越来越多的证据表明,放疗可能会增强免疫治疗的疗效。本研究旨在评估靶向PD-L1和CTLA-4的双特异性抗体KN046联合化疗和姑息性放疗治疗晚期食管鳞状细胞癌(ESCC)的可能性。在这个开放标签中,Ib期试验,晚期ESCC患者接受化疗和姑息性放疗,和KN046,预定义的递增剂量为1、3或5mg/kg(在化疗周期中每3周一次,在KN046维持期间每2周一次)。化疗方案包括顺铂(75mg/m2,d1)和紫杉醇(135-175mg/m2ivgtt。,d1).放射治疗细节,包括网站,定时,剂量,和碎片模式,由调查员自行决定。主要结果是剂量限制性毒性(DLT)。从2019年5月到2021年4月,在剂量组中招募了25名患者:1mg/kg中的3名,3mg/kg中的12,和10在5mg/kg。在剂量递增期间未观察到DLT。客观缓解率为41.7%(95CI22.1-63.4),而疾病控制率为87.5%(95CI67.6~97.3)。中位随访时间为11.8个月,中位无进展生存期为7.8个月(95CI5.2~9.7),中位总生存期为15.9个月(95CI8.4-NE).48.0%的患者报告了严重不良事件,主要是白细胞减少症(16%),免疫介导性小肠结肠炎(12%),免疫介导的肺炎(8%),和中性粒细胞减少(8%)。KN046联合化疗和姑息性放疗可能是可行的,在晚期ESCC患者中显示出良好的安全性和显着的疗效。
There is growing evidence to suggest that radiotherapy might enhance the efficacy of immunotherapy. This study aimed to assess the possibility of KN046, a bispecific antibody targeting PD-L1 and CTLA-4, combined with chemotherapy and palliative radiotherapy for advanced esophageal squamous cell carcinoma (ESCC). In this open-label, phase Ib trial, patients with advanced ESCC were administered chemotherapy with palliative radiotherapy, and KN046 in the predefined escalation dosages of 1, 3, or 5 mg/kg (every 3 weeks during chemotherapy cycles and every 2 weeks during KN046 maintenance). The chemotherapy regimen constituted cisplatin (75 mg/m2 i.v., d1) and paclitaxel (135-175 mg/m2 ivgtt., d1). Radiotherapy specifics, including site, timing, dose, and fragmentation pattern, were at the investigator\'s discretion. The primary outcome was dose-limiting toxicity (DLT). From May 2019 to April 2021, 25 patients were enrolled across the dosage groups: 3 in 1 mg/kg, 12 in 3 mg/kg, and 10 in 5 mg/kg. No DLT was observed during the dose escalation. The objective response rate was 41.7% (95%CI 22.1-63.4), while the disease control rate was 87.5% (95%CI 67.6-97.3). At a median follow-up of 11.8 months, the median progression-free survival was 7.8 months (95%CI 5.2-9.7) and median overall survival was 15.9 months (95%CI 8.4-NE). Serious adverse events were reported in 48.0% of patients, predominantly leukopenia (16%), immune-mediated enterocolitis (12%), immune-mediated pneumonitis (8%), and neutropenia (8%). Combining KN046 with chemotherapy and palliative radiotherapy might be feasible, showing a favorable safety profile and notable efficacy in advanced ESCC patients.