Abstract CT239: Neoadjuvant adebrelimab plus chemotherapy in untreated locally advanced head and neck squamous cell carcinoma: Efficacy and biomarker insights from a single-arm phase II trial

Abstract Background: Improving outcomes for locally advanced head and neck squamous cell carcinoma (LA-HNSCC) requires novel strategies. This phase 2 trial evaluated the efficacy and safety of neoadjuvant adebrelimab (a PD-L1 inhibitor) combined with chemotherapy in untreated, resectable LA-HNSCC. Methods: In this single-center, single-arm study (ChiCTR2400091171), eligible patients had newly diagnosed, resectable stage III-IVA/B LA-HNSCC. Patients received three cycles of neoadjuvant adebrelimab (1200 mg), nab-paclitaxel (260 mg/m²), and carboplatin (AUC 5) every 21 days. Subsequent local therapy (radical radiotherapy or surgery) was based on radiological response. The primary endpoint was objective response rate (ORR, RECIST v1.1). Secondary endpoints included safety, pathologic response, larynx preservation, and biomarker analysis. Results: Twenty-four patients were enrolled (median age 61.5 years; 91.7% male; 70.8% hypopharynx primary). Twenty-three completed all three cycles of neoadjuvant therapy and were evaluated for response by RECIST 1.1. The ORR was 87.5% (21/24) in the intention-to-treat population and 91.3% (21/23) in the per-protocol population, including 5 complete and 16 partial responses. The larynx preservation rate was 95.8%. Pathologic complete response was observed in 3 of 7 surgical patients (42.9%). Significant downstaging occurred in T-stage (66.7%), N-stage (70.8%), and overall stage (54.2%). All patients with p16-positive tumors (8/8) and those with PD-L1 combined positive score ≥20 (8/8) achieved an objective response. Grade 3 adverse events occurred in 41.7% of patients (primarily hematologic toxicities), with no grade 4/5 events. Conclusion: Neoadjuvant adebrelimab plus chemotherapy demonstrated high response rates, promising organ preservation, and manageable toxicity in resectable LA-HNSCC. Biomarker analysis suggests p16 positivity and high PD-L1 expression may correlate with better response. These findings support further investigation in randomized trials. Citation Format: Ruihua Fang, Bixue Huang, Lin Chen, Rongjian Zhan, Yicheng Deng, Weiping Wen, Wenbin Lei. Neoadjuvant adebrelimab plus chemotherapy in untreated locally advanced head and neck squamous cell carcinoma: Efficacy and biomarker insights from a single-arm phase II trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(8_Suppl):Abstract nr CT239.