Neoadjuvant adebrelimab plus chemotherapy in untreated locally advanced head and neck squamous cell carcinoma: Efficacy and biomarker insights from a single-arm phase 2 trial.

6106 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, 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. 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. 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. Clinical trial information: ChiCTR2400091171 . Efficacy outcomes based on full analysis set (FAS). Efficacy Parameter Overall (N=24) Larynx (n=4) Hypopharynx (n=17) Oropharynx (n=3) Best Overall Response, n (%) CR 5 (20.8) 1 (25.0) 4 (23.5) 0 (0.0) PR 16 (66.7) 3 (75.0) 10 (58.8) 3 (100.0) SD 3 (12.5) 0 (0.0) 3 (17.6) 0 (0.0) PD 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) ORR 21 (87.5, ) 4 (100.0) 14 (82.4) 3 (100.0) (95% CI) (67.6 - 97.3) (39.8 - 100.0) (56.6 - 96.2) (29.2 - 100.0) (95% CI) (48.9 - 87.4) (19.4 - 99.4) (38.3 - 85.8) (29.2 - 100.0) Larynx Preservation Rate 23 (95.8) 4 (100.0) 16 (94.1) 3 (100.0) (95% CI) (78.9 - 99.9) (39.8 - 100.0) (71.3 - 99.9) (29.2 - 100.0) DCR 24 (100.0) 4 (100.0) 17 (100.0) 3 (100.0) (95% CI) (85.8 - 100.0) (39.8 - 100.0) (80.5 - 100.0) (29.2 - 100.0) Data are n (%, 95% CI). FAS: full analysis set (all enrolled patients receiving at least one treatment cycle); ORR: objective response rate (CR + PR); DCR: disease co