Three-year Phase 1 Follow-Up Data for MRNA-based Individualized Immunotherapy Candidate Show Persistence of Immune Response and Delayed Tumor Recurrence in Some Patients With Resected Pancreatic Cancer
Three-year Phase 1 Follow-Up Data for MRNA-based Individualized Immunotherapy Candidate Show Persistence of Immune Response and Delayed Tumor Recurrence in Some Patients With Resected Pancreatic Cancer
Three-year follow-up data of an investigator-initiated Phase 1 trial of the individualized mRNA cancer vaccine candidate autogene cevumeran (BNT122, RO7198457) continue to show polyspecific T cell responses up to three years and delayed tumor recurrence in patients with resected pancreatic ductal adenocarcinoma ("PDAC")
A randomized Phase 2 clinical trial with autogene cevumeran in patients with resected PDAC is currently enrolling patients at clinical trial sites in the United States, with additional sites planned to open globally
The medical need in PDAC is high with a 5-year overall survival rate of only 8-10%1,2, high recurrence rates after surgery at nearly 80%3 and limited treatment options
Autogene cevumeran, jointly developed by BioNTech and Genentech Inc. ("Genentech"), a member of the Roche Group, is the lead candidate of BioNTech's mRNA-based individualized cancer vaccine platform iNeST and currently being evaluated in three ongoing randomized Phase 2 clinical trials in adjuvant PDAC, first-line melanoma, and adjuvant colorectal cancer
研究人员发起的针对个体化mRNA癌症疫苗候选药自体基因cevumeran（BNT122、RO7198457）的1期临床试验的三年随访数据继续显示多特异性T细胞反应长达三年，切除的胰腺导管腺癌（“PDAC”）患者肿瘤复发延迟
一项针对切除的PDAC患者的自体基因cevumeran的随机2期临床试验目前正在美国的临床试验地点招收患者，并计划在全球开设更多研究点
PDAC的医疗需求很高，5年总存活率仅为8-10％ 1,2，手术后复发率很高，接近80％3，而且治疗选择有限
Autogene cevumeran由BioNTech和罗氏集团旗下的基因泰克公司（“基因泰克”）共同开发，是BioNTech基于mRNA的个体化癌症疫苗平台iNEST的主要候选药物，目前正在进行的三项正在进行的辅助PDAC、一线黑色素瘤和辅助性结直肠癌的随机2期临床试验中进行评估
MAINZ, Germany, April 7, 2024 - BioNTech SE (Nasdaq: BNTX, "BioNTech" or "the Company") today announced three-year follow-up data from a Phase 1 trial with the mRNA-based individualized neoantigen-specific immunotherapy ("iNeST") candidate autogene cevumeran (also known as BNT122, RO7198457) in patients with resected pancreatic ductal adenocarcinoma ("PDAC"). The data show that in 8 out of 16 patients autogene cevumeran elicited an immune response up to three years post administration measured by activated T cells. The persistence of T cels was associated with a longer median recurrence-free survival in cancer vaccine responders.
德国美因茨，2024年4月7日——BioNTech SE（纳斯达克股票代码：BNTX，“BioNTech” 或 “公司”）今天公布了一项针对切除的胰腺导管腺癌（“PDAC”）患者的基于mRNA的个性化新抗原特异性免疫疗法（“iNest”）候选自体基因cevumeran（也称为 BNT122、RO7198457）的1期试验的三年随访数据”）。数据显示，在16名患者中，有8名自身基因cevumeran在给药后三年内产生免疫反应，由活化的T细胞测量。T细胞的持续存在与癌症疫苗反应者的无复发存活率中位数更长有关。
"These new data are an early signal for the potential of our individualized mRNA cancer vaccine approach in this indication with an unmet medical need. The results indicate that our uridine mRNA-LPX technology can promote activation of cytotoxic T cells that may help to eliminate residual tumor foci at early stages of the disease to delay or prevent recurrence," said Prof. Özlem Türeci, M.D., Co-Founder and Chief Medical Officer at BioNTech. "Our ongoing Phase 2 trial with Genentech aims to confirm these findings on benefit for patients with PDAC compared with the current standard of care treatment in the post-surgical, adjuvant setting in a larger patient population. We remain committed to our vision of personalized cancer medicine and aim to help advance the standard of care for many patients."
