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标题: VTP-300 作为单一疗法并与单次给药的低剂量 nivolumab 联合给药 [打印本页]

作者: StephenW    时间: 2022-6-23 16:21     标题: VTP-300 作为单一疗法并与单次给药的低剂量 nivolumab 联合给药

VTP-300 作为单一疗法并与单次给药的低剂量 nivolumab 联合给药,没有与治疗相关的严重不良事件和罕见的短暂性转氨酶。

在一些接受 VTP-300 作为单一疗法或与单次低剂量 nivolumab 在加强剂量联合治疗的患者中,观察到乙型肝炎表面抗原 (HBsAg) 显着、持久地降低。基线 HBsAg 较低的患者下降最为显着。

所有接受 VTP-300 单药治疗或与低剂量纳武单抗联合治疗且 HBsAg 下降大于 0.5 log10 的患者在最后一次测量(最后一次给药后长达 8 个月)之前 HBsAg 持续下降。

在 VTP-300 给药后观察到对所有编码抗原的强烈 T 细胞反应(通过过夜刺激测量),特别是对于显着的 CD8+ T 细胞优势,据我们所知,这是任何其他免疫治疗剂从未实现过的。

英国牛津,2022 年 6 月 22 日 (GLOBE NEWSWIRE) -- Vaccitech plc (NASDAQ: VACC),一家临床阶段的生物制药公司,致力于发现和开发用于治疗和预防传染病、癌症的新型免疫疗法和疫苗和自身免疫性疾病,今天宣布对 HBV002 研究 (NCT04778904) 的安全性和有效性数据的中期分析进行更新,该研究由肝病学和实验学教授 Ellie Barnes 教授在 2022 年 EASL 国际肝病大会TM 上作为海报展示牛津大学医学。

更新的分析数据截止日期为 5 月 9 日,现在包括 39 名至少随访三个月的患者,显示 VTP-300 作为单一疗法或当时与单一低剂量 nivolumab 联合使用加强剂量的安全给药,没有与治疗相关的严重不良事件,两名患者患有轻度、快速消退的转氨酶。

在 VTP-300 单药治疗组中,所有三名基线 HBsAg 低于 50 IU/mL 的患者均观察到 HBsAg 有意义且持久的降低。这三名患者在最后一剂 VTP-300 后两个月分别出现 0.7、0.7 和 1.4 log10 下降。在最后一剂 VTP-300 后五或八个月的最后一次随访中,所有三名患者的这些显着下降都持续存在。

对于在加强剂量时接受 VTP-300 联合单次低剂量 nivolumab 的前 8 名患者,6 个月时 HBsAg 的平均降低超过 1 log10,这种效果持续存在,平均下降在最后一剂 VTP-300 后八个月时为 1.15 log10。这种效果在基线 HBsAg 低于 1,000 IU/mL 的患者中最为显着。该组中的一名患者出现了不可检测的 HBsAg 水平,在最后一剂 VTP-300 后持续了 8 个月。

在接受两剂 MVA-HBV 的患者或接受低剂量 nivolumab 和两剂 VTP-300 的患者中未观察到 ≥1 log10 的降低。这两组在中期分析后停止。

“免疫系统可能是实现持久的 HBsAg 消失的必要组成部分,这可能导致慢性乙型肝炎 (CHB) 患者的功能性治愈,”中国大学医学院名誉临床教授 Henry Chan 博士说香港。 “这一令人兴奋的初步数据支持了 VTP-300 作为一种免疫疗法的潜力,它可以刺激抗原特异性免疫反应,并可能成为功能性治愈方案的关键组成部分。我期待着关注未来的临床和组合发展。” Henry Chan 博士是 Vaccitech 的科学顾问,但没有直接参与 HBV002 研究。

在 VTP-300 给药后,观察到对所有编码抗原(核心蛋白、聚合酶和表面抗原)的强烈 T 细胞反应(通过过夜刺激测量),以显着的 CD8+ T 细胞优势显着。

“在 VTP-300 给药 8 个月后,强大的 T 细胞反应和显着、持久的 HBsAg 降低是显着的,”Vaccitech 首席科学官 Thomas Evans 医学博士说。 “我们相信,我们在起始 HBsAg 水平较低的患者中观察到的显着效果支持与 Arbutus Biopharma 的 siRNA AB-729 的合作研究,其中大多数治疗患者的 HBsAg 已降低到 100 IU/mL 以下。”

