2282 - Serplulimab plus Chemoradiotherapy for Unresectable Locally Advanced Esophageal Squamous Cell Carcinoma: A Single-Arm, Multicenter, Phase I/II Trial (SCR-ESCC-02)
Presenter(s)
X. Y. Song1, W. Yu1, X. Fu1, X. Xu2, X. Ma2, and Y. Bai3; 1Department of Radiation Oncology, Shanghai Chest Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China, 2Department of Radiation Oncology, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China, 3Department of Radiation Oncology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Purpose/Objective(s): Definitive chemoradiotherapy (CRT)is the standard treatment for unresectable locally advanced esophageal squamous cell carcinoma (ESCC). Combining Serplulimab with induction chemotherapy and concurrent CRT may improve survival outcomes, potentially offering a new treatment strategy for locally advanced ESCC.
Materials/Methods: This study is a single-arm, Phase I/II trial for patients(pts) with unresectable locally advanced (ESCC), including a safety run-in (Phase I, n=15) followed by a Simon's two-stage expansion (Phase II, n=35). All pts received 2 cycles of induction Serplulimab (4.5 mg/kg, D1, Q3W) c, nab-paclitaxel (125 mg/m², D1,8, Q3W) and carboplatin (AUC=5, D1, Q3W). Three weeks post-induction, pts were stratified by predicted major pathological response (MPR) using a CT and biopsy-based model. MPR pts received reduced-dose radiotherapy (PTV-C 45 Gy/25Fx; PTV-G 50 Gy/25Fx); non-MPR pts received standard-dose radiotherapy (PTV-C 50 Gy/25Fx). During radiotherapy, all pts received concurrent Serplulimab (4.5 mg/kg, Q3W), weekly nab-paclitaxel (80 mg/m², QW), and carboplatin (AUC=2, QW) for up to 5 weeks, followed by Serplulimab maintenance until progression, unacceptable toxicity, or 1 year. The primary endpoint is progression-free survival (PFS), and secondary endpoints are overall survival (OS) and safety.
Results: As of December 2025, 39 pts were enrolled with median age of 68 years [IQR 60–70]. The majority were male (36/39, 92%), and most with T3–4 (33/39, 85%) and N0–1 (26/39, 67%). All pts completed induction therapy, MPR rate among pts completing induction was 49% (19/39). During induction therapy, the overall AEs incidence rate was 62% (24/39), the most common grade 3-4 AEs were myelosuppression (10%, 4/39). Prior to radiotherapy, 39 pts received concurrent immunotherapy with chemoradiotherapy (ICRT). Observed response per RECIST1.1 was 16 complete response (CR) and 17 partial response (PR), objective response rate (ORR) was 85% and disease control rate (DCR) was 97%. During ICRT, the overall AEs incidence rate was 100% (39/39), with grade 3-4 AEs incidence rate of 49% (19/39). The most common grade 3-4 AEs were myelosuppression (41%, 16/39),and radiation esophagitis (18%, 7/39). No AE was fatal. This study is still ongoing, and longer follow-up will provide more solid evidence.
Conclusion: This combination therapy showed manageable toxicity that could provide a new strategy for locally advanced ESCC.
Clinical trial information: NCT06173986