ESTRO 2025 - Abstract Book

S1311

Clinical - Lung

ESTRO 2025

945

Digital Poster Serplulimab-Based Induction and Sequential Chemoradiotherapy for Bulky Unresectable Stage III NSCLC: Study Design and Preliminary Results Chengxin Liu, Dan han, Xiaomeng Liu, Bingjie Fan, Hongfu Sun, Chengrui Fu, Wei Huang Department of Radiation Oncology, Shandong Cancer Hospital, Jinan, China Purpose/Objective: Concurrent chemoradiotherapy (cCRT) with immunotherapy consolidation is the standard treatment for unresectable stage III non-small cell lung cancer (NSCLC), but the 5-year survival rate remains below 50%. Induction immunochemotherapy before cCRT offers a promising new option, particularly for bulky, unresectable tumors that cannot be treated with radiotherapy. The efficacy of serplulimab-based immunochemotherapy has been confirmed for advanced NSCLC (ASTRUM-004 study). This study investigates the feasibility and antitumor activity of serplulimab combined with cCRT in bulky, unresectable stage III NSCLC. Material/Methods: This single-center, prospective, single-arm, phase II exploratory clinical trial uses a Simon two-stage design. Key inclusion criteria: (1) age 18-75; (2) ECOG score 0-1; (3) primary tumor ≥5 cm, tumor with pulmonary atelectasis, or with multi-station lymph node involvement; (4) unresectable stage III NSCLC; (5) no prior antitumor therapy; (6) negative driver genes mutations. Patients receive two cycles of serplulimab combined with pemetrexed or nab paclitaxel + cisplatin, followed by two cycles of cCRT, then serplulimab consolidation until disease progression, intolerable toxicities, or up to 12 months. Serplulimab was administered at 4.5 mg/kg every three weeks (Q3W). Primary endpoints include objective response rate (ORR) and lung V20 (volume receiving ≥20 Gy of radiation) before and after induction treatment. Secondary endpoints are disease control rate (DCR) and adverse events (AEs). Stage II proceeds if at least nine ORR events are observed in Stage I. Results: From July 2023 to June 2024, 15 patients were enrolled in Stage I. As of August 2024, the median follow-up was 3.8 months. All 15 patients completed immunochemotherapy induction and cCRT, with 14 patients continuing in study treatment. The median age was 67 years (range 52-75), most were male (93.3%), smokers (86.7%), and had squamous cell carcinoma (66.7%). The ORR was 80.0% (12/15; 95% CI, 51.9 - 95.7), with 2 patients achieving complete response, meeting the pre-specified endpoint. The DCR was 100.0% (15/15; 95% CI, 78.2 - 100.0). Lung V20 significantly decreased post-induction (34.0% ± 8.4% vs. 29.8% ± 7.8%, P = 0.003). The incidence of all-grade AEs was 80%, with 3 patients (20%) experiencing grade 3 immune-related AEs; no grade 4/5 AEs. Conclusion: Serplulimab combined with induction chemotherapy and sequential cCRT demonstrates clear antitumor activity and manageable safety in bulky, unresectable stage III NSCLC. Stage II enrollment is underway, with 9 patients currently enrolled.

Keywords: immunotherapy, chemoradiotherapy, stage III NSCLC

References: 1. Antonia SJ, Villegas A, Daniel D, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017 Nov 16;377(20):1919-1929. 2. Zhou C, Hu Y, Arkania E, et al. A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004). Cancer Cell. 2024 Feb 12;42(2):198-208.e3.