A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial With Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects With High Risk Myeloid and Lymphoid Neoplasms

This is a multicentre, non-randomized, open-label, Phase I/II clinical trial of MDG1011, an investigational medicinal product (IMP), consisting of patient-derived autologous T cells, persistently transduced with a Preferentially Expressed Antigen in Melanoma (PRAME)-specific human leukocyte antigen (HLA)-A*02:01-restricted T cell receptor (TCR).

开始日期2018-03-27

申办/合作机构

MediGene AG

EUCTR2017-000440-18-DE / Not yet recruiting临床1/2期

A Phase I/II, Open-Label, Non-Randomized, Multicentre, Dose-Escalation Clinical Trial with Control Group to Evaluate the Safety, Feasibility and Preliminary Efficacy of PRAME TCR Modified T Cells, MDG1011, in Subjects with High Risk Myeloid and Lymphoid Neoplasms - A Phase I/II clinical trial for TCR modified T cells, MDG1011, in HR myeloid and lymphatic neoplasms

开始日期2017-12-19

申办/合作机构

MediGene AG

100 项与 MDG-1011 相关的临床结果

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100 项与 MDG-1011 相关的转化医学

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100 项与 MDG-1011 相关的专利（医药）

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项与 MDG-1011 相关的新闻（医药）

2023-04-30

·药明康德

治疗阿尔茨海默病的RNAi疗法表现亮眼、第四代EGFR-TKI进入临床... | 一周盘点

▎药明康德内容团队编辑本期看点1. 用于治疗癫痫的再生细胞疗法NRTX-1001疗效亮眼，一次给药后两名患者的癫痫发作活动持续减少，减少超过90%。2. 治疗阿尔茨海默病和脑淀粉样血管病的RNAi疗法ALN-APP获得首个人体试验的积极结果，最高剂量下关键生物标志物的降低幅度可达90%。3. 第四代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）进入临床，对第三代EGFR-TKI治疗后出现的EGFR C797S突变同样具有活性和疗效。药明康德内容团队整理NRTX-1001：公布1/2期临床试验的新数据Neurona Therapeutics公司公布了其候选再生细胞疗法NRTX-1001的1/2期临床试验的初步数据。NRTX-1001是一种来源于人类多能干细胞的再生神经细胞治疗候选药物，用于治疗癫痫。NRTX-1001包括分泌抑制性神经递质γ-氨基丁酸（GABA）的中间神经元。作为一次性给药疗法，该药物能够提供局部长期GABA信号通路抑制，以重新平衡和修复引起癫痫以及神经系统其他疾病过度兴奋的神经网络。截至目前，已有两位患者接受了治疗。在接受NRTX-1001治疗后，两名患者的癫痫发作活动在治疗后9个月和5个月时持续减少＞90%。第一例有9年癫痫发作史的患者在治疗一个月后，就再也没有发生致残性癫痫发作，该患者在治疗后记忆力也有改善。ALN-APP：公布1期临床试验的中期数据Alnylam和再生元（Regeneron）公司公布了其在研RNAi疗法ALN-APP在首个人体临床试验中获得积极中期结果。ALN-APP是一种针对淀粉样前体蛋白（APP）的RNAi疗法，用于治疗阿尔茨海默病和脑淀粉样血管病。试验结果显示，ALN-APP不但表现出良好的安全性和耐受性，而且单剂治疗快速持久地降低了脑脊液中与APP相关的生物标志物，最高剂量治疗降低幅度可高达90%。新闻稿指出，这一结果为Alnylam将RNAi递送到中枢神经系统（CNS）的C16技术平台提供了人体概念验证，有望打开RNAi疗法治疗多种神经退行性疾病的大门。BBT-207：获FDA批准开展首次人体试验Bridge Biotherapeutics公司宣布已获得FDA的批准，将开展其候选疗法BBT-207的首次人体研究。BBT-207是一种创新第四代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI），是Bridge Biotherapeutics首个自主研发的具有强活性和针对非小细胞肺癌（NSCLC）中广泛的EGFR基因突变的有效候选药物。