Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE)
Vaccinia-based oncolytic immunotherapy Pexastimogene Devacirepvec in patients with advanced hepatocellular carcinoma after sorafenib failure: a randomized multicenter Phase IIb trial (TRAVERSE)
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DOI：
10.1080/2162402x.2019.1615817
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发表时间：
2019-06-04
期刊：
影响因子：
7.2
通讯作者：
Burke, J. M.
中科院分区：
文献类型：
--
作者：
Moehler, M.;Heo, J.;Burke, J. M.
Pexastimogene devacirepvec（Pexa-Vec）是一种基于牛痘病毒的溶瘤免疫疗法，旨在优先在肿瘤细胞中复制并破坏肿瘤细胞，同时通过表达GM-CSF刺激抗肿瘤免疫。一项早期的随机IIa期临床试验在主要为索拉非尼初治的肝细胞癌（HCC）中证实了总生存期（OS）获益。这项随机、开放标签的IIb期试验研究了在索拉非尼治疗失败的HCC患者中，Pexa-Vec联合最佳支持治疗（BSC）是否比BSC单药治疗改善了OS（TRAVERSE）。129例患者以2：1的比例随机分配至Pexa-Vec + BSC组与BSC单药组。Pexa-Vec通过单次静脉（IV）输注给药，随后进行最多5次IT注射。主要终点为OS，次要终点包括总有效率（RR）、疾病进展时间（TTP）和安全性。对照组的高脱落率（63%）混淆了基于缓解的终点评估。Pexa-Vec + BSC与BSC单药治疗的中位OS（ITT）分别为4.2和4.4个月（HR，1.19，95% CI：0.78-1.80; p = 0.428）。两个治疗组之间的RR或TTP无差异。Pexa-Vec通常耐受良好。最常见的3级包括发热（8%）和低血压（8%）。观察到对牛痘抗原和HCC相关抗原的免疫应答的诱导。尽管Pexa-Vec具有可耐受的安全性和诱导T细胞应答，但在索拉非尼失败后作为二线治疗并未改善OS。溶瘤病毒的真正潜力可能在于治疗早期疾病阶段的患者，这应该在未来的研究中得到解决。ClinicalTrials.gov：NCT01387555
Pexastimogene devacirepvec (Pexa-Vec) is a vaccinia virus-based oncolytic immunotherapy designed to preferentially replicate in and destroy tumor cells while stimulating anti-tumor immunity by expressing GM-CSF. An earlier randomized Phase IIa trial in predominantly sorafenib-naive hepatocellular carcinoma (HCC) demonstrated an overall survival (OS) benefit. This randomized, open-label Phase IIb trial investigated whether Pexa-Vec plus Best Supportive Care (BSC) improved OS over BSC alone in HCC patients who failed sorafenib therapy (TRAVERSE). 129 patients were randomly assigned 2:1 to Pexa-Vec plus BSC vs. BSC alone. Pexa-Vec was given as a single intravenous (IV) infusion followed by up to 5 IT injections. The primary endpoint was OS. Secondary endpoints included overall response rate (RR), time to progression (TTP) and safety. A high drop-out rate in the control arm (63%) confounded assessment of response-based endpoints. Median OS (ITT) for Pexa-Vec plus BSC vs. BSC alone was 4.2 and 4.4 months, respectively (HR, 1.19, 95% CI: 0.78-1.80; p = .428). There was no difference between the two treatment arms in RR or TTP. Pexa-Vec was generally well-tolerated. The most frequent Grade 3 included pyrexia (8%) and hypotension (8%). Induction of immune responses to vaccinia antigens and HCC associated antigens were observed. Despite a tolerable safety profile and induction of T cell responses, Pexa-Vec did not improve OS as second-line therapy after sorafenib failure. The true potential of oncolytic viruses may lie in the treatment of patients with earlier disease stages which should be addressed in future studies. ClinicalTrials.gov: NCT01387555