Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy.
Rescuing Cancer Immunity by Plasma Exchange in Metastatic Melanoma (ReCIPE-M1): protocol for a single-institution, open-label safety trial of plasma exchange to clear sPD-L1 for immunotherapy.
复制标题
DOI：
10.1136/bmjopen-2021-050112
复制
发表时间：
2022-05-12
期刊：
影响因子：
2.9
通讯作者：
Orme, Jacob J.
中科院分区：
文献类型：
--
作者：
Davidson, Tara M.;Foster, Nathan;Lucien, Fabrice;Markovic, Svetomir;Dong, Haidong;Winters, Jeffrey L.;Park, Sean S.;Orme, Jacob J.
转移性黑色素瘤患者依赖PD-（L）1免疫治疗，但只有三分之一的患者经历治疗反应，所有初始反应者最终都会产生耐药性。黑色素瘤患者外周血中表达程序性死亡配体1（evPD-L1）和可溶性程序性死亡配体1（sPD-L1）的肿瘤源性细胞外囊泡限制了PD-（L）1免疫治疗，并与不良生存期相关。治疗性血浆置换（TPE）可清除免疫抑制性evPD-L1和sPD-L1。我们假设TPE可以挽救和恢复抗黑素瘤免疫力。在这项两组研究中，将招募60例接受检查点抑制治疗后进展的转移性黑色素瘤患者。所有患者将在第1-5天接受放射治疗（至少一个可测量的病变将不接受放射治疗），并在第8天和每2-3周一次按照标准治疗进行检查点抑制。基线sPD-L1水平≥1.7 ng/mL且具有足够临床能力的患者将入组TPE干预组，除标准治疗放疗和免疫治疗外，还将在第5-7天接受TPE。其他患者将留在标准治疗组，研究的主要终点是评估安全性。次要终点包括sPD-L1和evPD-L1的动力学以及根据RECIST（实体瘤疗效评价标准）标准的临床疗效。研究注册于ClinicalTrials.gov（NCT 04581382）。本试验已获得马约诊所机构审查委员会的批准。它将评估TPE在改善PD-（L）1抑制剂免疫治疗黑色素瘤的结局方面的安全性和可行性。数据将保存在一个安全的数据库中，其中包含去识别的患者信息。数据将在同行评审期刊上发表时共享，而无需专业作者的帮助。如果成功，这项试验将为II期研究奠定基础，这些研究将包括使用PD-（L）1抑制剂治疗的癌症，这些癌症可能从TPE中受益，如肾癌，膀胱癌和肺癌。NCT 04581382。
Patients with metastatic melanoma rely on PD-(L)1 immunotherapy, but only one-third of patients experience treatment response and all initial responders eventually develop resistance. Tumour-derived extracellular vesicles expressing Programmed death ligand 1 (evPD-L1) and soluble Programmed death ligand 1 (sPD-L1) in peripheral blood of patients with melanoma limit PD-(L)1 immunotherapy and correlate with poor survival. Therapeutic plasma exchange (TPE) removes immunosuppressive evPD-L1 and sPD-L1. We hypothesise that TPE may rescue and restore antimelanoma immunity. In this two-arm study, 60 patients with metastatic melanoma progressing on checkpoint inhibition will be accrued. All patients will undergo radiotherapy on days 1–5 (at least one measurable lesion will not be irradiated) and ongoing checkpoint inhibition on day 8 and every 2–3 weeks per standard of care. Patients with baseline sPD-L1 level of ≥1.7 ng/mL and adequate clinical capacity will be enrolled in the TPE intervention arm and will undergo TPE on days 5–7, in addition to standard of care radiotherapy and immunotherapy. Other patients will remain in the standard of care arm. The primary endpoint of the study is to evaluate safety. Secondary endpoints include kinetics of sPD-L1 and evPD-L1 and clinical response by RECIST (Response Evaluation Criteria in Solid Tumors) criteria. Study registered at ClinicalTrials.gov (NCT04581382). This trial has been approved by the Mayo Clinic Institutional Review Board. It will assess the safety and feasibility of TPE in improving outcomes for PD-(L)1 inhibitor immunotherapy in melanoma. Data will be maintained on a secure database with deidentified patient information. Data will be shared on publication in a peer-reviewed journal without the aid of professional writers. If successful, this trial will lay the ground for phase II studies that will include cancer treated with PD-(L)1 inhibitors which may benefit from TPE such as renal, bladder and lung cancers. NCT04581382.
登录
查看更多内容
影响因子：
--
作者：
Ha H;Nam AR;Bang JH;Park JE;Kim TY;Lee KH;Han SW;Im SA;Kim TY;Bang YJ;Oh DY
通讯作者：
Oh DY
影响因子：
158.5
作者：
Robert, Caroline;Schachter, Jacob;Ribas, Antoni
通讯作者：
Ribas, Antoni
开发夹心 ELISA，用于评估不同年龄的人血清以及 PD-L1 细胞系上清液中的可溶性 PD-L1 (CD274)。
影响因子：
3.8
作者：
Chen, Yongjing;Wang, Qin;Zhang, Xueguang
通讯作者：
Zhang, Xueguang
影响因子：
5.1
作者：
Zheng, Zhixue;Bu, Zhaode;Ji, Jiafu
通讯作者：
Ji, Jiafu
影响因子：
2.9
作者：
Zhang J;Gao J;Li Y;Nie J;Dai L;Hu W;Chen X;Han J;Ma X;Tian G;Wu D;Shen L;Fang J
通讯作者：
Fang J