该公司最近在2023年美国癌症研究协会（AACR）年会上披露了BBT-207的最新临床前数据。体外和体内研究结果都显示了该药物的颅内抗肿瘤活性以及疗效。总体而言，BBT-207展示出了针对NSCLC中广泛存在的EGFR突变的强大活性和疗效，包括那些在第三代EGFR-TKI治疗后出现的C797S突变。4D-150：公布1b/2a期临床试验的中期数据4D Molecular Therapeutics公司公布了其玻璃体内注射的双重基因疗法4D-150用于治疗湿性AMD的早期临床数据。湿性AMD是一种影响视网膜中央黄斑部的病症，主要由脉络膜新生血管所导致，即在黄斑部有不正常的血管增生。4D-150由表达阿柏西普和抗VEGF-C的RNAi有效载荷以及能够在玻璃体内进行递送的专有载体R100组成，能够抑制4种血管生成因子：VEGFA、B、C和PlGF。新闻稿指出，4D-150是首款旨在抑制驱动血管生成的所有四种VEGF相关分子的视网膜基因疗法。此次公布的数据显示，玻璃体内注射4D-150的耐受性良好，15名患者中有14名没有报告炎症，所有患者中均没有报告剂量限制性毒性、4D-150相关严重不良事件或低眼压。最高剂量组的效果最好，80%的患者在单次给药后的36周内不需要补充抗VEGF疗法的注射，第36周的平均视网膜中央次视野厚度（CST）改善为-92 µm，且平均最佳矫正视力（BCVA）保持稳定。ATSN-101（SAR439483）：公布1/2期临床试验的新数据Atsena Therapeutics公司公布了其用于治疗GUCY2D相关的Leber先天性黑蒙（LCA1）的在研基因疗法ATSN-101（SAR439483）的1/2期临床试验的新结果。LCA1是一种由GUCY2D基因突变引起的单基因眼病，会破坏视网膜的功能，导致早期和严重的视力障碍或失明。目前尚无批准的LCA1治疗方法。数据表明，视网膜下给药ATSN-101具有良好的耐受性，没有出现与药物相关的严重不良事件。接受最高剂量治疗的患者在治疗6个月后在视网膜敏感性、BCVA等视觉功能方面有临床意义的改善，BCVA改善大于0.3 logMAR，而未接受过治疗的眼睛的BCVA出现下降。安全性方面，没有报告与药物相关的严重不良事件，大多数治疗中出现的不良事件是轻微和短暂的。STK-002：在英国启动1/2期临床试验STK-002是Stoke Therapeutics公司开发的反义寡核苷酸疗法，用于治疗常染色体显性遗传性视神经萎缩症（ADOA）。ADOA是一种罕见的疾病，患者的双眼在十几岁时就会开始发生进行性和不可逆的视力丧失。约65%-90%的ADOA病例是由OPA1基因突变引起的，其中大部分为基因单倍剂量不足（haploinsufficiency）引起的临床表现，因为只有正常水平50%的OPA1蛋白不足以维持细胞正常的生理功能。目前，尚无获批的ADOA治疗方法。STK-002旨在通过上调OPA1基因的野生型拷贝来恢复OPA1蛋白质的表达，从而缓解甚至阻止ADOA患者的视力丧失。新闻稿指出，STK-002有望成为首个解决ADOA根本原因的疾病缓解疗法。RG6501（OpRegen）：公布1/2a期临床试验数据Lineage Cell Therapeutics公司公布了其同种异体视网膜色素上皮（RPE）细胞疗法RG6501（OpRegen）用于治疗继发于年龄相关性黄斑变性（AMD）的地理萎缩（GA）的早期临床数据。结果显示，施用OpRegen细胞后，患者眼睛的视网膜外结构和视觉功能获得了持续的改善，OpRegen细胞可以通过抵消宿主RPE细胞功能障碍和损失来为萎缩区域内剩余的视网膜细胞提供支持。此外，需要在更大规模的临床研究中进一步评估干预的最佳疾病阶段和OpRegen的目标递送位置，以确认这些初步发现。MDG1011：公布1期临床试验数据Medigene公司公布了其靶向PRAME的TCR-T细胞疗法MDG1011在高危髓系和淋巴系肿瘤中的1期临床试验数据。此次公布的结果显示，MDG1011在9名接受过大量先前治疗的患者中普遍耐受良好，未观察到神经毒性或剂量限制性毒性。9名患者中有2名在第4周时对治疗表现出了早期反应，其中1名患者在第12周时出现疾病进展。研究人员在患者接受治疗4周后在其外周血中检测到了TCR-T细胞，1名患者在第12个月时仍可检测到。ExoFlo：启动1b/2a期临床试验ExoFlo是Direct Biologics公司开发的间充质干细胞分泌的细胞外囊泡生物制品，旨在减少炎症、调节免疫系统并通过细胞再生恢复组织，用于治疗难治性肛周瘘管性克罗恩病（CD）。肛周瘘管性CD难以治愈，37%的患者患有难治性疾病，并且>90%的患者接受了多种手术干预，面临尿失禁的风险，亟待改进的疗法。Direct Biologics将启动多一项中心、单盲、随机、安慰剂对照试验以评估ExoFlo治疗难治性肛周瘘管性CD的安全性和有效性。ELU001：公布1期临床试验数据Elucida Oncology公司公布了其C’Dot偶联药物ELU001在过度表达叶酸受体α（FRα）的实体肿瘤患者中的1期临床数据。Elucida Oncology致力于利用其名为C’Dot的递送技术精准靶向和肿瘤内递送治疗药物。这一递送技术可以精准递送多种类型的治疗性药物，并且由于它的个体很小，能够在肾脏被有效清除。FRα在多种肿瘤中过度表达，包括卵巢、子宫内膜、结直肠、三阴性乳腺癌和非小细胞肺癌，但在正常组织中表达极低，使其成为靶向药物递送的有吸引力的肿瘤相关抗原。ELU001正是靶向这一靶点。