“这些新数据是一个早期信号，表明我们在该适应症中采用个性化mRNA癌症疫苗方法的潜力，但医疗需求尚未得到满足。结果表明，我们的尿苷mRNA-LPX技术可以促进细胞毒性T细胞的激活，这可能有助于在疾病的早期阶段消除残留的肿瘤病灶，从而延缓或预防复发。” BioNTech联合创始人兼首席医学官奥兹勒姆·图雷西教授说。“我们正在进行的与基因泰克的2期试验旨在证实这些发现，与目前在更多患者群体中的术后辅助治疗标准相比，PDAC患者获益良多。我们仍然致力于实现个性化癌症药物的愿景，旨在帮助提高许多患者的护理标准。”
The results featured in an oral presentation at the American Association for Cancer Research ("AACR") Annual Meeting 2024 show the following:
美国癌症研究协会（“AACR”）2024年年会的口头报告显示了以下结果：
In 8 of 16 patients, autogene cevumeran elicited high-magnitude T cells specific to the encoded neoantigens.
98% of the T cells targeting individual neoantigens on the tumor and induced by autogene cevumeran were de novo in that they were not detected in blood, tumors, and adjacent tissues prior to administration of the investigational treatment.
Over 80% of the vaccine-induced neoantigen-specific T cells could still be detected up to three years post administration in patients with an immune response. These patients showed a prolonged median recurrence-free survival compared to non-responders.
6 of 8 patients with an immune response to autogene cevumeran remained disease free during the three-year follow-up period, while 7 of the 8 patients without an immune response to the treatment during the trial showed tumor recurrence.
在16名患者中的8例中，自体基因cevumeran激发了编码的新抗原特异的高量度T细胞。
在靶向肿瘤上单个新抗原并由自身基因cevumeran诱导的T细胞中，有98％是从头开始的，因为在进行研究性治疗之前，没有在血液、肿瘤和邻近组织中检测到它们。
在免疫反应患者中，疫苗诱导的新抗原特异性T细胞中有80％以上仍可以在给药后三年内检测到。与无反应者相比，这些患者的无复发存活率中位数更长。
在对自身基因cevumeran有免疫反应的8名患者中，有6名在三年的随访期内保持无病状态，而在试验期间对治疗没有免疫反应的8名患者中，有7名显示肿瘤复发。
The investigator-initiated, single center Phase 1 trial (NCT04161755) evaluated the safety of autogene cevumeran in sequential combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and standard-of-care chemotherapy in 16 patients with resected PDAC. Data from the 1.5-year median follow-up were published in Nature in May 2023. The current data update includes a three-year median follow-up and was presented in a late-breaking oral presentation at the AACR Annual Meeting 2024 in San Diego, California, by principal investigator Vinod Balachandran, M.D., surgeon-scientist at Memorial Sloan Kettering Cancer Center and principal investigator of the study.
这项由研究者发起的单中心1期试验（NCT04161755）评估了自体cevumeran与抗PD-L1免疫检查点抑制剂阿替珠单抗和标准治疗化疗对16例PDAC切除患者进行序列联合治疗的安全性。来自1.5年中位随访的数据于2023年5月发表在《自然》杂志上。当前的数据更新包括为期三年的中位数随访，由首席研究员、纪念斯隆·凯特琳癌症中心的外科科学家、该研究的首席研究员维诺德·巴拉尚德兰医学博士在加利福尼亚州圣地亚哥举行的2024年AACR年会上作了最新口头陈述。
An ongoing open-label, multicenter, randomized Phase 2 trial (NCT05968326), sponsored by Genentech in collaboration with BioNTech, was started in October 2023. The trial will investigate the efficacy and safety of adjuvant autogene cevumeran in combination with the anti-PD-L1 immune checkpoint inhibitor atezolizumab and chemotherapy compared with the current standard of care chemotherapy (mFOLFIRINOX) in patients with PDAC. The Phase 2 trial is currently enrolling patients at clinical trial sites in the United States, with additional sites planned to open globally. Autogene cevumeran is being jointly developed by BioNTech and Genentech and is currently being evaluated in three ongoing randomized Phase 2 clinical trials in adjuvant PDAC (as mentioned above), first-line melanoma, and adjuvant colorectal cancer.
