Neoadjuvant adebrelimab combined with chemotherapy in locally advanced esophageal squamous cell carcinoma: A single-arm, phase II trial.

Abstract

4090 Background: Neoadjuvant therapy is the standard treatment for patients with locally advanced resectable esophageal squamous cell carcinoma (ESCC). This study evaluated the efficacy and safety of adebrelimab (anti-PD-L1 antibody) combined with neoadjuvant chemotherapy and explored immune correlates associated with treatment response (ChiCTR2400085858). Methods: Patients with locally advanced ESCC (cT1b-T2N+M0 or cT3-4NanyM0) received three preoperative cycles of adebrelimab (1200 mg, IV, d1, Q3W) plus nab-paclitaxel (125 mg/m 2 , IV, d1, d8, Q3W) and carboplatin (AUC 5 mg/mL/min, IV, d1, Q3W). The primary endpoint was pathological complete response (pCR). Secondary endpoints included major pathological response (MPR), R0 resection rate, disease-free survival (DFS), overall survival (OS) and safety. PD-L1 expression was measured by immunohistochemistry using the combined positive score (CPS). Multiplex immunohistochemistry was performed to assess spatial immune microenvironment changes. Results: Forty-three patients were enrolled from October 2023 to June 2025. The median age was 61 years (range, 42-75), and 39 patients (91.0%) were male. Patients with cStage II/III/IVA were 6/16/22. Among the 35 patients who underwent surgery, all achieved R0 resection (100%), with pCR and MPR rates of 22.9% (8/35) and 45.7% (16/35), respectively. The median follow-up was 13.2 months (range 2.4-21.9), with 1-year DFS and OS estimates of 94.2% (95%Cl: 86.7%-100.0%) and 86.8% (95%Cl: 76.5%-98.4%). Patients with PD-L1 CPS ≥ 10 (57%, 20/35) demonstrated a higher pCR rate compared with those with PD-L1 CPS < 10 (43%, 15/35), specifically 30% (6/20) vs 13.3% (2/15). Multiplex immunohistochemistry revealed distinct spatial immune remodeling during neoadjuvant therapy. At baseline, PD-L1 expression was predominantly associated with CD11b⁺ myeloid cells in peritumoral regions and was enriched in good responders (TRG 0-1), accompanied by higher peritumoral CD3⁺ T-cell infiltration. Post-treatment analyses demonstrated divergent T-cell dynamics, with decreased peritumoral T-cell density in good responders (TRG 0-1) and increased infiltration in poor responders (TRG 2-3). Treatment-related adverse events were consistent with the known safety profile. The most common treatment-related grade 3/4 AEs were leukopenia (41.9%), alopecia (27.9%), thrombocytopenia (9.3%), anemia (7.0%), and hepatic dysfunction (2.3%). Conclusions: Neoadjuvant adebrelimab combined with chemotherapy demonstrated promising efficacy and manageable toxicity in patients with locally advanced ESCC. Myeloid-associated PD-L1 expression and treatment-induced T-cell redistribution may represent immune correlates of response and warrant further investigation. Clinical trial information: ChiCTR2400085858.