此次公布的结果显示，ELU001具有差异化的安全性，避免了与靶向FRα的抗体偶联药物以及使用拓扑异构酶1有效负荷的抗体偶联药物相关的多种正常组织毒性，在试验中未观察到间质性肺病、周围神经病变、肝脏、肾脏、心脏或眼部不良事件。此外，新的临床前数据表明，ELU001还具有治疗脑转移肿瘤的潜力。AOC 1001：公布1/2期临床试验的新数据Avidity Biosciences公司公布了其用于治疗1型强直性肌营养不良（DM1）患者的在研抗体偶联寡核苷酸（Antibody Oligonucleotide Conjugates，AOCs）药物AOC 1001在1/2期临床试验中的积极结果。AOC 1001是通过Avidity的AOC平台所生产，由其专有的靶向1型转铁蛋白受体（TfR1）单克隆抗体与靶向DMPK mRNA的siRNA偶联所构成。美国FDA与欧洲药品管理局（EMA）皆授予了AOC 1001孤儿药资格，FDA还授予此疗法快速通道资格。此前公布的结果显示，该siRNA靶向疗法可有效递送至所有病患的骨骼肌，并造成平均45%致病DMPK mRNA水平下降。此次公布的新数据显示，AOC 1001在多个功能终点的评估方面获得了改善，包括肌强直（vHOT）、力量测量（上半身和下半身六个肌肉群的定量肌肉测试总分）和活动能力，并显示出良好的安全性和耐受性，大多数不良事件为轻度或中度。BI-1206：公布1/2期临床试验的新数据BioInvent公司公布了其新型FcgRIIB抗体BI-1206在非霍奇金淋巴瘤（NHL）的1/2期临床试验中的新数据。BI-1206具有独特的作用靶点，通过阻断单一抑制性抗体检查点受体FcγRIIB，从而在血液瘤和实体瘤中解锁抗癌免疫力。同时，BI-1206有望能恢复并提高利妥昔单抗或其它CD20单抗在治疗NHL疾病的活性。此次公布的结果显示，在15名可评估的患者中，7名观察到了临床缓解（完全和部分缓解），4名患者达到疾病稳定。BioInvent公司正在招募该研究的皮下给药组患者。SNS-101：IND申请获得FDA许可SNS-101是Sensei Biotherapeutics公司开发的一种条件激活的单克隆IgG1抗体，旨在低pH肿瘤微环境中选择性地阻断VISTA检查点，该检查点通过结合其受体PSGL-1来抑制T细胞。临床前研究表明，SNS-101作为单一疗法具有抑制肿瘤生长的潜力，可显著增强PD-1阻断剂的抗肿瘤作用，并降低细胞因子释放综合征的风险。Sensei公司计划评估SNS-10作为单一疗法或与再生元的PD-1抑制剂cemiplimab联合使用作为实体肿瘤患者的一种新疗法，预计在2023年年中为第一位患者给药。Naporafenib：公布1b期临床试验扩展臂的数据Erasca公司公布了其泛RAF抑制剂naporafenib联用曲美替尼治疗NRAS突变的黑色素瘤的1b期临床试验扩展臂的数据。结果显示，在经过大量前期治疗的患者中，该组合疗法展现出有希望的初步抗肿瘤活性。该组合疗法的首选剂量为200 mg naporafenib（一日两次）联用1 mg曲美替尼（一日一次），该剂量组的客观缓解率（ORR）为47%，中位反应持续时间为3.75个月，中位无进展生存期（PFS）为5.5个月。GFH009：公布1期临床试验数据SELLAS Life Sciences公司公布了其获独家授权的新一代高选择性CDK9小分子抑制剂GFH009在急性髓性白血病（AML）中的1期临床试验数据。临床前实验数据显示，GFH009对CDK9蛋白的选择性抑制率超过其它CDK亚型100倍以上。此次公布的结果显示，GFH009的药代动力学（PK）概况支持每周一次的给药；多个剂量水平下，患者骨髓中的白血病母细胞减少了50%或更多，在该研究中的最高剂量水平下，白血病母细胞减少了75%。GFH009在所有剂量水平下的安全性和耐受性良好，没有剂量限制毒性，也没有观察到明显的脱靶毒性。大家都在看药明康德为全球生物医药行业提供一体化、端到端的新药研发和生产服务，服务范围涵盖化学药研发和生产、生物学研究、临床前测试和临床试验研发、细胞及基因疗法研发、测试和生产等领域。如您有相关业务需求，欢迎点击下方图片填写具体信息。▲如您有任何业务需求，请长按扫描上方二维码，或点击文末“阅读原文/Read more”，即可访问业务对接平台，填写业务需求信息▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看）[1] Elucida Oncology Announces Positive Early Phase 1 Safety Data Along with Preclinical Data for the Treatment of Brain Metastases for ELU001, an Anti-Folate Receptor Alpha C’Dot Drug Conjugate. 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Retrieved April 25, 2023, from https://www.prnewswire.com/news-releases/bridge-biotherapeutics-receives-fda-authorization-to-proceed-with-the-first-in-human-study-of-bbt-207-a-4th-generation-egfr-tki-301804960.html[9] Atsena Therapeutics Announces Positive 6-month Data from Ongoing Phase I/II Clinical Trial of ATSN-101 in Patients with