Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.
Combining immunotherapy with an epidrug in squamous cell carcinomas of different locations: rationale and design of the PEVO basket trial.
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将免疫疗法与表皮药物相结合治疗不同部位的鳞状细胞癌：PEVO 篮子试验的基本原理和设计。
DOI：
10.1016/j.esmoop.2021.100106
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发表时间：
2021-06
期刊：
影响因子：
7.3
通讯作者：
Le Tourneau C
中科院分区：
文献类型：
--
作者：
de Guillebon E;Jimenez M;Mazzarella L;Betsou F;Stadler P;Peták I;Jeannot E;Chanas L;Servant N;Marret G;Duso BA;Legrand F;Kornerup KN;Bernhart SH;Balogh G;Dóczi R;Filotás P;Curigliano G;Bièche I;Guérin J;Dirner A;Neuzillet C;Girard N;Borcoman E;Larbi Chérif L;Tresca P;Roufai DB;Dupain C;Scholl S;André F;Fernandez X;Filleron T;Kamal M;Le Tourneau C
鳞状细胞癌（SCC）是人类最常见的实体瘤之一。SCC与人乳头瘤病毒相关或无关，具有共同的分子特征。免疫疗法，特别是免疫检查点抑制剂，已被证明可以改善多种癌症类型的总生存期，包括SCC。然而，只有少数患者经历免疫治疗的持久反应。表观遗传调节在逃避肿瘤免疫监视中起主要作用，并赋予对免疫检查点抑制剂的抗性。临床前证据表明，调节表观基因组可能会提高免疫治疗的疗效。我们在此回顾了临床前和临床的基本原理，结合免疫治疗与抗肿瘤药物，并详细介绍了PEVOsq的设计，一个篮子临床试验相结合的pembrolizumab与伏立诺他，组蛋白脱乙酰酶抑制剂，在不同位置的SCC患者。将连续采集血液和肿瘤样本，以确定联合治疗疗效的预测性和药效学生物标志物。我们还介绍了如何管理临床和生物数据，旨在开发一个前瞻性的综合平台，以允许安全和受控地访问项目数据以及进一步开发。不同部位的鳞状细胞癌（SCC）具有相同的分子特征。免疫疗法改善了包括SCC在内的几种癌症的总体生存率。表观遗传调节在免疫治疗抵抗中起主要作用。PEVOsq在几个地点的SCC中评价了派姆单抗/伏立诺他联合治疗。一个集成的平台可确保生成数据的安全优化管理。
Squamous cell carcinomas (SCCs) are among the most frequent solid tumors in humans. SCCs, related or not to the human papillomavirus, share common molecular features. Immunotherapies, and specifically immune checkpoint inhibitors, have been shown to improve overall survival in multiple cancer types, including SCCs. However, only a minority of patients experience a durable response with immunotherapy. Epigenetic modulation plays a major role in escaping tumor immunosurveillance and confers resistance to immune checkpoint inhibitors. Preclinical evidence suggests that modulating the epigenome might improve the efficacy of immunotherapy. We herein review the preclinical and the clinical rationale for combining immunotherapy with an epidrug, and detail the design of PEVOsq, a basket clinical trial combining pembrolizumab with vorinostat, a histone deacetylase inhibitor, in patients with SCCs of different locations. Sequential blood and tumor sampling will be collected in order to identify predictive and pharmacodynamics biomarkers of efficacy of the combination. We also present how clinical and biological data will be managed with the aim to enable the development of a prospective integrative platform to allow secure and controlled access to the project data as well as further exploitations. Squamous cell carcinomas (SCCs) of different locations share molecular features. Immunotherapy improves overall survival in several cancers including SCCs. Epigenetic modulation plays a major role in resistance to immunotherapy. PEVOsq evaluates pembrolizumab/vorinostat combination in SCCs of several locations. An integrative platform ensures secured optimal management of generated data.
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影响因子：
64.8
作者：
Guerriero JL;Sotayo A;Ponichtera HE;Castrillon JA;Pourzia AL;Schad S;Johnson SF;Carrasco RD;Lazo S;Bronson RT;Davis SP;Lobera M;Nolan MA;Letai A
通讯作者：
Letai A
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Wong KK
影响因子：
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通讯作者：
Van Waes C
影响因子：
45.3
作者：
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通讯作者：
Varga, Andrea
影响因子：
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