TPS8659 Background: The advent of immune checkpoint inhibitors (ICIs) targeting the PD-1 pathway, including nivolumab, pembrolizumab, and atezolizumab, has significantly improved the efficacy outcomes, namely progression-free survival (PFS) and overall survival (OS), in the treatment of advanced non-small cell lung cancer (NSCLC). This improvement is underscored by the observation that some patients (pts) who responded to ICIs continued to show a response even after discontinuing the treatment. Consequently, cessation of ICIs may not adversely impact OS, while potentially reducing immune-related toxicity and financial burden. Methods: The JCOG1701 is a multi-institutional, two-armed, open-label, randomized phase III trial. The objective of this study is to confirm the non-inferiority of suspension of ICIs to their continuation in patients with advanced or recurrent NSCLC who have shown a positive response to ICIs for 12 months or longer. For patients in the suspension arm who experience disease progression, re-initiation of immune checkpoint inhibitors (ICIs) is conducted. The patients were randomized in a 1:1 ratio to either the continuation or discontinuation arms. Randomization was performed by the minimization method using the institution, histology (squamous vs. non-squamous), and drug/timing parameters (first-line pembrolizumab/atezolizumab vs. second-line atezolizumab vs. second-line nivolumab vs. second-line pembrolizumab vs. combined therapy with chemotherapy) as adjustment factors. The primary endpoint of the trial is OS, while secondary endpoints include PFS, time to treatment failure of strategy, response rate, PFS post resumption of ICIs, and safety. In the periodical blinded monitoring, the pooled Kaplan-Meier curve for OS seemed significantly better than planned. This motivated to change the primary analysis method from hazard ratio to a difference in 6-year restricted mean survival time with a non-inferiority margin of 5.6 months. With one-sided alpha of 5% and power of 70%, the study aimed to enroll 172 patients assuming that 2-year OS is 94% in both arms. As of Jan 2024, 162 patients have been randomized, with full enrollment projected by Nov 2024. The trial is registered in the Japan Registry for Clinical Trials as jRCT1031190032. An ancillary study exploring the predictive and prognostic role of circulating tumor DNA is also planned. The findings of the JCOG1701 will provide data for making more informed treatment decisions in advanced NSCLC, specifically related to the continuation or suspension of ICIs. Clinical trial information: CRB3180009 .