Leber Congenital Amaurosis Caused by Biallelic Mutations in GUCY2D (LCA1) . Retrieved April 25, 2023, from https://www.globenewswire.com/news-release/2023/04/25/2653762/0/en/Atsena-Therapeutics-Announces-Positive-6-month-Data-from-Ongoing-Phase-I-II-Clinical-Trial-of-ATSN-101-in-Patients-with-Leber-Congenital-Amaurosis-Caused-by-Biallelic-Mutations-in-.html[10] Stoke Therapeutics Receives Authorization to Initiate a Phase 1/2 Study of STK-002 for Autosomal Dominant Optic Atrophy (ADOA) in the United Kingdom. Retrieved April 25, 2023, from https://www.businesswire.com/news/home/20230425005243/en[11] Vaccinex Completes Enrollment in Phase 1b/2 SIGNAL-AD (Alzheimer’s Disease) Study of Pepinemab. Retrieved April 25, 2023, from https://ir.vaccinex.com/news-releases/news-release-details/vaccinex-completes-enrollment-phase-1b2-signal-ad-alzheimers[12] Erasca Announces Publication of Promising Clinical Data Supporting the Therapeutic Potential of Naporafenib in Combination with Trametinib in NRAS-Mutant Melanoma. Retrieved April 25, 2023, from https://investors.erasca.com/news-releases/news-release-details/erasca-announces-publication-promising-clinical-data-supporting[13] Parthenon Therapeutics Announces First Patient Dosed in Phase 1 Clinical Trial of PRTH-101, a Novel DDR1 Inhibitor for the Treatment of Immune-Excluded Solid Tumors. Retrieved April 25, 2023, from https://www.businesswire.com/news/home/20230425005273/en[14] Direct Biologics Receives FDA Clearance to Initiate Phase 1b/2a Clinical Trial of ExoFlo™ in Patients with Medically Refractory Perianal Fistulizing Crohn’s Disease. Retrieved April 25, 2023, from https://www.businesswire.com/news/home/20230426005284/en/[15] RG6501 (OpRegen®) Phase 1/2a Clinical Results Support the Potential for OpRegen to Slow, Stop or Reverse Disease Progression in Geographic Atrophy Secondary to Age-Related Macular Degeneration. Retrieved April 25, 2023, from https://www.businesswire.com/news/home/20230426005108/en[16] Alnylam and Regeneron Report Positive Interim Phase 1 Clinical Data on ALN-APP, an Investigational RNAi Therapeutic for Alzheimer’s Disease and Cerebral Amyloid Angiopathy. Retrieved April 26, 2023, from https://investors.alnylam.com/press-release?id=27441[17] Avenge Bio Announces Successful Completion of First Dose Level Cohort in Phase 1/2 Clinical Trial of AVB-001 for the Treatment of Ovarian Cancer. Retrieved April 25, 2023, from