HBV002 研究的登记已完成,共有 55 名患者登记。预计在 2022 年底对所有患者在六个月的随访时间点进行更新的中期分析。

计划在多个国家进行一项试验,以观察低剂量 nivolumab 和 VTP-300(NCT05343481)的 MVA 增强成分的额外剂量的时间,第一例患者预计将在 2022 年第三季度给药。
HBsAg 是慢性乙型肝炎病毒 (HBV) 感染的标志。接受当前标准治疗 HBV 治疗的患者中,只有不到 10% 的患者实现了明显的、持续的 HBsAg 降低或消失,这种状态与疾病的功能性治愈相关。慢性 HBV 的症结在于,由于免疫启动不足和/或由于大量 HBV 蛋白表达导致的异常免疫耐受,免疫系统无法清除病毒。许多参与该领域的人认为,将免疫刺激剂与 HBV 蛋白抑制剂结合使用,以潜在地引发 HBV 的功能性治愈是有意义的。

演示详情
海报标题:异源 ChAdOx1-HBV/MVA-HBV 治疗性疫苗 (VTP-300) 作为单一疗法并与低剂量 nivolumab 联合用于使用核苷(酸)类似物的病毒抑制 CHB 患者的 1b/2a 期研究
海报编号:SAT-428
演讲者:牛津大学纳菲尔德医学系肝病学和实验医学教授 Ellie Barnes
摘要:3328

关于HBV002

HBV002 是一项开放标签试验,旨在评估 ChAdOx1-HBV 和 MVA-HBV (VTP-300) 联合或不联合低剂量 nivolumab 在核仁上 HBV DNA 抑制的慢性 HBV 患者中的安全性、免疫原性和初步疗效(t)ide 疗法。

截至 2022 年 6 月 22 日,已有 55 名患者入组,未报告涉及安全性信号或疫苗相关的严重不良事件。

2021 年 11 月在 AASLD The Liver Meeting® 上提交的先前 HBV002 中期分析数据显示,与服用 ChAdOx1 的健康对照相比,VTP-300 诱导了对所有抗原的抗原特异性 T 细胞反应,对核心和聚合酶的反应升高-HBV001 中单独的HBV,对表面抗原表现出更大的反应。与 HBV001 结果一样,在大多数患者中测量了 T 细胞对基因型 D 特异性肽的交叉反应。

关于 VTP-300

VTP-300 是一种新型免疫疗法,以初免-增强方案给药,其中免疫系统用腺病毒 (ChAdOx1) 启动并用痘病毒 (MVA) 增强。两种载体都经过修饰以提高安全性,增强它们诱导的免疫反应,并包括 HBV 特异性抗原,包括核心、聚合酶和表面抗原。迄今为止产生的临床数据表明该方案通常是安全且耐受性良好的,抗原特异性 T 细胞对每种抗原的反应均受到刺激,并且当单独给予或联合给予该方案时,乙型肝炎表面抗原显着减少在加强时使用低剂量的纳武利尤单抗。
作者: StephenW    时间: 2022-6-23 16:23

VTP-300 as a monotherapy and in combination with a single administration of low-dose nivolumab was administered, with no treatment-related serious adverse events and infrequent transient transaminitis.

Meaningful, durable reductions of Hepatitis B surface antigen (HBsAg) were seen in some patients who received VTP-300 as either a monotherapy or in combination with a single low dose of nivolumab at the booster dose. Declines were most prominent in patients with lower baseline HBsAg.

All patients who received VTP-300 monotherapy or in combination with low-dose nivolumab and who had a HBsAg decline greater than 0.5 log10 had durable reductions of HBsAg until the last measurement (up to eight months after last dose).

A robust T cell response against all encoded antigens, measured by overnight stimulation, was observed following VTP-300 administration, notably for marked CD8+ T cell predominance, which, to our knowledge, has never been achieved by any other immunotherapeutic.

OXFORD, United Kingdom, June 22, 2022 (GLOBE NEWSWIRE) -- Vaccitech plc (NASDAQ: VACC), a clinical-stage biopharmaceutical company engaged in the discovery and development of novel immunotherapeutics and vaccines for the treatment and prevention of infectious diseases, cancer, and autoimmune diseases, today announced an update to the interim analysis of safety and efficacy data from the HBV002 study (NCT04778904), which is being presented as a poster at the 2022 EASL International Liver CongressTM by Professor Ellie Barnes, Professor of Hepatology and Experimental Medicine at the University of Oxford.

The updated analysis, with a data cut-off of May 9th, which now includes 39 patients with at least three months of follow-up, shows that VTP-300 as a monotherapy or in combination with a single low-dose nivolumab at the time of the booster dose was safely administered with no treatment-related serious adverse events and two patients with mild, rapidly resolving transaminitis.

In the VTP-300 monotherapy group, meaningful and durable reductions of HBsAg were seen in all three patients with baseline HBsAg under 50 IU/mL. These three patients had 0.7, 0.7 and 1.4 log10 declines two months after the last dose of VTP-300. These dramatic declines have persisted in all three patients at their latest follow-up at five or eight months after the last dose of VTP-300.

