Neoadjuvant serplulimab combined with cisplatin plus 5-fluorouracil in locally advanced head and neck squamous cell carcinoma: A phase II single-arm trial.

Abstract

e18063 Background: Head and neck squamous cell carcinoma (HNSCC) remains a formidable clinical challenge, characterized by aggressive behavior and dismal outcomes. While immunotherapy has reshaped the treatment landscape in recurrent or metastatic HNSCC, its role in the neoadjuvant setting for locally advanced disease remains to be defined. This study aimed to evaluate the efficacy and safety of serplulimab, a PD-1 inhibitor, in combination with the PF regimen (cisplatin + 5-fluorouracil) as neoadjuvant therapy for locally advanced HNSCC (LA-HNSCC). Here, we report a preliminary analysis of patients enrolled at the data cutoff in this ongoing study. Methods: This single-arm phase II trial enrolled patients with pathologically confirmed treatment-naïve LA-HNSCC. Participants received three cycles of neoadjuvant therapy comprising intravenous serplulimab (300 mg, q3w), cisplatin (25 mg/m²), and continuous intravenous infusion of 5-fluorouracil (1200 mg/m² over 96 hours). Subsequent definitive radiotherapy or surgical resection was selected based on post-treatment imaging assessment. The primary endpoint was objective response rate (ORR), and secondary endpoints include quality of life (QoL), survival, and safety. Results: As of the data cutoff, 17 patients had been enrolled, of whom 64.7% were male, and 47.05% had stage IV disease. Sixteen patients completed neoadjuvant therapy and were evaluable for response, among whom 7 achieved complete response, and 5 achieved partial response, yielding an ORR of 75.0% and a disease control rate (DCR) of 93.8%. QoL data were available for 16 patients who completed baseline and at least one follow-up assessment using the QLQ-C30 and QLQ-H&N35. Statistically significant improvements were observed in global health status, emotional functioning, and pain (QLQ-C30), as well as swallowing, speech, senses, and social eating (QLQ-H&N35) following neoadjuvant therapy; financial difficulties was the only domain that worsened. Treatment-related adverse events (TRAEs) were generally mild and manageable with appropriate interventions. At data cutoff, median follow-up was 19.0 months (range, 3.1-25.8). There were 5 overall survival (OS) events and 6 invasive disease-free survival (iDFS) events among the 17 patients, corresponding to 6-month OS and iDFS rates 100% and 94.1%, respectively. Longer-term survival outcomes are being assessed with ongoing follow-up. Conclusions: Neoadjuvant serplulimab combined with the PF chemotherapy demonstrated encouraging antitumor activity and a favorable safety profile in LA-HNSCC. The regimen was also associated with significant improvements across multiple patient-reported QoL domains. These findings support further investigation of this strategy as a potential neoadjuvant approach for LA-HNSCC. Clinical trial information: ChiCTR2500099204.