Neoadjuvant Study of the effect of Intratumoural and Intravenous Pexastimogene Devacirepvec (Pexa-Vec) on CD8-based anti-tumour response in Prostate Cancer Prior to Radical Prostatectomy

开始日期2023-05-05

申办/合作机构

Royal Melbourne Hospital

CTR20210605

/ Terminated临床1/2期

一线治疗失败后局部进展或转移性黑色素瘤中Pexa-Vec（痘苗GM-CSF/TK灭活病毒）联合重组全人抗PD-L1单克隆抗体（ZKAB001）的Ib/II期、开放、对照临床研究

主要目的： Ib期：评价在一线治疗失败的局部进展或转移性黑色素瘤患者中Pexa-Vec联合ZKAB001治疗的安全性和II期推荐剂量（RP2D）； II期：评价在一线治疗失败的局部进展或转移性黑色素瘤患者中ZKAB001联合Pexa-Vec II期推荐剂量或ZKAB001单药治疗的客观缓解率（ORR）和无进展生存期（PFS）。次要目的： 1) ZKAB001联合Pexa-Vec及ZKAB001单药治疗一线治疗失败的局部进展或转移性黑色素瘤患者的总生存期（OS）、疾病控制率（DCR）和缓解持续时间（DOR）； 2) 评价Pexa-Vec联合ZKAB001治疗一线治疗失败的局部进展或转移性黑色素瘤患者的安全性； 3) 评价肿瘤组织PD-L1的表达水平与临床效应关系； 4) 评价Pexa-vec治疗前后肿瘤组织免疫微环境的变化（CD8+表达水平）。

开始日期2021-09-27

申办/合作机构

兆科（广州）肿瘤药物有限公司

NCT04849260

/ Unknown status临床1/2期

Phase Ib/II, Open Label, Controlled Clinical Study of Pexa-Vec (Vaccinia GM CSF / Thymidine Kinase-Deactivated Virus) Combined With Recombinant Whole Human Anti-PD-L1 Monoclonal Antibody (ZKAB001) in Metastatic Melanoma After First-line Treatment Failure

The study will be divided into two stages: phase Ib and phase II. The safety and phase II recommended dose (RP2D) of Pexa-Vec combined with ZKAB001 in patients with local progression of failed first-line treatment or metastatic melanoma will be evaluated in phase Ib.
Objective response rate (ORR) and progression-free survival (PFS) of ZKAB001 combined with RP2D's Pexa-Vec or ZKAB001 monotherapy in patients with local progression or metastatic melanoma will be evaluated in phase II.

开始日期2021-08-26

申办/合作机构

李氏大药厂控股有限公司

100 项与 Pexastimogene devacirepvec 相关的临床结果

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100 项与 Pexastimogene devacirepvec 相关的转化医学

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100 项与 Pexastimogene devacirepvec 相关的专利（医药）

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项与 Pexastimogene devacirepvec 相关的文献（医药）

2024-01-01·Liver Cancer

PHOCUS: A Phase 3, Randomized, Open-Label Study of Sequential Treatment with Pexa-Vec (JX-594) and Sorafenib in Patients with Advanced Hepatocellular Carcinoma

Article

作者: Lusky, Monika ; Gane, Edward ; Qin, Shukui ; Borad, Mitesh J ; Pelusio, Adina ; Luca, Angelo ; Burke, James ; Chao, Yee ; Breitbach, Caroline ; Agathon, Delphine ; Heo, Jeong ; Erinjeri, Joseph ; Abou-Alfa, Ghassan K ; Galle, Peter R

Introduction: Intratumoral administration of pexa-vec (pexastimogene devacirepvec), an oncolytic and immunotherapeutic vaccinia virus, given to patients with hepatocellular carcinoma (HCC), is associated with both local and distant tumor responses. We hypothesized subsequent treatment with sorafenib could demonstrate superior efficacy. Methods: This random phase III open-label study evaluated the sequential treatment with pexa-vec followed by sorafenib compared to sorafenib in patients with advanced HCC and no prior systemic treatment. The primary endpoint is overall survival (OS). Key secondary endpoints included time to progression (TTP), progression-free survival, overall response rate (ORR), and disease control rate (DCR). Safety was assessed in all patients who received ≥1 dose of study treatment. Results: The study was conducted at 142 sites in 16 countries. From December 30, 2015, to the interim analysis on August 2, 2019, 459 patients were randomly assigned (pexa-vec plus sorafenib: 234, sorafenib: 225). At the interim analysis, the median OS was 12.7 months (95% CI: 9.89, 14.95) in the pexa-vec plus sorafenib arm and 14.0 months (95% CI: 11.01, 18.00) in the sorafenib arm. This led to the early termination of the study. The median TTP was 2.0 months (95% CI: 1.77, 2.96) and 4.2 months (95% CI: 2.92, 4.63); ORR was 19.2% (45 patients) and 20.9% (47 patients); and DCR was 50.0% (117 patients) and 57.3% (129 patients) in the pexa-vec plus sorafenib and sorafenib arms, respectively. Serious adverse events were reported in 117 (53.7%) patients in the pexa-vec plus sorafenib and 77 (35.5%) patients in the sorafenib arm. Liver failure was the most frequently reported in both groups. Conclusion: Sequential pexa-vec plus sorafenib treatment did not demonstrate increased clinical benefit in advanced HCC and fared worse compared to sorafenib alone. The advent of the added value of checkpoint inhibitors should direct any further development of oncolytic virus therapy strategies.

