Protocol for a multicenter prospective phase II trial of adjuvant tislelizumab combined with S-1 in subjects with residual primary lesions and node-negative esophageal squamous cell carcinoma (PPIO-008)

The CheckMate 577 trial confirmed that adjuvant nivolumab improves survival in esophageal cancer patients with non-pathological complete response (non-pCR) following neoadjuvant chemoradiotherapy (NCRT). However, its generalizability to East Asian populations is constrained by three key limitations: only 29% of enrolled cases were esophageal squamous cell carcinoma (ESCC)–the predominant regional subtype; no significant survival benefit was observed in node-negative subgroups; and NCRT is increasingly supplanted by neoadjuvant immunochemotherapy (NICT) in clinical practice due to substantial postoperative morbidity and mortality. To address these critical evidence gaps, we initiated a multicenter, single-arm phase II trial investigating tislelizumab combined with S-1 as adjuvant therapy in ESCC patients with residual primary tumor but node-negative status (ypT1-4N0M0) after NICT. A total of 46 eligible patients will receive tislelizumab combined with S-1 for up to 1 year (17 cycles), unless disease recurrence, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion occurs. The primary endpoint is the 2-year disease-free survival (DFS) rate, with secondary endpoints including overall survival, incidence of treatment-related adverse events (TRAEs), and treatment tolerability. This study aims to establish a radiotherapy-sparing, personalized adjuvant strategy for high-risk East Asian ESCC patients post-NICT, addressing the unmet clinical need in this specific population.Clinical trial registration http://www.clinicaltrials.gov identifier is NCT06354140 (4 March 2024). Protocol version: V2.0, dated 15 October 2026.