For the first eight patients who received VTP-300 in combination with a single low-dose of nivolumab at the time of the booster dose, the mean reduction in HBsAg was over 1 log10 at six months, an effect that persisted, with a mean decline of 1.15 log10 at eight months after the last dose of VTP-300. The effect was most prominent in patients with baseline HBsAg lower than 1,000 IU/mL.   One patient in this group developed a non-detectable HBsAg level, which continued eight months after the last dose of VTP-300.

No reductions ≥1 log10 were seen in patients who received two doses of MVA-HBV, or in patients who received low-dose nivolumab with both doses of VTP-300. These two groups were discontinued after interim analysis.

“The immune system is likely a needed component in achieving durable HBsAg loss that could lead to a functional cure for patients with chronic hepatitis B (CHB),” said Dr. Henry Chan, Honorary Clinical Professor, Faculty of Medicine, The Chinese University of Hong Kong. “This exciting initial data supports VTP-300’s potential as an immunotherapy that can stimulate an antigen-specific immune response and could be a critical component of a functional cure regimen. I look forward to following future clinical and combination developments.” Dr. Henry Chan is a scientific advisor to Vaccitech but not directly involved in the HBV002 study.

A robust T cell response against all encoded antigens (core protein, polymerase and surface antigen), measured by overnight stimulation, was observed following VTP-300 administration, notable for marked CD8+ T cell predominance.

“The robust T cell response and marked, durable HBsAg reduction eight months after VTP-300 administration is remarkable,” said Thomas Evans, M.D., Chief Scientific Officer of Vaccitech. “We believe the prominent effect we are observing in patients with lower starting HBsAg levels supports the collaborative study with Arbutus Biopharma’s siRNA, AB-729, in which HBsAg has shown to be lowered below 100 IU/mL in a majority of treated patients.”

Enrollment in the HBV002 study is complete with 55 patients enrolled. An updated interim analysis for all patients at the six month follow-up timepoint is expected at the end of 2022.

A trial to look at timing of low dose nivolumab and additional doses of the MVA boost component of VTP-300 (NCT05343481) is planned in multiple countries, with the first patient expected to be dosed in the third quarter of 2022.
HBsAg is a hallmark of chronic hepatitis B virus (HBV) infection. Fewer than 10% of patients on current standard of care HBV therapies ever achieve distinct, sustained HBsAg decrease or loss, a state associated with functional cure of the disease.   The crux of chronic HBV is the immune system’s inability to clear the virus due to insufficient immune priming and/or aberrant immune tolerance due to large quantities of HBV protein expression. Many involved in the field believe it makes sense to combine an immune-stimulating agent with an HBV protein-suppressing agent, to potentially elicit a functional cure to HBV.

Presentation details
Poster Title: Phase 1b/2a study of heterologous ChAdOx1-HBV/MVA-HBV therapeutic vaccination (VTP-300) as monotherapy and combined with low-dose nivolumab in virally-suppressed patients with CHB on nucleos(t)ide analogues
Poster Number: SAT-428
Presenter: Ellie Barnes, Professor of Hepatology and Experimental Medicine, Nuffield Department of Medicine, University of Oxford
Abstract: 3328

About HBV002

HBV002 is an open-label trial designed to evaluate the safety, immunogenicity and preliminary efficacy of ChAdOx1-HBV and MVA-HBV (VTP-300), with or without low-dose nivolumab, in patients with chronic HBV with suppressed HBV DNA on nucleos(t)ide therapy.

As of June 22, 2022, 55 patients have been enrolled, and no concerning safety signals or vaccine-related serious adverse events have been reported.

Data from a previous interim analysis of HBV002 presented at the AASLD The Liver Meeting® in November 2021 showed that VTP-300 induced antigen specific T cell responses to all antigens, with elevated responses to core and polymerase, as compared to healthy controls dosed with ChAdOx1-HBV alone in HBV001, who exhibited a greater response to surface antigen. As in the HBV001 results, T cell responses cross-reactive to Genotype D-specific peptides were measured in the majority of patients.

About VTP-300

VTP-300 is a novel immunotherapy, dosed in a prime-boost regimen, whereby the immune system is primed with an adenovirus (ChAdOx1) and boosted with a pox virus (MVA). Both vectors have been modified to improve safety, enhance the immune response they induce and include HBV specific antigens including core, polymerase and surface antigen. Clinical data generated to date has demonstrated this regimen to be generally safe and well-tolerated, that antigen specific T cell responses are stimulated to each antigen and there were meaningful reductions in hepatitis B surface antigen when this regimen is given alone or when given in combination with a low dose of nivolumab at the boost.
作者: windu    时间: 2022-6-24 07:45

终极组合,729+vtp+单抗+派
作者: 乙肝人1949    时间: 2022-6-24 09:12

假装很期待
作者: windu    时间: 2022-6-24 09:35

顺其自然,有就干,没有难道就不工作了
作者: 乙肝人1949    时间: 2022-6-24 09:57

假装,十分自然看这个文章




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