https://www.prnewswire.com/news-releases/avenge-bio-announces-successful-completion-of-first-dose-level-cohort-in-phase-12-clinical-trial-of-avb-001-for-the-treatment-of-ovarian-cancer-301807518.html[18] Calico Life Sciences Announces First Participant Dosed in Phase 1b Clinical Study Evaluating ABBV-CLS-7262 for the Treatment of Vanishing White Matter Disease. Retrieved April 25, 2023, from https://www.prnewswire.com/news-releases/calico-life-sciences-announces-first-participant-dosed-in-phase-1b-clinical-study-evaluating-abbv-cls-7262-for-the-treatment-of-vanishing-white-matter-disease-301807584.html[19] CONTRAFECT ANNOUNCES FIRST PATIENT DOSED IN THE PHASE 1B/2 STUDY OF EXEBACASE IN PATIENTS WITH CHRONIC PROSTHETIC JOINT INFECTIONS OF THE KNEE. Retrieved April 25, 2023, from https://ir.contrafect.com/press-releases/detail/351/contrafect-announces-first-patient-dosed-in-the-phase-1b2[20] Elicio Therapeutics Announces First Patient Dosed in Phase 1/2 Study of Lymph Node-Targeted Investigational Therapeutic Vaccine ELI-002 7P (AMPLIFY-7P) in KRAS/NRAS Mutated Solid Tumors. Retrieved April 25, 2023, from https://elicio.com/2023/04/elicio-therapeutics-announces-first-patient-dosed-in-phase-1-2-study-of-lymph-node-targeted-investigational-therapeutic-vaccine-eli-002-7p-amplify-7p-in-kras-nras-mutated-solid-tumors/[21] Avidity Biosciences Announces Positive Topline Data from AOC 1001 Phase 1/2 MARINA™ Trial Demonstrating Functional Improvement, Disease Modification and Favorable Safety and Tolerability Profile in People Living with Myotonic Dystrophy Type 1. Retrieved April 25, 2023, from https://www.prnewswire.com/news-releases/avidity-biosciences-announces-positive-topline-data-from-aoc-1001-phase-12-marina-trial-demonstrating-functional-improvement-disease-modification-and-favorable-safety-and-tolerability-profile-in-people-living-with-myotonic-dyst-301809804.html[22] 4DMT Presents Positive Interim Data from Intravitreal 4D-150 Phase 1/2 PRISM Clinical Trial in Patients with Wet AMD at ARVO 2023. Retrieved April 25, 2023, from https://www.globenewswire.com/news-release/2023/04/27/2656152/0/en/4DMT-Presents-Positive-Interim-Data-from-Intravitreal-4D-150-Phase-1-2-PRISM-Clinical-Trial-in-Patients-with-Wet-AMD-at-ARVO-2023.html免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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。版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

