Efficacy and safety of perioperative sintilimab plus platinum-based chemotherapy for potentially resectable stage IIIB non-small cell lung cancer (periSCOPE): an open-label, single-arm, phase II trial.

Background: The absolute overall survival (OS) improvement with preoperative chemotherapy or chemoradiotherapy in locally advanced non-small cell lung cancer (NSCLC) patients is controversial and unsatisfactory. We designed this trial to explore the efficacy and safety of perioperative sintilimab plus platinum-based chemotherapy for potentially resectable stage IIIB NSCLC to facilitate further optimization of this therapeutic strategy. Methods: Patients diagnosed with stage IIIB NSCLC through invasive staging approaches and/or PET/CT scans and evaluated as having a high probability of radical resection of the primary lesion and metastatic lymph nodes with clear pathological margins by a multidisciplinary team were enrolled in this open-label, single-arm, phase II trial at a single centre in China. The participants received two cycles of intravenous neoadjuvant treatment with PD-1 inhibitor sintilimab (200 mg), pemetrexed (500 mg/m Findings: Forty-one patients were assessed for eligibility between December 2020 and August 2022; 30 patients were enrolled and given two cycles of neoadjuvant chemoimmunotherapy (neoCIT). Nineteen patients achieved a radiographic partial response, resulting in an ORR of 63.3%. Although 26 patients (86.7%) experienced TRAEs during the neoadjuvant phase, only two patients (6.7%) had ≥ grade 3 TRAEs. Surgical resection was performed on 27 patients (90%), with two patients experienced surgical delay because of coronavirus disease 2019, and the R0 rate was 96.4%. Twelve patients (44.4%) in the per-protocol (PP) population achieved an MPR, including six patients (22.2%) with a pCR. The most common postoperative complications were atrial fibrillation (6, 22.2%), pneumonitis (5, 18.5%), and heart failure (4, 14.8%); no deaths occurred within 90 days after surgery. As of October 31, 2024, the median follow-up was 34.7 months. The estimated EFS and OS rates at 36 months in the intention-to-treat population were 42.8% and 70.1%, respectively, and the estimated DFS and OS rates at 36 months in the PP population were 52.5% and 70.4%, respectively. Interpretation: Perioperative sintilimab plus platinum-based chemotherapy is an emerging treatment option for patients with potentially resectable stage IIIB NSCLC; it has a high response rate and tolerable treatment-related toxic effects, and enables radical resection in most patients. Funding: The Cancer Research Program of National Cancer Center (NCC201919B02), Shenzhen Clinical Research Center for Cancer (No. [2021]287), Shenzhen High-level Hospital Construction Fund, Shenzhen Key Medical Discipline Construction Fund (SZXK075) and Sanming Project of Medicine in Shenzhen (SZSM201612097) funded this study.