2023-02-01·Journal for immunotherapy of cancer

Phase I/II study of PexaVec in combination with immune checkpoint inhibition in refractory metastatic colorectal cancer

Article

作者: Juburi, Israa ; Myojin, Yuta ; Hrones, Donna Mabry ; Cam, Maggie ; Redd, Bernadette ; Homan, Philip ; Greten, Tim F ; Figg, William D ; Hernandez, Jonathan M ; Coffman, Kelley ; Xie, Changqing ; Levy, Elliot B ; Duffy, Austin G ; Wang, Sophie ; Kleiner, David E ; Hewitt, Stephen M ; Monge, Cecilia ; Ruf, Benjamin ; Steinberg, Seth M ; Wood, Bradford J

Background:

Oncolytic immunotherapy represents a unique therapeutic platform for the treatment of cancer. Here, we evaluated the safety and efficacy of the combination of pexastimogene devacirepvec (PexaVec) plus durvalumab (anti-programmed death ligand 1) with and without tremelimumab (anti-cytotoxic T-lymphocyte associated protein 4) in patients with standard chemotherapy refractory mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC) in a phase I/II trial.

Methods:

Adult patients with histologically confirmed advanced pMMR mCRC, who had progressed on at least two prior lines of systemic chemotherapy were studied in four cohorts. Patients received four doses of PexaVec IV at a dose of 3×108 plaque forming units (pfu) (dose level 1) or 1×109 pfu (dose level 2) every 2 weeks. Twelve days after the first PexaVec administration, patients received either 1500 mg of durvalumab every 28 days alone or an additional single dose of 300 mg tremelimumab on day 1. Responses were assessed every 8 weeks by CT or MRI. AEs were recorded. The primary endpoints were safety and feasibility. Secondary endpoints included progression-free survival (PFS) and overall survival. Paired tumor samples and peripheral blood were collected to perform immune monitoring.

Results:

Thirty-four patients with mCRC enrolled on to the study: 16 patients in the PexaVec/durvalumab cohorts and 18 patients in the PexaVec/durvalumab/tremelimumab cohorts. Overall, the combination of PexaVec plus immune checkpoint inhibitors did not result in any unexpected toxicities. Most common toxicities observed were fever and chills after PexaVec infusion. Two cases of grade 3 colitis, one case of a grade 2 myositis and one case of grade 3 hypotension resulted in discontinuation of immune checkpoint inhibitor and PexaVec treatment, respectively. The median PFS in the PexaVec/durvalumab/tremelimumab cohorts was 2.3 months (95% CI: 2.2 to 3.2 months) vs 2.1 months (95% CI: 1.7 to 2.8 months; p=0.57) in the PexaVec/durvalumab cohorts. Flow cytometry analysis of peripheral blood mononuclear cells revealed an increase in Ki67+CD8+ T cells on treatment.

Conclusion:

PexaVec in combination with durvalumab and tremelimumab is safe and tolerable. No unexpected toxicities were observed. The combination of PexaVec/durvalumab/tremelimumab demonstrated potential clinical activity in patients with pMMR mCRC, but further studies are needed to identify the predictive biomarkers.

Trial registration number:

NCT03206073.

