretreated) were included for analysis. Mean changes over time remained stable or improved in the majority of scores; improvements were observed in GHS/QOL and key lung cancer (LC) symptoms (cough, pain in chest, and hemoptysis). Median TFI in GHS/QOL was 3.71 months for TKI-naive and 4.67 months for TKI-pretreated. Patients showed large improvements (> 20 points) in cough through cycle 16. Median TFI was rapid in LC symptoms (cough: TKI-naive 1.84 months, TKI-pretreated 2.89 months). TDD was extended in LC symptoms [cough: median 23.03 months, pre-treated; pain in chest: 23.98 months, TKI-naive]. 100% reported 'Not at All' for experiencing hemoptysis (cycle 6); dyspnea, 53% of TKI-naive demonstrated improved response (cycle 6) and delayed TDD (median 22.97 months).

CONCLUSIONS: Majority of patients reported stable or improved GHS/QOL and treatment-related symptoms. Interim PROs were consistent with top-line efficacy and safety data further supporting favorable benefit-risk profile of repotrectinib in advanced or metastatic ROS1+ NSCLC.