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。
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.