重组痘苗病毒联合cemiplimab治疗肾细胞癌的研究
Pexa-Vec（胸苷激酶失活痘苗病毒加 GM-CSF）联合 Cemiplimab（REGN2810；抗 PD-1）治疗转移性或不可切除肾病患者的 1b/2a 期剂量递增和安全性/疗效评估研究细胞癌 (RCC)
研究概览
详细说明
For Pexa-Vec IV infusions (Part 1 / Part 2: Arm C and Arm D): Day -7, 1, 8, and 15), patients allocated to Part 1 or Part 2: Arm C or Arm D will receive an IV infusion of Pexa-Vec in approximately 250 mL buffered saline.
For Pexa-Vec IT Injections (Part 2 Arm A + Arm B), patients in Part 2, Arm A (and those in Arm B who progress on Cemiplimab monotherapy) will receive an IT injection of Pexa-Vec in a volume of buffered saline dependent on size of tumor(s).
For administration of Cemiplimab, Cemiplimab will be administered at a dose of 350 mg IV infusion over 30 minutes (±10 minutes) every 3 weeks per manufactures guidelines.
研究类型
注册 (实际的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习地点
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Bedford Park、澳大利亚、SA5042
- Site 2632 Flinders Medical Centre
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Camperdown、澳大利亚
- Site 2631
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California
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Irvine、California、美国、92868
- Site 2644 University of California, Irvine
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Florida
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Miami、Florida、美国、33136
- Site 2641 University of Miami
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Missouri
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St Louis、Missouri、美国、63141
- Site 2643 Washington University
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Montana
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Billings、Montana、美国、59101
- Site 2642 Billings Clinic
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Ohio
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Columbus、Ohio、美国、43201
- Site 2646 The Ohio State University
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Daegu、韩国、41404
- Site 2612 Kyungpook National University Chilgok Hospital
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Daejeon、韩国、35015
- Site 2616 Chungnam National University Hospital
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Gwangju、韩国、58128
- Site 2618 Chonnam National University Hwasun Hospital
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Incheon、韩国
- Site 2622 Gachon University Gil Medical Center
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Jinju、韩国、52727
- Site 2614 Gyeongsang National University Hospital
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Pusan、韩国、49201
- Site 2613 Dong-A University Hospital
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Pusan、韩国、49241
- Site 2619 Pusan National University Hospital
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Seongnam、韩国、35015
- Site 2617 CHA University, CHA Bundang Medical Center
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Seongnam-si、韩国、13620
- Site 2620 Seoul National University Bundang Hospital
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Seoul、韩国、02841
- Site 2615 Korea University Anam Hospital
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Seoul、韩国、03722
- Site 2610 Severance Hospital, Yonsei University Health System
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Suwon、韩国、16499
- Site 2623 Ajou University Hospital
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Wŏnju、韩国、50612
- Site 2625 Wonju Severance Christian Hospital
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Yangsan、韩国、50612
- Site 2624 Pusan National University Yangsan Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
描述
纳入标准：
- 经组织学或细胞学证实的转移性或不可切除的透明细胞肾细胞癌 (ccRCC)
仅第 2 部分 D 组：患者必须对抗 PD-1 或抗 PD-L1（作为单一疗法或与其他批准的检查点抑制剂或根据其批准的标签的靶向疗法联合使用）耐药，并且患者必须满足所有以下标准：
- 接受了至少 6 周的经批准的抗 PD-1 或抗 PD-L1 治疗（根据提供临床地点的国家/地区的标签给药）。 不允许只有抗 PD-L1 的历史。
- 抗 PD-1 或抗 PD-L1 后的疾病进展将根据 RECIST 1.1 定义。 在没有快速临床进展的情况下，进行性疾病的初步证据将通过第二次评估确认，从第一次记录的进行性疾病之日起不少于 4 周。 （该决定由研究者做出；申办者将收集成像扫描以进行回顾性分析。 一旦确认进行性疾病，进行性疾病文件的初始日期将被视为疾病进展的日期）。