2023-01-01·Journal for immunotherapy of cancer

Generation of novel oncolytic vaccinia virus with improved intravenous efficacy through protection against complement-mediated lysis and evasion of neutralization by vaccinia virus-specific antibodies

Article

作者: Yoo, Jiyoon ; Shin, Suk-kyung ; Jung, Byung-Jin ; Jeon, Yun-Hui ; Lee, Namhee ; Oh, Keunhee ; Lee, Songyi ; Lee, Dong-Sup ; Hong, Yun-Kyoung ; Park, Mi-Ju

Background:

Oncolytic virus immunotherapy has revolutionized cancer immunotherapy by efficiently inducing both oncolysis and systemic immune activation. Locoregional administration has been used for oncolytic virus therapy, but its applications to deep-seated cancers have been limited. Although systemic delivery of the oncolytic virus would maximize viral immunotherapy’s potential, this remains a hurdle due to the rapid removal of the administered virus by the complement and innate immune system. Infected cells produce some vaccinia viruses as extracellular enveloped virions, which evade complement attack and achieve longer survival by expressing host complement regulatory proteins (CRPs) on the host-derived envelope. Here, we generated SJ-600 series oncolytic vaccinia viruses that can mimic complement-resistant extracellular enveloped virions by incorporating human CRP CD55 on the intracellular mature virion (IMV) membrane.

Methods:

The N-terminus of the human CD55 protein was fused to the transmembrane domains of the six type I membrane proteins of the IMV; the resulting recombinant viruses were named SJ-600 series viruses. The SJ-600 series viruses also expressed human granulocyte-macrophage colony-stimulating factor (GM-CSF) to activate dendritic cells. The viral thymidine kinase (J2R) gene was replaced by genes encoding the CD55 fusion proteins and GM-CSF.

Results:

SJ-600 series viruses expressing human CD55 on the IMV membrane showed resistance to serum virus neutralization. SJ-607 virus, which showed the highest CD55 expression and the highest resistance to serum complement-mediated lysis, exhibited superior anticancer activity in three human cancer xenograft models, compared with the control Pexa-Vec (JX-594) virus, after single-dose intravenous administration. The SJ-607 virus administration elicited neutralizing antibody formation in two immunocompetent mouse strains like the control JX-594 virus. Remarkably, we found that the SJ-607 virus evades neutralization by vaccinia virus-specific antibodies.

Conclusion:

Our new oncolytic vaccinia virus platform, which expresses human CD55 protein on its membrane, prolonged viral survival by protecting against complement-mediated lysis and by evading neutralization by vaccinia virus-specific antibodies; this may provide a continuous antitumor efficacy until a complete remission has been achieved. Such a platform may expand the target cancer profile to include deep-seated cancers and widespread metastatic cancers.

项与 Pexastimogene devacirepvec 相关的新闻（医药）

2025-07-31

·医药观澜

速递丨李氏大药厂抗PD-L1单抗新适应症获批，治疗小细胞肺癌

7月30日，中国国家药监局（NMPA）官网最新公示，李氏大药厂旗下子公司兆科肿瘤申报的抗PD-L1单克隆抗体索卡佐利单抗新适应症上市申请已获得批准。根据李氏大药厂公开资料可知，该药本次获批的适应症为联合化疗一线治疗广泛期小细胞肺癌。截图来源：NMPA官网索卡佐利单抗是一款全人源PD-L1人免疫球蛋白G1（IgG1）单抗，其保留了完整Fc端，抗体依赖的细胞介导的细胞毒性（ADCC）作用作为次要作用机制，Fc段与免疫细胞如NK细胞结合，促进免疫细胞对肿瘤细胞的直接杀伤作用，有助于增强抗体对肿瘤的抑制作用。该产品最早于2023年12月获NMPA批准上市，用于治疗无论PD-L1是否表达的、既往接受含铂化疗治疗失败的复发或转移性宫颈癌患者。本次是索卡佐利单抗在中国获批的又一项适应症。根据李氏大药厂2024年半年报可知，该项新适应症上市申请是基于索卡佐利单抗与化疗结合用作扩散期小细胞肺癌（ES-SCLC）一线治疗的3期临床试验结果。2025年1月，索卡佐利单抗或安慰剂联合卡铂和依托泊苷一线治疗广泛期小细胞肺癌的随机、双盲、安慰剂对照、多中心的3期临床研究成果全文发表于Nature子刊Signal Transduction and Targeted Therapy。该研究结果表明，相对于安慰剂联合卡铂和依托泊苷，索卡佐利单抗联合卡铂和依托泊苷联合取得了总生存期（OS）获益，达到了试验预设的主要终点，中位OS延长2.32个月，降低患者死亡风险达20.1%。对于年龄＜65岁的男性，延长患者生存期超过4个月之久。小细胞肺癌（SCLC）占肺癌总数的15%-20%，具有恶性程度高、转移早、疾病进展迅速等特点，预后极差。SCLC分为局限期和广泛期，其中约30%-40%的患者确诊时处于局限期，其余处于广泛期。长期以来，以铂类为基础的化疗是SCLC的核心方案，但患者易复发，而“免疫+化疗”联合治疗有望为这类患者带来新的治疗选择。除了已获批的适应症，索卡佐利单抗还在被开发治疗其他癌症类型，包括骨肉瘤，以及结合Pexa-vec（溶瘤病毒）治疗黑色素瘤。参考资料：[1]2025年07月30日药品批准证明文件送达信息[2]李氏大药厂截至二零二四年六月三十日止六个月中期业绩. Retrieved Aug 28 , 2024. From http://www.cninfo.com.cn/new/disclosure/detail?plate=hke&orgId=gshk0008221&stockCode=00950&announcementId=1221025407&announcementTime=2024-08-28%2016:56[3]影响因子40.8！索卡佐利单抗或安慰剂联合卡铂和依托泊苷一线治疗广泛期小细胞肺癌的III期临床研究成果发表国际知名学术期刊！. Retrieved Jan 16 , 2025. From https://mp.weixin.qq.com/s/Oy3VAtxSKaXV_lZEEJzc9Q[4]重磅 | 索卡佐利单抗纳入《中国妇科肿瘤临床实践指南（2024版）》——中国宫颈癌患者福音！. Retrieved Sep 26 , 2024. From https://mp.weixin.qq.com/s/l5CEuSH2ym88xKpmbHSNNw免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

