Department of Medical Oncology, Laboratory for Medical and Molecular Oncology (LMMO), Vrije Universiteit Brussel (VUB), Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090, Brussels, Belgium.
Department of Radiology, Universitair Ziekenhuis Brussel (UZ Brussel), Laarbeeklaan 101, 1090, Brussels, Belgium.
Cancer Immunol Immunother. 2024 Jul 2;73(9):167. doi: 10.1007/s00262-024-03751-0.
Radiotherapy (RT) synergizes with immune checkpoint blockade (ICB). CD1c(BDCA-1)/CD141(BDCA-3) myeloid dendritic cells (myDC) in the tumor microenvironment are indispensable at initiating effector T-cell responses and response to ICB.
In this phase II clinical trial, anti-PD-1 ICB pretreated oligometastatic patients (tumor agnostic) underwent a leukapheresis followed by isolation of CD1c(BDCA-1)/CD141(BDCA-3) myDC. Following hypofractionated stereotactic body RT (3 × 8 Gy), patients were randomized (3:1). Respectively, in arm A (immediate treatment), intratumoral (IT) ipilimumab (10 mg) and avelumab (40 mg) combined with intravenous (IV) pembrolizumab (200 mg) were administered followed by IT injection of myDC; subsequently, IV pembrolizumab and IT ipilimumab/avelumab were continued (q3W). In arm B (contemporary control arm), patients received IV pembrolizumab, with possibility to cross-over at progression. Primary endpoint was 1-year progression-free survival rate (PFS). Secondary endpoints were safety, feasibility, objective response rate, PFS, and overall survival (OS).
Thirteen patients (10 in arm A, eight non-small cell lung cancer, and five melanoma) were enrolled. Two patients crossed over. One-year PFS rate was 10% in arm A and 0% in arm B. Two patients in arm A obtained a partial response, and one patient obtained a stable disease as best response. In arm B, one patient obtained a SD. Median PFS and OS were 21.8 weeks (arm A) versus 24.9 (arm B), and 62.7 versus 57.9 weeks, respectively. An iatrogenic pneumothorax was the only grade 3 treatment-related adverse event.
SBRT and pembrolizumab with or without IT avelumab/ipilimumab and IT myDC in oligometastatic patients are safe and feasible with a clinically meaningful tumor response rate. However, the study failed to reach its primary endpoint.
Clinicaltrials.gov: NCT04571632 (09 AUG 2020).
2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.
放射治疗（RT）与免疫检查点阻断（ICB）协同作用。肿瘤微环境中的 CD1c（BDCA-1）/CD141（BDCA-3）髓样树突状细胞（myDC）对于启动效应 T 细胞反应和对 ICB 的反应至关重要。
在这项 II 期临床试验中，接受抗 PD-1 ICB 预处理的寡转移患者（肿瘤不可知）进行白细胞分离，然后分离 CD1c（BDCA-1）/CD141（BDCA-3）myDC。在接受分次立体定向体部 RT（3×8 Gy）后，患者随机分组（3:1）。分别在 A 臂（即刻治疗）中，局部给予 ipilimumab（10mg）和avelumab（40mg）联合静脉注射 pembrolizumab（200mg），然后局部注射 myDC；随后，继续静脉注射 pembrolizumab 和局部给予 ipilimumab/avelumab（q3W）。在 B 臂（当代对照臂）中，患者接受静脉注射 pembrolizumab，在进展时可以交叉。主要终点是 1 年无进展生存率（PFS）。次要终点是安全性、可行性、客观缓解率、PFS 和总生存期（OS）。
共纳入 13 名患者（10 名在 A 臂，8 名非小细胞肺癌，5 名黑色素瘤）。两名患者交叉。A 臂的 1 年 PFS 率为 10%，B 臂为 0%。A 臂的 2 名患者获得部分缓解，1 名患者获得最佳反应为稳定疾病。B 臂中 1 名患者获得 SD。中位 PFS 和 OS 分别为 21.8 周（A 臂）与 24.9 周（B 臂），62.7 周与 57.9 周。唯一的 3 级治疗相关不良事件是医源性气胸。
寡转移患者的 SBRT 和 pembrolizumab 联合或不联合局部 avelumab/ipilimumab 和局部 myDC 治疗是安全可行的，具有临床意义的肿瘤反应率。然而，该研究未能达到其主要终点。
Clinicaltrials.gov：NCT04571632（2020 年 8 月 9 日）。EUDRACT：2019-003668-32。注册日期：2019 年 12 月 17 日，修正案 1：2021 年 3 月 6 日，修正案 2：2022 年 2 月 4 日。
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