PDF(Pubmed)
Abstract：
Malignant pleural mesothelioma (MPM) is an aggressive cancer with a very poor prognosis. Recently, immune checkpoint inhibition (ICI) has taken center stage in the currently ongoing revolution that is changing standard-of-care treatment for several malignancies, including MPM. As multiple arguments and accumulating lines of evidence are in support of the existence of a therapeutic synergism between chemotherapy and immunotherapy, as well as between different classes of immunotherapeutics, we designed a multicenter, single-arm, phase I/II trial in which both programmed-death-ligand 1 (PD-L1) inhibition and dendritic cell (DC) vaccination are integrated in the first-line conventional platinum/pemetrexed-based treatment scheme for epithelioid MPM patients (Immuno-MESODEC, ClinicalTrials.gov identifier NCT05765084). Fifteen treatment-naïve patients with unresectable epithelioid subtype MPM will be treated with four 3-weekly (±3 days) chemo-immunotherapy cycles. Standard-of-care chemotherapy consisting of cisplatinum (75mg/m2) and pemetrexed (500mg/m2) will be supplemented with the anti-PD-L1 antibody atezolizumab (1200 mg) and autologous Wilms\' tumor 1 mRNA-electroporated dendritic cell (WT1/DC) vaccination (8-10 x 106 cells/vaccination). Additional atezolizumab (1680 mg) doses and/or WT1/DC vaccinations (8-10 x 106 cells/vaccination) can be administered optionally following completion of the chemo-immunotherapy scheme. Follow-up of patients will last for up to 90 days after final atezolizumab administration and/or WT1/DC vaccination or 24 months after diagnosis, whichever occurs later. The trial\'s primary endpoints are safety and feasibility, secondary endpoints are clinical efficacy and immunogenicity. This phase I/II trial will evaluate whether addition of atezolizumab and WT1/DC vaccination to frontline standard-of-care chemotherapy for the treatment of epithelioid MPM is feasible and safe. If so, this novel combination strategy should be further investigated as a promising advanced treatment option for this hard-to-treat cancer.
摘要：
恶性胸膜间皮瘤（MPM）是一种侵袭性癌症，预后极差。最近,免疫检查点抑制（ICI）在目前正在进行的革命中占据了中心位置，这场革命正在改变几种恶性肿瘤的标准治疗方法，包括MPM。由于多种论据和越来越多的证据支持化疗和免疫治疗之间存在治疗协同作用，以及不同类别的免疫治疗剂，我们设计了一个多中心,单臂,I/II期试验，其中程序性死亡配体1（PD-L1）抑制和树突状细胞（DC）疫苗接种均纳入上皮样MPM患者的一线常规铂/培美曲塞治疗方案（Immuno-MESODEC，ClinicalTrials.gov标识符NCT05765084）。15名不可切除的上皮样亚型MPM的未治疗患者将接受4个3周（±3天）的化学免疫疗法周期治疗。由顺铂（75mg/m2）和培美曲塞（500mg/m2）组成的标准治疗化疗将补充抗PD-L1抗体阿替珠单抗（1200mg）和自体Wilms肿瘤1mRNA电穿孔的树突状细胞（WT1/DC）疫苗接种（8-10×106个细胞/疫苗接种）。在完成化学免疫疗法方案后,可以任选地施用额外的阿替珠单抗(1680mg)剂量和/或WT1/DC疫苗接种(8-10x106个细胞/疫苗接种)。患者的随访将在最终阿特珠单抗给药和/或WT1/DC疫苗接种后持续90天或诊断后24个月，以后发生的。试验的主要终点是安全性和可行性，次要终点是临床疗效和免疫原性.这项I/II期试验将评估在治疗上皮样MPM的一线标准化疗中添加阿特珠单抗和WT1/DC疫苗是否可行和安全。如果是,对于这种难以治疗的癌症,这种新颖的联合治疗策略应作为一种有前景的高级治疗选择进行进一步研究.
