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Abstract：
BACKGROUND: 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.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Clinicaltrials.gov: NCT04571632 (09 AUG 2020).
UNASSIGNED: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.
METHODS: 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).
RESULTS: 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.
CONCLUSIONS: 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.
BACKGROUND: Clinicaltrials.gov: NCT04571632 (09 AUG 2020).
UNASSIGNED: 2019-003668-32. Date of registration: 17 DEC 2019, amendment 1: 6 MAR 2021, amendment 2: 4 FEB 2022.
摘要：
背景：放疗（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）在启动效应T细胞反应和对ICB的反应中是必不可少的。
方法：在这项II期临床试验中，抗PD-1ICB预处理的寡转移患者(肿瘤无关者)接受了白细胞去除术,然后分离CD1c(BDCA-1)+/CD141(BDCA-3)+myDC.在低分割立体定向体RT（3×8Gy）之后，患者被随机分组(3:1).分别,在手臂A（立即治疗），肿瘤内（IT）ipilimumab（10mg）和avelumab（40mg）联合静脉（IV）pembrolizumab（200mg），然后IT注射myDC;随后，继续静脉注射派姆单抗和ITipilimumab/avelumab（q3W）。在B臂(当代控制臂)中，患者接受静脉注射pembrolizumab，有可能在进展中交叉。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,客观反应率，PFS,总生存率（OS）。
结果：13例患者（A组10例，八种非小细胞肺癌，和五个黑色素瘤）被登记。两个病人交叉。A臂的一年PFS率为10％，B臂为0％。一名患者获得了稳定的疾病作为最佳反应。在B臂,一名患者获得了SD。中位PFS和OS分别为21.8周（A组）和24.9周（B组），和62.7对57.9周，分别。医源性气胸是唯一的3级治疗相关不良事件。
结论：SBRT和派姆单抗联合或不联合ITavelumab/ipilimumab和ITmyDC在寡转移患者中是安全可行的，具有临床意义的肿瘤反应率。然而,该研究未能达到主要终点.
背景：临床试验：NCT04571632（2020年8月9日）。
■2019-003668-32。注册日期：2019年12月17日，2021年3月1:6日，2022年2月2:4日。
方法：在这项II期临床试验中，抗PD-1ICB预处理的寡转移患者(肿瘤无关者)接受了白细胞去除术,然后分离CD1c(BDCA-1)+/CD141(BDCA-3)+myDC.在低分割立体定向体RT（3×8Gy）之后，患者被随机分组(3:1).分别,在手臂A（立即治疗），肿瘤内（IT）ipilimumab（10mg）和avelumab（40mg）联合静脉（IV）pembrolizumab（200mg），然后IT注射myDC;随后，继续静脉注射派姆单抗和ITipilimumab/avelumab（q3W）。在B臂(当代控制臂)中，患者接受静脉注射pembrolizumab，有可能在进展中交叉。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,客观反应率，PFS,总生存率（OS）。
结果：13例患者（A组10例，八种非小细胞肺癌，和五个黑色素瘤）被登记。两个病人交叉。A臂的一年PFS率为10％，B臂为0％。一名患者获得了稳定的疾病作为最佳反应。在B臂,一名患者获得了SD。中位PFS和OS分别为21.8周（A组）和24.9周（B组），和62.7对57.9周，分别。医源性气胸是唯一的3级治疗相关不良事件。
结论：SBRT和派姆单抗联合或不联合ITavelumab/ipilimumab和ITmyDC在寡转移患者中是安全可行的，具有临床意义的肿瘤反应率。然而,该研究未能达到主要终点.
背景：临床试验：NCT04571632（2020年8月9日）。
■2019-003668-32。注册日期：2019年12月17日，2021年3月1:6日，2022年2月2:4日。