- 在最后一次抗 PD-1 或抗 PD-L1 给药后 12 周内记录到疾病进展。 接受抗 PD-1 或抗 PD-L1 药物再治疗或维持治疗的患者将被允许进入研究，只要在最后一次治疗日期后的 12 周内有记录的疾病进展。
- 未对 RCC 进行全身治疗或在之前的全身治疗后进展或不能耐受。
- 基于 RECIST 1.1 标准的可测量疾病。 位于先前照射区域的肿瘤病变如果已证明在此类病变中进展，则被认为是可测量的
- 70-100 的 Karnofsky 性能状态
- 年龄≥20岁（或当地同意的适当年龄）
- 足够的血液学、肝和肾功能
排除标准：
- 由于基础疾病（例如人类免疫缺陷病毒 [HIV]/获得性免疫缺陷综合症 [AIDS]）和/或免疫抑制药物（包括大剂量皮质类固醇）导致的已知严重免疫缺陷
- 仅第 2 部分：A、B、C 组：之前接受过任何抗癌免疫疗法治疗，包括使用抗 PD-1、抗 PD-L1 或抗 PD-L2 药物（之前的 IL-2 或干扰素）治疗允许）。 对于第 1 部分：如果患者不能耐受抗 PD-1 或抗 PD-L1 靶向治疗，则被排除在外
- 研究治疗后 4 周内进行过大手术（允许进行小手术）
- 需要事先治疗的持续严重炎症性皮肤病
- 需要事先治疗的湿疹病史
- 肿瘤侵犯主要血管结构（例如颈动脉）或其他关键解剖结构（例如肺气道）或活的中枢神经系统恶性肿瘤
- 有临床意义和/或迅速积聚的腹水、心包和/或胸腔积液。
- 在过去的 12 个月内有症状的心血管疾病，包括但不限于严重的冠状动脉疾病（例如，需要血管成形术或支架置入术）或充血性心力衰竭。
- 无症状的心血管疾病（当前或既往病史），除非已获得心脏病学咨询和参与研究的许可。
- 在所有 Pexa-Vec 治疗前 48 小时和治疗后 48 小时内无法暂停抗高血压药物治疗
- 使用任何 Pexa-Vec 剂量前 14 天内不能停用的干扰素/聚乙二醇化干扰素 (PEG-IFN) 或利巴韦林
- 已知活动性乙型肝炎或丙型肝炎
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的：Part 1, Dose escalation 3 x 10^8 pfu
Pexa-Vec will be administered via IV infusion at a dose of 3 x 10^8 pfu once per week for 4 treatments. Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 3 x 10^8 pfu. Cemiplimab will be administered via IV infusion every 3 weeks. |
Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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实验性的：Part 1, Dose escalation 1 x 10^9 pfu
Pexa-Vec will be administered via IV infusion at a dose of 1 x 10^9 pfu once per week for 4 treatments.
Based on the occurrence of dose-limiting toxicities, patients may subsequently be enrolled to receive Pexa-Vec on the same schedule at a dose of 1 x 10^9 pfu.
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Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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实验性的：Part 2-Arm A, Pexa-Vec (IT) and Cemiplimab
Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. Pexastimogene Devacirepvec (Pexa-Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1) |
Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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实验性的：Part 2-Arm B, Cemiplimab
Cemiplimab will be administered via IV infusion every 3 weeks. At disease progression, Pexa-Vec will be administered via IT (intratumoral) injection every 2 weeks for 3 treatments. Cemiplimab will continue every 3 weeks. Pexastimogene Devacirepvec (Pexa-Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1) |
Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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实验性的：Part 2-Arm C, Pexa-Vec (IV) and Cemiplimab
Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. Pexastimogene Devacirepvec (Pexa-Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1) |
Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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实验性的：Part 2-Arm D, Pexa-Vec (IV) and Cemiplimab
Pexa-Vec will be administered via IV infusion once per week for 4 treatments. Cemiplimab will be administered via IV infusion every 3 weeks. Pexastimogene Devacirepvec (Pexa-Vec): Pexa-Vec is a vaccinia virus based oncolytic immunotherapy designed to stimulate the immune system following infection and replication within tumor cells Cemiplimab: Cemiplimab is a monoclonal antibody to Programmed Death-1 (PD-1) |
Pexa-Vec 是一种基于痘苗病毒的溶瘤免疫疗法，旨在刺激肿瘤细胞内感染和复制后的免疫系统
其他名称：
Cemiplimab 是一种针对程序性死亡 1 (PD-1) 的单克隆抗体
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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Number and Percentage of Participants With Adverse Events From Pexa-Vec Administered by IV Infusions or IT Injections in Combination With IV Cemiplimab
大体时间：Through study completion without survival follow-up period, an average of 1 year
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Safety will be determined by assessing the incidence, severity, and frequency of all treatment-emergent adverse events (TEAEs), Grade 3 or greater AEs, serious adverse events (SAEs), laboratory toxicity, AEs requiring discontinuation of study agent(s), and deaths.