临床3期抗体药物偶联物上市批准临床结果免疫疗法

2024-11-25

·艾美达医药咨询

“以毒攻毒”抗癌的溶瘤病毒药物开发难点如何破解？

目前，全球市面上4款溶瘤病毒产品当中，中国的安科瑞占据一席之地，这预示着我国溶瘤病毒药物开发走在国际前列。然而，已上市的溶瘤病毒产品面临着销售乏力、疗效有待提升、用药途径限制了推广等挑战。溶瘤病毒药物开发过程当中，有哪些困难与挑战？采取哪些策略才能克服呢？目前已上市的4款溶瘤病毒产品一览表 2024年10月26-27日，第二届溶瘤病毒创新与合作大会在武汉召开。大会设置了“溶瘤病毒药物开发策略与挑战”PANEL讨论环节，深圳市华药康明生物药业有限责任公司创始人、董事长袁明担任主持人，与广州威溶特医药科技有限公司董事长颜光美、上海允英生物医药科技有限公司CEO张道允、浙江理工大学生命科学与医药学院教授&杭州功楚生物科技有限公司首席科学家李恭楚、武汉博威德生物技术有限公司董事长兼首席科学家蔡立刚、上海美迪西生物医药股份有限公司首席科学官彭双清等嘉宾同台，从技术层面和监管层面探讨了溶瘤病毒药物开发遇到的痛点和难点，寻求破局之道。袁明：溶瘤病毒发展滞后有哪些因素，溶瘤病毒开发面临的主要挑战是什么？张道允：溶瘤病毒做了100多年了，为什么还没有很惊艳的效果出来？溶瘤病毒属于免疫治疗的一份子，它在整个免疫治疗当中处于什么样的地位，怎么和其他药物联用，才能够达到比较好的效果，这是目前的核心，也是我们所努力的方向。溶瘤病毒治疗实体瘤，联用是一个比较好的选择，到底怎么联用需要大家再探索。颜光美：我们要等待机会，等溶瘤病毒推进到重要的临床阶段。目前滨会生物的OH2做到了三期，其他公司更多是在一期、二期，等我们进入到更后期，或者有更多适应症用溶瘤病毒，可能就会产生惊艳的结果。我们不要忘记免疫治疗PD-1、PD-L1等，在很长一段时间内，没有一个肿瘤学家把它当一回事，一直到它效果显现。溶瘤病毒的优势是安全性好，随着给药方式的改良，随着一些好的结果出现，一定会有引人注目的一天。李恭楚：溶瘤病毒真正应用实践的历史还比较短，我们对溶瘤病毒感染过程中的调控细节尚未完全清楚，比如哪些是正向的调控，哪些是负向的调控?只有我们对病毒知道得越多，才能知道怎样让它更好地应用。蔡立刚：首先，加强教育，包括受众的教育和医生的教育。我们从事溶瘤病毒研究的人，不仅仅是要研究自己的病毒，而且要开展教育活动，就像刘滨磊教授一样，经常举办这样的教育活动。人们普遍认为病毒对人体是有侵害作用的，感染病毒以后要用抗病毒的药物，然而病毒改造后可以用于抗肿瘤、治疗疾病，这需要加强教育、转变观念。其次，优化监管，促进溶瘤病毒行业的发展。比如监管部门对产品的宿主DNA残留含量要求是否要跟疫苗一样的标准，疫苗主要是针对儿童的，它要把表征宿主DNA的残留维持在很低的水平，但对一个肿瘤病人来说稍微增加一点点也无妨。监管要求越严，企业在这个问题上花费的时间越多，一定程度上延缓了研究进程。要提高溶瘤病毒的发展速度，要从各个方面进行改善。彭双清：我们做的是一个裁判官的工作，要评价病毒的安全性和有效性，而且是在临床前。人类跟病毒作斗争有相当长的历史，病毒的危害大家都记忆犹新。利用病毒，它所面临的挑战主要是风险问题，所以临床前基础者要与临床研究者紧密合作。袁明：在当前溶瘤病毒产品的开发中，怎样更好地提高产品的成药性？张道允：我认为要不停地试，各个癌种都要尝试一下。蔡立刚：提高溶瘤病毒产品的成药性，首要因素是要安全性，溶瘤病毒的产品在安全性方面应该没有大的问题；其次是有效性，需要在动物和人身上验证；另外，它的制作过程要可及，即成本要低，如果溶瘤病毒产品生产出来后几十万一针，病人用不起，它的成药性就低，成药性和可使用性有很大的关系。颜光美：一方面是技术层面的东西，需要采取正确的研发的路径，可以借助协作机构的力量，比如彭教授代表的CRO的应用，极大地推动了中国包括溶瘤病毒在内的成药的过程，提高了成药性。另一方面是监管层面，建议监管部门借鉴先进经验，改良监管机制，比如日本的监管既有科学、严谨、细致的一面，也有非常讲道理的一面，如果在IIT当中验证过产品的安全可靠性，正式做临床试验的时候可以沿用相关数据。