Phase III study of multidisciplinary therapy combining local ablative therapy with immune-checkpoint inhibitors for patients with synchronous oligometastatic NSCLC (J-OLIGO: WJOG20924L).

Abstract

TPS8667 Background: The standard of care for stage IV non-small cell lung cancer (NSCLC) patients without actionable driver mutations is immune-checkpoint inhibitors (ICIs) with or without platinum-based chemotherapy. For patients with synchronous oligometastatic disease, local ablative therapy (LAT) to all lesions, including primary sites, may improve survival based on several randomized phase II trials. Furthermore, combining LAT with ICIs may enhance anti-tumor immune responses by reducing tumor burden. However, a recent large phase II/III study failed to demonstrate a survival benefit for adding LAT to systemic therapy in patients with synchronous or induced oligometastatic NSCLC. Consequently, it remains unclear whether LAT provides a survival benefit in synchronous oligometastatic NSCLC. Based on the promising results from our preceding phase II trial (TRAP-OLIGO; WJOG11118L), we initiated this phase III trial to definitively evaluate the benefit of adding LAT to pembrolizumab plus platinum-based chemotherapy specifically for synchronous oligometastatic NSCLC. Methods: J-OLIGO is a multicenter, open-label, randomized phase III intergroup trial. Eligible patients have untreated stage IV NSCLC, ECOG PS 0-1, 1–3 metastases, and no actionable driver mutations. During the induction phase, patients receive 4 cycles of pembrolizumab plus platinum-based chemotherapy. Patients who achieve disease control with induction therapy and remain eligible for LAT to all residual lesions are randomized (1:1) to either the LAT group (Intervention) or the standard group (Control). The feasibility and appropriateness of LAT for each patient are evaluated by a multidisciplinary tumor board, consisting of medical oncologists, radiation oncologists, and thoracic surgeons, to ensure definitive treatment of all viable lesions. The LAT group receives definitive surgery and/or definitive radiotherapy to all sites, followed by maintenance pembrolizumab (±pemetrexed). Stratification factors include number of metastases, PD-L1 TPS, histology, and induction response. The primary endpoint is overall survival (OS), defined as the time from randomization. Secondary endpoints include progression-free survival (PFS), objective response rate (ORR), and the safety. Based on results from previous studies, the study has 80% power to detect a hazard ratio of 0.55 for OS (median OS: 20 vs. 36 months) with a one-sided alpha of 0.05. The target sample size is 150 patients for primary registration and 100 for secondary registration. Accrual began in October 2025 and is planned for 4 years, followed by a 4-year follow-up period. This trial is supported by the Japan Agency for Medical Research and Development (AMED) under the Project for Innovative Cancer Research. Clinical trial information: jRCTs041250114.