Simplified Perioperative Serplulimab and Chemotherapy for Resectable Squamous NSCLC: a Phase II Trial with Biomarker Analysis

PurposeSquamous non-small cell lung cancer (sq-NSCLC) is a distinct subtype of NSCLC. This exploratory, phase II study investigated the feasibility and efficacy of a four-cycle perioperative regimen combining serplulimab with a taxane (paclitaxel or nab-paclitaxel) and carboplatin in patients with resectable stage II-IIIA sq-NSCLC. MethodsThis investigator-initiated, single-arm, phase II exploratory trial (NCT05775796) enrolled patients with histologically confirmed, resectable clinical stage II-IIIA squamous NSCLC. Patients received 2-3 cycles of neoadjuvant serplulimab plus taxane-carboplatin, followed by curative-intent surgery and 1-2 cycles of adjuvant treatment. The primary endpoint was major pathological response (MPR). Secondary endpoints included pathological complete response (pCR), R0 resection rate, overall response rate (ORR), safety, event-free survival (EFS), and overall survival (OS). ResultsA total of 30 patients without actionable driver mutations were enrolled and 29 underwent surgery. The median age was 65 years, and most were male smokers (n=28, 93.33%). An R0 resection was achieved in 28 patients (93.33%), and the MPR and pCR rates were 76.67% and 50.00%, respectively. Based on radiological assessments during the neoadjuvant phase, the ORR was 73.33% (95% CI: 54.11-87.72). Grade 3 and more treatment-related adverse events were predominantly hematologic and were generally manageable. Long-term EFS and OS data are not yet mature. Additionally, exploratory minimal residual disease analysis using circulating tumor DNA (ctDNA) in 27 patients showed a strong correlation between ctDNA clearance and pCR (p=0.004), suggesting ctDNA as a promising biomarker for immunochemotherapy response. ConclusionsA four-cycle perioperative regimen of serplulimab combined with taxane-carboplatin demonstrated promising MPR and pCR rates with an acceptable safety profile in resectable sq-NSCLC patients. Long-term follow-up and future phase III trials are warranted to confirm survival benefits.