当前位置：
X-MOL 学术
›
Br. J. Cancer
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Clinical activity of a htert (vx-001) cancer vaccine as post-chemotherapy maintenance immunotherapy in patients with stage IV non-small cell lung cancer: final results of a randomised phase 2 clinical trial.
British Journal of Cancer ( IF 6.4 ) Pub Date : 2020-03-25 , DOI: 10.1038/s41416-020-0785-y Cesare Gridelli 1 , Tudor Ciuleanu 2 , Manuel Domine 3 , Aleksandra Szczesna 4 , Isabel Bover 5 , Manuel Cobo 6 , Nikolaos Kentepozidis 7 , Konstantinos Zarogoulidis 8 , Charalabos Kalofonos 9 , Andrzej Kazarnowisz 10 , Magdalena Korozan 11 , Ramon de Las Penas 12 , Margarita Majem 13 , Antonio Chella 14 , Frank Griesinger 15 , Evangelos Bournakis 16 , Parvis Sadjadian 17 , Athanasios Kotsakis 18 , Thierry Chinet 19 , Kostantinos N Syrigos 20 , Pierpaolo Correale 21 , Catherine Gallou 22 , Jeanne- Menez Jamet 22 , Eleni- Kyriaki Vetsika 23 , Kostas Kosmatopoulos 22 , Vassilis Georgoulias 23 ,
British Journal of Cancer ( IF 6.4 ) Pub Date : 2020-03-25 , DOI: 10.1038/s41416-020-0785-y Cesare Gridelli 1 , Tudor Ciuleanu 2 , Manuel Domine 3 , Aleksandra Szczesna 4 , Isabel Bover 5 , Manuel Cobo 6 , Nikolaos Kentepozidis 7 , Konstantinos Zarogoulidis 8 , Charalabos Kalofonos 9 , Andrzej Kazarnowisz 10 , Magdalena Korozan 11 , Ramon de Las Penas 12 , Margarita Majem 13 , Antonio Chella 14 , Frank Griesinger 15 , Evangelos Bournakis 16 , Parvis Sadjadian 17 , Athanasios Kotsakis 18 , Thierry Chinet 19 , Kostantinos N Syrigos 20 , Pierpaolo Correale 21 , Catherine Gallou 22 , Jeanne- Menez Jamet 22 , Eleni- Kyriaki Vetsika 23 , Kostas Kosmatopoulos 22 , Vassilis Georgoulias 23 ,
Affiliation
|
BACKGROUND
The cancer vaccine Vx-001, which targets the universal tumour antigen TElomerase Reverse Transcriptase (TERT), can mount specific Vx-001/TERT572 CD8 + cytotoxic T cells; this immune response is associated with improved overall survival (OS) in patients with advanced/metastatic non-small cell lung cancer (NSCLC).
METHODS
A randomised, double blind, phase 2b trial, in HLA-A*201-positive patients with metastatic, TERT-expressing NSCLC, who did not progress after first-line platinum-based chemotherapy were randomised to receive either Vx-001 or placebo. The primary endpoint of the trial was OS.
RESULTS
Two hundred and twenty-one patients were randomised and 190 (101 and 89 patients in the placebo and the Vx-001 arm, respectively) were analysed for efficacy. There was not treatment-related toxicity >grade 2. The study did not meet its primary endpoint (median OS 11.3 and 14.3 months for the placebo and the Vx-001, respectively; p = 0.86) whereas the median Time to Treatment Failure (TTF) was 3.5 and 3.6 months, respectively. Disease control for >6months was observed in 30 (33.7%) and 26 (25.7%) patients treated with Vx-001 and placebo, respectively. There was no documented objective CR or PR. Long lasting TERT-specific immune response was observed in 29.2% of vaccinated patients who experienced a significantly longer OS compared to non-responders (21.3 and 13.4 months, respectively; p = 0.004).
CONCLUSION
Vx-001 could induce specific CD8+ immune response but failed to meet its primary endpoint. Subsequent studies have to be focused on the identification and treatment of subgroups of patients able to mount an effective immunological response to Vx-001.
CLINICAL TRIAL REGISTRATION
NCT01935154.
中文翻译：
htert（vx-001）癌症疫苗作为IV期非小细胞肺癌患者化疗后维持免疫治疗的临床活性：随机2期临床试验的最终结果。
背景技术靶向通用肿瘤抗原端粒酶逆转录酶（TERT）的癌症疫苗Vx-001可以安装特异性Vx-001 / TERT572 CD8 +细胞毒性T细胞。这种免疫反应与晚期/转移性非小细胞肺癌（NSCLC）患者的总体生存期（OS）改善有关。方法一项随机，双盲，2b期临床试验，在HLA-A * 201阳性，表达TERT表达的转移性NSCLC的一线化疗后未进展的患者中随机接受Vx-001或安慰剂治疗。该试验的主要终点是OS。结果221例患者被随机分组，对190例（安慰剂组和Vx-001组分别为101例和89例）进行了疗效分析。> 2级没有与治疗有关的毒性。该研究未达到其主要终点（安慰剂和Vx-001的中位OS分别为11.3和14.3个月； p = 0.86），而治疗失败的中位时间（TTF）分别为3.5和3.6个月。在分别接受Vx-001和安慰剂治疗的30例患者中（33.7％）和26例患者（25.7％）病情控制超过6个月。没有记录的客观CR或PR。与无反应者相比，接受OS显着延长的29.2％的疫苗接种患者中观察到了持久的TERT特异性免疫反应（分别为21.3和13.4个月； p = 0.004）。结论Vx-001可以诱导特异性CD8 +免疫反应，但未能达到其主要终点。随后的研究必须集中在能够对Vx-001产生有效免疫应答的患者亚组的鉴定和治疗上。临床试验注册NCT01935154。
更新日期：2020-04-24
中文翻译：
htert（vx-001）癌症疫苗作为IV期非小细胞肺癌患者化疗后维持免疫治疗的临床活性：随机2期临床试验的最终结果。
背景技术靶向通用肿瘤抗原端粒酶逆转录酶（TERT）的癌症疫苗Vx-001可以安装特异性Vx-001 / TERT572 CD8 +细胞毒性T细胞。这种免疫反应与晚期/转移性非小细胞肺癌（NSCLC）患者的总体生存期（OS）改善有关。方法一项随机，双盲，2b期临床试验，在HLA-A * 201阳性，表达TERT表达的转移性NSCLC的一线化疗后未进展的患者中随机接受Vx-001或安慰剂治疗。该试验的主要终点是OS。结果221例患者被随机分组，对190例（安慰剂组和Vx-001组分别为101例和89例）进行了疗效分析。> 2级没有与治疗有关的毒性。该研究未达到其主要终点（安慰剂和Vx-001的中位OS分别为11.3和14.3个月； p = 0.86），而治疗失败的中位时间（TTF）分别为3.5和3.6个月。在分别接受Vx-001和安慰剂治疗的30例患者中（33.7％）和26例患者（25.7％）病情控制超过6个月。没有记录的客观CR或PR。与无反应者相比，接受OS显着延长的29.2％的疫苗接种患者中观察到了持久的TERT特异性免疫反应（分别为21.3和13.4个月； p = 0.004）。结论Vx-001可以诱导特异性CD8 +免疫反应，但未能达到其主要终点。随后的研究必须集中在能够对Vx-001产生有效免疫应答的患者亚组的鉴定和治疗上。临床试验注册NCT01935154。
京公网安备 11010802027423号