李恭楚：这涉及溶瘤病毒将来的发展趋势，到底是单药还是联用还不明朗，我觉得联用的可能性更大。溶瘤病毒第一特性是通过复制来裂解，其次才是免疫，将来有可能和谁去联合，随着研究的进展慢慢地会显示出来，它是一个需要积累的过程。彭双清：成药性就是要保证它的安全性、有效性以及质量可控性，而且要满足未被满足的临床需求。与会同期，有关部门也召集了专家研讨包括溶瘤病毒在内的新型治疗产品的发展问题，相信随着监管的改进，成药性会增强。袁明：我也补充一点在成药性的有效性方面，虽然溶瘤病毒是一个广谱治疗实体瘤的方式，因为溶瘤病毒有不同的嗜性，每一种溶瘤病毒有其擅长的适应症。在此基础上要筛选出哪一部分病人适合这种治疗方法，这牵涉到生物标志物的筛选，病人的选择是非常重要的。临床方案上，现有的获批的四个溶瘤病毒产品，在临床方案的应用上存在一定的缺陷，长时间间隔的用药方式有非常大的不合理性，这里面有很大的优化空间。比如JX594治疗癌症的临床效果比Olvi-Vec差，主要是用药方案的不同，JX594用药方案基本上是静脉用药，间隔两周或者三周，而Olvi-Vec是连续5天静脉用药，我认为Olvi-Vec的用药方案远远好于JX594。只有一个更合理的用药方案才能产生最佳的治疗效果，怎么测试、优化出一个更科学、有效的临床方案，才能把你产品的治疗潜力发挥到极致，是临床开发中需要考虑的问题。另外一个是联合用药的问题，溶瘤病毒大概率要联合用药，肿瘤治疗中非常少有单药应用。因为肿瘤是一个复杂性的疾病，有多维度的复杂性，所以想要解决它不能靠单一的方式，那么联合哪些治疗方式，方案设计也非常重要。一个药物产品的成药性主要是安全、有效、可生产，不管你多有效、多安全，如果你这个药的可生产性很差，那这个药在临床上推广或成药性方面有很大的问题，可生产性主要在于质量控制和成本控制。接下来请大家从自身角度出发，分享你们在溶瘤病毒开发中遇到的难点。张道允：困难是一个接着一个克服的，比如像CMC，其实很难做，有一些点控制不下来就是不合格。比如核酸的残留必须控制在10纳克以下，这个是一个硬指标，不管它合理也好、不合理也好，现行的标准就是这样，否则过不去。我们讲产品质量源于设计，有时候监管要求尽管很苛刻，但也得照着去做，往往是在戴着镣铐跳舞。颜光美：我们做的是一个全新的病毒，去申报的时候碰到的困难相对多一些，经验的积累是很重要的。回过头来想，我们在创新的过程中团队的培养和经验的积累是困难的，基本上每前进一步，都是用钱烧出来的，要付出很多的代价。蔡立刚：我们公司做的产品可以说是一个地地道道的原创，柯萨奇病毒B3重组后用于静脉注射，是一个新靶点，用药的途径是新途径，静脉注射相比局部注射/瘤内注射更难获得监管部门批准。从2010年开始，到今年14年了，还在申报临床批件阶段，我们还在坚持，痛并快乐着。第二个痛点，研发需要不断地砸钱，钱从哪里来呢？感谢我的房东、投资人、股东，不断地给钱。我们为溶瘤病毒这个产品的赛道不断地充实而努力，我想肯定会成功的，溶瘤病毒是值得我们付出毕生精力的赛道和产品，值得我们一搏。彭双清：溶瘤病毒这一类型的modality可以说是一个现代科学高度集中的表现，是现代分子生物学的最前沿，通过基因分子修饰，把危害人类的病毒变为人类的宝贝，来拯救人类的身体健康，里面有很多的科学问题尚未解决。它的研发是一个多学科的整合，针对它的监管不能用传统的模式，将来不管是CRO也好，还是研发者也好，目标都是共同一致的，希望形成一种独特的审评机制，这是我们共同努力的一个方向。总之，随着溶瘤病毒药物研发技术的提升及监管的优化，相信未来会有更多的溶瘤病毒产品被研发出来，并应用到肿瘤的临床治疗当中，造福更多的癌症患者。声明：本文由现场对话整理而成，未经嘉宾审核，仅供交流之用，不构成投资建议。 END ------------------------------ 「长按」二维码添加小达「进群」与更多行业伙伴共探市场前沿资讯艾美达医药咨询艾美达（北京）医药信息咨询有限公司，成立于2014年4月，是一家专业的医药行业咨询服务提供商。公司致力于将产业政策研究与真实世界的数据挖掘深度结合，洞悉行业政策对市场的影响，通过专业的研究提供前瞻性的市场分析，为企业产品上市后的市场准入提供整体解决方案。

