WCLC 2025 - Posters & ePosters-P3.18.55 A Phase II Study of Repotrectinib in ROS1-Positive Non-Small Cell Lung Cancer Patients With Active Brain Metastasis

P3.18.55 A Phase II Study of Repotrectinib in ROS1-Positive Non-Small Cell Lung Cancer Patients With Active Brain Metastasis - REPOSE

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The REPOSE trial (NCT06315010) is an international, multicenter, open-label, single-arm phase II study evaluating repotrectinib, a next-generation ROS1 tyrosine kinase inhibitor (TKI), in patients with metastatic non-small cell lung cancer (mNSCLC) harboring ROS1 rearrangements and active brain metastases (BMs). ROS1 rearrangements occur in 0.9–2.6% of mNSCLC cases, and brain metastases are common, affecting up to 50% of patients, with limited effective intracranial (IC) treatment options, especially post-resistance.<br /><br />The study includes adult (≥18 years) patients with histologically confirmed mNSCLC, measurable brain metastases per RANO-BM criteria, no prior ROS1 TKI treatment, and Eastern Cooperative Oncology Group performance status ≤2. Patients with leptomeningeal disease and those previously treated with chemotherapy or immunotherapy are eligible. The trial is recruiting at 18 sites across Spain, Austria, and Germany.<br /><br />Treatment involves repotrectinib administered orally at 160 mg daily for 14 days, then 160 mg twice daily until disease progression or withdrawal. The single-arm study follows Simon’s two-stage design with 20 total patients planned. The primary endpoint is intracranial objective response rate (IC-ORR) assessed by RANO-BM criteria; secondary outcomes include extracranial ORR, clinical benefit rate, progression-free and overall survival, safety, quality of life, and neurologic function.<br /><br />The study aims to demonstrate clinically meaningful IC activity, hypothesizing an IC-ORR of at least 35% to be considered positive. Interim analysis after 10 patients determines continuation based on responses. Repotrectinib previously exhibited promising intracranial efficacy in the TRIDENT-1 trial. REPOSE will provide targeted data on repotrectinib’s efficacy and safety in ROS1-positive mNSCLC patients with active brain metastases, addressing a significant unmet need for intracranial disease control. Funding is provided by Bristol-Myers Squibb.

Asset Subtitle

Thorsten Fuereder

Meta Tag

Speaker Thorsten Fuereder

Topic Clinical Trials in Progress

Keywords

REPOSE trial

repotrectinib

ROS1 tyrosine kinase inhibitor

metastatic non-small cell lung cancer

brain metastases

intracranial objective response rate

phase II study

Simon’s two-stage design

RANO-BM criteria

Bristol-Myers Squibb