正在进行的开放标签、多中心、随机2期试验（NCT05968326）由基因泰克与BioNTech合作赞助，于2023年10月启动。该试验将研究辅助自体基因头孢美兰联合抗PD-L1免疫检查点抑制剂阿替珠单抗和化疗与当前标准护理化疗（mfolfirinox）对PDAC患者的疗效和安全性。2期试验目前正在美国的临床试验中心招收患者，并计划在全球开设更多研究所。Autogene cevumeran由BioNTech和Genentech共同开发，目前正在进行三项正在进行的辅助PDAC（如上所述）、一线黑色素瘤和辅助性结直肠癌的随机2期临床试验中进行评估。
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About resected pancreatic ductal adenocarcinoma (PDAC)
PDAC is amongst the leading causes of cancer-related deaths in the United States4 with approximately 90% of patients dying within two years of their diagnosis5. A combination of surgical removal and systemic cytotoxic chemotherapy has shown to improve clinical outcomes; however, even with surgical resection, the relapse rate remains high, and the 5-year overall survival is only approximately 20%6 in patients who undergo surgery followed by adjuvant chemotherapy ("ACT") and only 8-10%i,ii in those who do not receive ACT. Thus, there is an unmet medical need for novel therapies for patients with resected PDAC.
关于切除的胰腺导管腺癌（PDAC）
PDAC是美国癌症相关死亡的主要原因之一4，大约90％的患者在诊断后的两年内死亡5。事实证明，手术切除和全身性细胞毒性化疗相结合可以改善临床结果；但是，即使进行手术切除，复发率仍然很高，在接受手术后接受辅助化疗（“ACT”）的患者中，5年的总存活率仅为20％6％，未接受ACT的患者仅为8-10％ i，ii。因此，PDAC切除患者对新疗法的医学需求尚未得到满足。
About iNeST (individualized Neoantigen Specificimmuno Therapy)
iNeST immunotherapies are investigational individualized cancer therapies tailored to a specific patient's tumor. They contain unmodified, pharmacologically optimized mRNA encoding up to 20 patient-specific neoantigens, identified using real-time next-generation sequencing and bioinformatic neoantigen discovery. Neoantigens are proteins that are produced by cancer cells that differ from the proteins produced by healthy cells and are recognized by immune cells. The mRNA is encapsulated in BioNTech's proprietary intravenous RNA-lipoplex delivery formulation which is designed to enhance stability as well as enable targeted delivery to dendritic cells. By analyzing each patient's tumor, BioNTech is able to identify the cancer mutations that may act as neoantigens. Each individual cancer vaccine encodes for neoantigen candidates with the highest likelihood of helping the immune system recognize the cancer. For this purpose, BioNTech has developed an on-demand manufacturing process, following Good Manufacturing Practice (GMP) conditions. Autogene cevumeran is currently being evaluated in various solid tumor indications, including three Phase 2 clinical trials in first-line melanoma, adjuvant colorectal cancer, and adjuvant pancreatic ductal adenocarcinoma.
关于 iNEST（个性化新抗原特异性免疫疗法）
iNEST 免疫疗法是针对特定患者肿瘤量身定制的研究性个体化癌症疗法。它们含有未修改、经过药理学优化的mRNA，可编码多达20种患者特异性新抗原，通过实时下一代测序和生物信息学新抗原发现进行鉴定。新抗原是由癌细胞产生的蛋白质，不同于健康细胞产生的蛋白质，可被免疫细胞识别。该mRNA封装在BioNTech专有的静脉注射RNA-LipoPlex递送配方中，该配方旨在增强稳定性并实现对树突状细胞的靶向输送。通过分析每位患者的肿瘤，BioNTech 能够识别可能起到新抗原作用的癌症突变。每种癌症疫苗都编码新抗原候选药物，帮助免疫系统识别癌症的可能性最大。为此，BioNTech根据良好生产规范（GMP）条件开发了按需制造工艺。Autogene cevumeran目前正在评估各种实体瘤适应症，包括针对一线黑色素瘤、辅助性结直肠癌和辅助胰腺导管腺癌的三项2期临床试验。