免疫疗法高管变更临床3期

2024-10-15

·Pharmaceutical Technology

Transgene’s stock drops after Phase II cancer jab trial misses primary endpoint

Transgene’s Phase II trial of viral-based vaccine TG4001 failed to meet its primary endpoint. Credit: Kitsawet Saethao via Shutterstock. Transgene ’s stock has dropped after a Phase II trial of its therapeutic vaccine candidate TG4001 (tipapkinogene sovacivec) failed to meet its primary endpoint of improvement in progression-free survival (PFS) in solid tumours. Transgene’s share price fell 18.8% from €1.17 at close on 11 October to a low of €0.95 on Monday morning (14 October) after the announcement, settling at around €1 per share. The trial (NCT03260023) aimed to assess the impact of TG4001 in combination with Merck KgaA’s Bavencio (avelumab), a PD-L1 checkpoint inhibitor, in 150 patients with recurrent or metastatic HPV16-positive cervical and anogenital cancers who were either treatment-naïve or had one prior systemic chemotherapy, but no earlier immunotherapy. The addition of TG4001 did not produce statistically significant improvements in PFS across the study population, however, Transgene said it remains optimistic. In a subgroup of patients with cervical cancer – comprising about 54% of the trial population – the data suggested a potential trend towards improved PFS. The French biotech is planning further analysis, including examining the data by PD-L1 status, before deciding on the next steps for the candidate’s development. PD-L1 status refers to the level of expression of the PD-L1 protein on tumour cells, which can influence how well a patient’s cancer responds to Bavencio. See Also: Bayer applies for EU approval of menopause drug elinzanetant ENHERTU gains conditional approval in China to treat NSCLC TG4001, a viral-based vaccine, works by inducing an immune response against cells expressing the HPV16 E6 and E7 antigens, aided by the inclusion of human IL-2 to strengthen this immune reaction. In the announcement accompanying the data, Transgene’s CEO Alessandro Riva said: “Failure to meet the primary objective in our Phase II study with TG4001 is disappointing. Nevertheless, we are encouraged by the positive efficacy trend in favour of the combination regimen in cervical cancer patients.” Transgene said that it remains focused on its lead asset TG4050 , an individualised cancer vaccine that is in a Phase I/II trial (NCT04183166) in patients with head and neck cancer. TG4050 is based on Transgene’s myvac platform, which generates personalised therapies, based on patient-specific mutations (neoantigens), that are designed to induce a T cell response to tumour cells. The company expects to share 24-month data on Phase I patients in November at the Society for Immunotherapy of Cancer (SITC) conference. According to a GlobalData report , cancer vaccines are a key immuno-oncology development trend. TG4050 is a personalised vaccine, whereas TG4001 is an off-the-shelf standardised treatment. According to over half of high-prescribing key opinion leaders who responded to a GlobalData survey in 2023, personalised mRNA vaccines are the most promising cancer vaccine type. GlobalData is the parent company of Clinical Trials Arena. The company is also developing an oncolytic virus therapy, BT-001, for treating solid tumours in partnership with BioInvent International . The therapy is being evaluated in a Phase I/IIa clinical trial (NCT04725331) as a single agent and in combination with MSD’s PD-1 checkpoint inhibitor Keytruda (pembrolizumab). Transgene’s journey with oncolytic virus therapies has been challenging. In May 2023, AstraZeneca ended its four-year partnership with the company, a collaboration formed in 2019 with a $10m upfront payment to Transgene to develop oncolytic virus candidates. The partnership’s troubles started early, as one of Transgene’s candidates Pexa-Vec failed a Phase III trial (NCT02562755) just months after the deal was signed.