The severity of all adverse events and laboratory abnormalities is assessed and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.
Safety is monitored from the first dose throughout the treatment period (up to a maximum of 1 year) and up to 28 days after the last dose of study treatment.
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Through study completion without survival follow-up period, an average of 1 year
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Overall Response Rate
大体时间：Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months.
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Overall response rate (ORR) is defined as the proportion of patients whose best overall responses either complete response (CR) or partial response (PR). The best overall response is the best response recorded from the randomization until disease progression. Proportions of patients with a best overall response of CR, disappearance of all target tumors; or PR, at least 30% decrease in the sum of longest diameter of target tumors will be presented by treatment arm along with exact 95% CIs. Analyses will be performed based on central assessments using RECIST v1.1. |
Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months.
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Number of Participants With Dose Limiting Toxicities of Pexa-Vec Administered by IV Infusions in Combination With Cemiplimab (Part 1 Only)
大体时间：The 29-day cycle of therapy
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Dose-limiting toxicity (DLT) was assessed to determine the maximum tolerated dose (MTD) or maximum feasible dose (MFD) of Pexa-Vec.
Patients were observed for DLTs during the IV treatment phase through Day 29.
DLTs are evaluated based on the severity and frequency of adverse events and laboratory abnormalities using NCI CTCAE Version 5.0.
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The 29-day cycle of therapy
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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Progression Free Survival
大体时间：Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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Defined as the date of the first study treatment to the date of first documented radiographic tumor progression or death due to any cause, whichever occurs first (RECIST v1.1).
Progression free survival will be presented descriptively using Kaplan-Meier curves.
Summary statistics from the Kaplan-Meier distributions will be determined, including median PFS and 25% and 75% quartiles with corresponding 95% CIs.
The proportions of patients.
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Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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Disease Control Rate
大体时间：Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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Defined as the proportion of patients whose best overall response is either complete response (CR), partial response (PR), or stable disease (SD).
(RECIST v1.1)
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Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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Overall Survival
大体时间：Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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Overall survival is defined as the time from first study treatment until death from any cause.
For patients not known to have died at the time of the analysis, overall survival will be censored on the date they were last known to be alive.
If a patient withdraws early, overall survival will not be censored at the date of withdrawal unless this is the date they were last known to be alive.
Date of death will be obtained from the death certificate (preferable) or from a written statement from the primary care or attending physician, or from death registry data.
Additionally, for censored date, the latest date of (in the following order): End of Treatment visit(EOT) / Last Radiologic Timepoint(LastRTP) / End of Study(EOS) / Last Drug Date(D.LastDrug) / before cutoff date(2023-02-16) is the censored date.
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Every 9 weeks until documented progression or discontinuation beyond documented progression. After 1 year, every 12 weeks from EOT visit, up to 36 months
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合作者和调查者
出版物和有用的链接
有用的网址
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
肾细胞癌的临床试验
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Taichung Veterans General Hospital完全的心脏毒性 | 非小细胞肺癌（MeSH术语：Carcinoma, Non-Small-Cell Lung） | 药物相关副作用和不良反应（MeSH术语） | 表皮生长因子受体酪氨酸激酶抑制剂台湾
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Fondazione del Piemonte per l'Oncologia招聘中乳腺癌 | 卵巢癌 | 结直肠癌 | 黑色素瘤（皮肤癌） | 非小细胞肺癌（MeSH术语：Carcinoma, Non-Small-Cell Lung）意大利
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Lakefront Biotherapeutics NV终止复发/难治性 B 细胞非霍奇金淋巴瘤 | 淋巴瘤非霍奇金＆amp;＃39; s b-cell美国, 比利时, 荷兰, 芬兰
Pexastimogene Devacirepvec (Pexa-Vec)的临床试验
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National Cancer Institute (NCI)完全的
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Transgene终止
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SillaJen, Inc.完全的肝细胞癌 (HCC)美国, 加拿大, 澳大利亚, 中国, 法国, 德国, 香港, 以色列, 意大利, 新西兰, 葡萄牙, 新加坡, 台湾, 泰国, 英国, 韩国
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Lee's Pharmaceutical Limited招聘中一线治疗失败的局部进展或转移性黑色素瘤中国
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Jennerex BiotherapeuticsSolving Kids' Cancer完全的
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Centre Leon BerardTransgene完全的
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Institut BergoniéMerck Sharp & Dohme LLC; National Cancer Institute, France; Transgene; Fondation ARC招聘中