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
研究人員發起的針對個體化mRNA癌症疫苗候選藥自體基因cevumeran（BNT122、RO7198457）的1期臨床試驗的三年隨訪數據繼續顯示多特異性T細胞反應長達三年，切除的胰腺導管腺癌（“PDAC”）患者腫瘤復發延遲
一項針對切除的PDAC患者的自體基因cevumeran的隨機2期臨床試驗目前正在美國的臨床試驗地點招收患者，並計劃在全球開設更多研究點
PDAC的醫療需求很高，5年總存活率僅爲8-10％ 1,2，手術後複發率很高，接近80％3，而且治療選擇有限
Autogene cevumeran由BioNTech和羅氏集團旗下的基因泰克公司（“基因泰克”）共同開發，是BioNTech基於mRNA的個體化癌症疫苗平台iNEST的主要候選藥物，目前正在進行的三項正在進行的輔助PDAC、一線黑色素瘤和輔助性結直腸癌的隨機2期臨床試驗中進行評估
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.
德國美因茨，2024年4月7日——BioNTech SE（納斯達克股票代碼：BNTX，“BioNTech” 或 “公司”）今天公佈了一項針對切除的胰腺導管腺癌（“PDAC”）患者的基於mRNA的個性化新抗原特異性免疫療法（“iNest”）候選自體基因cevumeran（也稱爲 BNT122、RO7198457）的1期試驗的三年隨訪數據”）。數據顯示，在16名患者中，有8名自身基因cevumeran在給藥後三年內產生免疫反應，由活化的T細胞測量。T細胞的持續存在與癌症疫苗反應者的無復發存活率中位數更長有關。
"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."
“這些新數據是一個早期信號，表明我們在該適應症中採用個性化mRNA癌症疫苗方法的潛力，但醫療需求尚未得到滿足。結果表明，我們的尿苷mRNA-LPX技術可以促進細胞毒性T細胞的激活，這可能有助於在疾病的早期階段消除殘留的腫瘤病竈，從而延緩或預防復發。” BioNTech聯合創始人兼首席醫學官奧茲勒姆·圖雷西教授說。“我們正在進行的與基因泰克的2期試驗旨在證實這些發現，與目前在更多患者群體中的術後輔助治療標準相比，PDAC患者獲益良多。我們仍然致力於實現個性化癌症藥物的願景，旨在幫助提高許多患者的護理標準。”
The results featured in an oral presentation at the American Association for Cancer Research ("AACR") Annual Meeting 2024 show the following:
美國癌症研究協會（“AACR”）2024年年會的口頭報告顯示了以下結果：
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，自體基因cevumeran激發了編碼的新抗原特異的高量度T細胞。
在靶向腫瘤上單個新抗原並由自身基因cevumeran誘導的T細胞中，有98％是從頭開始的，因爲在進行研究性治療之前，沒有在血液、腫瘤和鄰近組織中檢測到它們。
在免疫反應患者中，疫苗誘導的新抗原特異性T細胞中有80％以上仍可以在給藥後三年內檢測到。與無反應者相比，這些患者的無復發存活率中位數更長。
在對自身基因cevumeran有免疫反應的8名患者中，有6名在三年的隨訪期內保持無病狀態，而在試驗期間對治療沒有免疫反應的8名患者中，有7名顯示腫瘤復發。
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.
這項由研究者發起的單中心1期試驗（NCT04161755）評估了自體cevumeran與抗PD-L1免疫檢查點抑制劑阿替珠單抗和標準治療化療對16例PDAC切除患者進行序列聯合治療的安全性。來自1.5年中位隨訪的數據於2023年5月發表在《自然》雜誌上。當前的數據更新包括爲期三年的中位數隨訪，由首席研究員、紀念斯隆·凱特琳癌症中心的外科科學家、該研究的首席研究員維諾德·巴拉尚德蘭醫學博士在加利福尼亞州聖地亞哥舉行的2024年AACR年會上作了最新口頭陳述。
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.
正在進行的開放標籤、多中心、隨機2期試驗（NCT05968326）由基因泰克與BioNTech合作贊助，於2023年10月啓動。該試驗將研究輔助自體基因頭孢美蘭聯合抗PD-L1免疫檢查點抑制劑阿替珠單抗和化療與當前標準護理化療（mfolfirinox）對PDAC患者的療效和安全性。2期試驗目前正在美國的臨床試驗中心招收患者，並計劃在全球開設更多研究所。Autogene cevumeran由BioNTech和Genentech共同開發，目前正在進行三項正在進行的輔助PDAC（如上所述）、一線黑色素瘤和輔助性結直腸癌的隨機2期臨床試驗中進行評估。
-----
-----
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.
關於切除的胰腺導管腺癌（PDAC）
PDAC是美國癌症相關死亡的主要原因之一4，大約90％的患者在診斷後的兩年內死亡5。事實證明，手術切除和全身性細胞毒性化療相結合可以改善臨床結果；但是，即使進行手術切除，複發率仍然很高，在接受手術後接受輔助化療（“ACT”）的患者中，5年的總存活率僅爲20％6％，未接受ACT的患者僅爲8-10％ i，ii。因此，PDAC切除患者對新療法的醫學需求尚未得到滿足。
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.
關於 iNEST（個性化新抗原特異性免疫療法）
iNEST 免疫療法是針對特定患者腫瘤量身定製的研究性個體化癌症療法。它們含有未修改、經過藥理學優化的mRNA，可編碼多達20種患者特異性新抗原，通過實時下一代測序和生物信息學新抗原發現進行鑑定。新抗原是由癌細胞產生的蛋白質，不同於健康細胞產生的蛋白質，可被免疫細胞識別。該mRNA封裝在BioNTech專有的靜脈注射RNA-LipoPlex遞送配方中，該配方旨在增強穩定性並實現對樹突狀細胞的靶向輸送。通過分析每位患者的腫瘤，BioNTech 能夠識別可能起到新抗原作用的癌症突變。每種癌症疫苗都編碼新抗原候選藥物，幫助免疫系統識別癌症的可能性最大。爲此，BioNTech根據良好生產規範（GMP）條件開發了按需製造工藝。Autogene cevumeran目前正在評估各種實體瘤適應症，包括針對一線黑色素瘤、輔助性結直腸癌和輔助胰腺導管腺癌的三項2期臨床試驗。
譯文內容由第三人軟體翻譯。