临床2期疫苗上市批准免疫疗法临床3期

100 项与 Pexastimogene devacirepvec 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10485	Pexastimogene devacirepvec	-	DB15069

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
晚期肝细胞癌	临床3期	美国	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	中国	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	澳大利亚	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	加拿大	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	法国	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	德国	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	中国香港	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	以色列	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	意大利	SillaJen, Inc.	2015-10-01
晚期肝细胞癌	临床3期	新西兰	SillaJen, Inc.	2015-10-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03206073 (Pubmed)	临床1/2期	结直肠癌	34	PexaVec	廠願觸簾廠憲築獵鬱廠(遞範壓憲餘鏇築廠觸齋) = 廠膚鏇醖觸遞顧淵鑰獵獵襯膚夢鏇繭憲繭築糧 (願襯壓窪獵壓夢鏇齋襯 )	-	2023-02-01
NCT02630368 (METROmaJX, Pubmed) 人工标引	临床2期	晚期乳腺癌	10	Cyclophosphamide+Pexastimogene devacirepvec	醖醖淵築糧鹽範顧夢鬱(窪夢築獵窪襯齋鏇鹽積) = 簾淵壓鬱簾觸衊遞築鹽齋齋範鑰壓構窪觸餘餘 (餘製夢遞淵簾繭鹹衊膚, 1.1 ~ 1.9) 更多	积极	2022-12-06
NCT03071094 (CTgov)	临床1/2期	晚期肝细胞癌	14	Nivolumab+Pexa Vec (Pexa-Vec Combined With Nivolumab - Phase I)	鏇鏇鑰簾願築蓋糧壓築 = 齋製獵鑰廠窪齋築獵製願壓觸範廠構窪觸壓淵 (鹹糧積獵簾衊鹹獵鹽蓋, 顧夢窪築繭壓鑰艱獵鬱 ~ 鹹築醖繭築艱選鬱遞繭) 更多	-	2021-11-19
				Nivolumab+Pexa Vec (Pexa-Vec Combined With Nivolumab - Phase IIa)	齋壓餘鹹齋襯築選鑰糧(夢獵襯顧顧艱觸鬱壓獵) = 夢廠襯壓壓糧獵廠衊廠蓋淵醖糧構廠鏇網顧網 (醖範鏇膚築窪蓋壓範製, 鹹築蓋淵願製膚膚鬱鏇 ~ 選製選壓憲願鹽鬱構齋) 更多
NCT03206073 (CTgov)	临床1/2期	大肠腺癌 \| 难治性结直肠癌 \| 难治性癌症	34	Pexa-Vec+Durvalumab (1/Arm A1 Pexa-Vec 3 x 10E^8 Plaque-forming Unit (Pfu) + Durvalumab 1500 mg)	壓構選簾簾鹹淵簾鑰願 = 鏇構選簾糧廠夢鹹築獵鹽衊選製糧鹽顧選觸鏇 (艱壓鏇網繭繭簾蓋顧鹽, 衊醖選構淵簾壓艱淵窪 ~ 繭繭網淵淵鬱繭糧憲築) 更多	-	2021-10-26
