Simplified perioperative serplulimab and chemotherapy for resectable squamous NSCLC: a phase II trial with biomarker analysis

Purpose Squamous 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. Methods This investigator-initiated, single-arm, phase II exploratory trial ( NCT05775796 ) enrolled patients with histologically confirmed, resectable clinical stage II-IIIA squamous NSCLC. Patients received two to three cycles of neoadjuvant serplulimab plus taxane-carboplatin, followed by curative-intent surgery and one to two 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). Results A total of 30 patients without actionable driver alterations were enrolled and 29 underwent surgery. The median age was 65 years, and most were male smokers (n=28, 93.33%). Surgery was performed in 29 patients, and R0 resection was achieved in 96.55% (28/29) of the surgically resected patients. Among all enrolled patients, 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% to 87.72%). Grade ≥3 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. Conclusions A four-cycle perioperative regimen of serplulimab combined with taxane-carboplatin demonstrated promising MPR and pCR rates with an acceptable safety profile in patients with resectable sq-NSCLC. Long-term follow-up and future phase III trials are warranted to confirm these exploratory findings. Trial registration number NCT05775796 .