A phase II clinical study of neoadjuvant penpulimab combined with chemotherapy for patients with locoregionally advanced, resectable squamous cell carcinoma of the head and neck.

e18098 Background: Locally advanced squamous cell carcinoma of the head and neck (HNSCC) is associated with high risks of local recurrence and distant metastasis, resulting in poor prognosis. Neoadjuvant immunochemotherapy (NICT) has emerged as a promising strategy to improve outcomes. This study aimed to explore the safety and efficacy of penpulimab (PD-1 blockade) plus chemotherapy as neoadjuvant treatment for patients with HNSCC. Methods: This phase II trial enrolled patients with untreated, locoregionally advanced, resectable HNSCC (Stage III/IVa). Patients received three cycles of NICT consisting of penpulimab (200 mg), nab-paclitaxel (260 mg/m²), and cisplatin (75 mg/m²) on day 1 of each 21-day cycle, followed by surgery. The primary endpoint was the major pathological response rate (MPR). Postoperative patients achieving MPR were randomized 1:1 to receive either alternative adjuvant treatment (Penpulimab for low-to-intermediate recurrence risk, radiotherapy + Penpulimab for high recurrence risk) or standard treatment. Those not achieving MPR received standard treatment. Secondary endpoints included 2-year DFS, ORR, local & distant MFS, OS, pCR, and safety. Results: As of January 15, 2025, 63 patients who met the inclusion and exclusion criteria were enrolled, with a median age of 59 years, 79.4% male, 92.1% with an ECOG score of 0, 92.1% with oral cancer, and 46.0% and 54.0% in Stage III and IVa, respectively. A total of 59 patients completed neoadjuvant treatment, achieving an ORR of 86.4% and a DCR of 98.3%. Among them, 50 patients underwent surgery, all achieving R0 resection. Pathological evaluations revealed that 33 patients (66.0%) met the MPR criteria. In terms of safety, 88.9% of patients experienced all-grade treatment-related adverse events (TEAEs), with 27.0% reporting ≥Grade 3 TEAEs, mainly leukopenia (4.8%) and bone marrow suppression (4.8%). Immune-related adverse events (irAEs) occurred in 38.1% of patients, with 6.3% experiencing ≥Grade 3 irAEs. Conclusions: Neoadjuvant penpulimab combined with chemotherapy demonstrated high ORR and MPR rates, with an acceptable safety profile in resectable HNSCC. These results support further investigation of this regimen in larger, randomized trials. Clinical trial information: NCT06081673 .