				Pexa-Vec+Durvalumab (2/Arm A2 Pexa-Vec 1 x 10E^9 Plaque-forming Unit (Pfu) +Durvalumab 1500 mg)	壓構選簾簾鹹淵簾鑰願 = 築鹽築膚網壓蓋艱簾鹹鹽衊選製糧鹽顧選觸鏇 (艱壓鏇網繭繭簾蓋顧鹽, 構選遞遞齋簾糧製簾夢 ~ 鑰製夢願簾憲窪窪製壓) 更多
NCT01394939 (CTgov)	临床1/2期	难治性结直肠癌	52	JX-594 (Single Agent_ Cohort 1)	選衊淵夢艱鹹鹽簾範鹹 = 艱獵夢製繭鹽蓋鏇壓獵齋積鬱壓鬱獵齋鬱壓鹽 (憲壓襯鏇淵鬱獵壓淵齋, 簾醖餘鏇繭鏇範窪憲餘 ~ 鏇構蓋觸範壓醖糧鑰簾) 更多	-	2021-01-08
				JX-594 (Single Agent_Cohort 2)	選衊淵夢艱鹹鹽簾範鹹 = 齋衊鹹憲糧憲網選鹽餘齋積鬱壓鬱獵齋鬱壓鹽 (憲壓襯鏇淵鬱獵壓淵齋, 鏇蓋鹹醖餘鹽廠夢艱壓 ~ 餘獵膚鏇選鑰夢鑰繭糧) 更多
NCT02562755 (PHOCUS, CTgov)	临床3期	晚期肝细胞癌	459	Pexa Vec+Sorafenib (Pexa-Vec Followed by Sorafenib)	憲觸膚衊壓餘壓築顧夢 = 齋積選範製遞餘構網鹽願廠艱窪餘齋範鬱窪醖 (淵鏇鹹鬱淵積鹽憲築窪, 鏇醖蓋製網願網衊選遞 ~ 鑰願鏇憲齋製築積鹹鏇) 更多	-	2020-12-16
				Sorafenib (Sorafenib)	憲觸膚衊壓餘壓築顧夢 = 構夢範蓋製鬱顧鹽繭襯願廠艱窪餘齋範鬱窪醖 (淵鏇鹹鬱淵積鹽憲築窪, 淵鹹鬱糧鹽鏇築鏇襯築 ~ 餘選糧鬱壓壓願鹽鹽製) 更多
NCT01636284 (FLASH, CTgov)	临床2期	晚期肝细胞癌	16	JX-594 recombinant vaccina GM-CSF	衊鹹範衊獵襯簾鹹遞鬱 = 積鏇憲鏇選網壓觸鑰網淵製鹽鹹糧艱鹽餘鬱範 (膚鏇齋鏇鏇鹽鏇遞鹹構, 襯築艱選範築製觸廠夢 ~ 艱鏇鑰壓壓獵鏇齋醖範) 更多	-	2020-11-24
NCT03294083 (AACR 12020 \| AACR 22020) 人工标引	临床1期	晚期肾细胞癌	17	recombinant vaccinia+Cemiplimab-RWLC (dose-escalation and expansion cohort C)	壓範鑰餘繭廠積鬱築鬱(鬱築構繭衊餘觸衊繭簾) = 12/210 events (5.7%) , which includes fever, flu-like symptom, blood pressure change post infusion and pneumonia, which are mostly transient 選膚膚範獵觸願繭構範 (範餘壓襯範積鏇範齋築 )	积极	2020-08-15
NCT02562755 (PHOCUS, Biospace) 人工标引	临床3期	肝癌	-	Pexa-Vec+Sorafenib Tosylate	窪遞襯選鑰鏇網淵壓蓋(憲襯繭鹹膚鏇遞鏇觸鏇) = Sillajen has informed Transgene of the IDMC’s recommendation to stop enrolment in the study, as the study is unlikely to meet its primary objective by the time of the final analysis. 鑰範觸蓋觸鑰艱鏇構鏇 (壓艱餘製夢鹹餘構繭鹹 ) 更多	不佳	2019-08-02
				Sorafenib Tosylate
NCT01387555 (TRAVERSE, Pubmed \| Oncoimmunology) 人工标引	临床2期	晚期肝细胞癌二线	129	BSC+Pexa-Vec	淵鬱糧範願醖夢築選網(淵窪衊鏇製顧鏇積窪獵) = 壓糧餘蓋鑰鹹鑰築製窪鑰蓋選獵觸願構繭膚壓 (鹽鹹艱鑰淵鹹簾艱繭廠 )	不佳	2019-06-03
				BSC	淵鬱糧範願醖夢築選網(淵窪衊鏇製顧鏇積窪獵) = 艱蓋網廠餘壓網顧遞構鑰蓋選獵觸願構繭膚壓 (鹽鹹艱鑰淵鹹簾艱繭廠 )