AACR会议临床1期临床结果临床2期

2023-04-26

·GlobeNewswire-Health Care

Medigene AG presents final Phase I data of TCR-T cell therapy MDG1011 in patients with high-risk blood cancers

MDG1011 was generally well tolerated in nine heavily pre-treated patients across three ascending dose levels No neurotoxicity or dose-limiting toxicities observed Two out of nine patients showed early response on treatment at week 4, of which one patient experienced disease progression by week 12 MDG1011 TCR-T cells detected in peripheral blood within four weeks of treatment, with detection still possible in one patient at twelve months Martinsried/Munich, April 24, 2023. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today reports final Phase I dose escalation results from first-in-human Study of HLA-A*02:01-restricted PRAME-specific T cell receptor engineered T cell (TCR-T) therapy (MDG1011) for high-risk myeloid and lymphoid neoplasms (NCT03503968). The data will be presented as an eposter (P227) at the European Society for Blood and Marrow Transplantation (EBMT) 2023 annual meeting, being held April 23-26, 2023, in Paris. Abstract title: First-in-Human Study of MDG1011, a TCR-T Cell Therapy directed against HLA-A*02:01-Restricted PRAME, for High-Risk Myeloid and Lymphoid Neoplasms (CD-TCR-001) MDG1011 is an autologous TCR-T therapy specific for a peptide fragment of PRAME (PReferentially expressed Antigen in MElanoma), a tumor antigen presented on cancer cells by human leukocyte antigen HLA-A*02:01. In the open-label, first-in-human Phase I study conducted at nine clinical centers throughout Germany, thirteen patients (ten with acute myeloid leukemia (AML), two with multiple myeloma (MM) and one with myelodysplastic syndrome and myeloproliferative neoplasm MDS/MPN)) underwent leukapheresis for TCR-T cell manufacture, with four patients succumbing to disease prior to treatment. Subsequently, nine patients with relapsed or refractory AML, MDS/MPN or MM received MDG1011 by single intravenous infusion after a lymphodepleting regimen. Patients received MDG1011 at one of three escalating dose levels (DL): 0.1 (DL1), 1.0 (DL2) or 5.0 (DL3) million TCR-transduced T cells per kg body weight. Immune monitoring of patients included quantification of PRAME levels in bone marrow (BM) and/or peripheral blood (PB) and pharmacokinetics of MDG1011 in PB. Clinical and biological data analysis Of the 124 adverse events (AEs), 54 were > Grade 3 toxicities: 31 related to lymphodepletion and 21 related to the investigational medicinal product. Severe adverse events were reported for 7 of 9 patients undergoing therapy, with two patients exhibiting cytokine release syndrome (CRS) of mild (Grade 1) to moderate (Grade 2) severity, respectively, that were manageable with concomitant IL-6 therapy. No neurotoxicity or dose-limiting toxicities were reported. Four patients died from their disease, with none considered related to MDG1011, and none at DL3 Two out of 9 patients showed early response on treatment at week 4. Of these, one AML patient treated with DL1 showed complete remission at week four, but disease progression was detected at week twelve. One patient with multilineage MDS/MPN treated with DL3 remained stable and did not show any progression to secondary AML throughout the 12-month study. MDG1011 TCR-T cells were present in PB of 6 of 8 patients within the first four weeks, with detection still possible in the MDS/MPN patient at twelve months. Four patients (3 AML, 1 MM) displayed decreased PRAME levels in BM, while one patient (MM) showed slightly elevated expression at week four. The MDS/MPN patient showed PRAME levels below baseline in PB throughout the 12-month observation period. Application of MDG1011 was generally well tolerated by heavily pre-treated patients who received up to 5 million CD8-positive PRAME-specific TCR-T cells/kg body weight. Clinical observations were corroborated by persistence of MDG1011 cells in PB and reduction of PRAME levels in PB and/or BM. Prof. Dolores Schendel, Chief Scientific Officer at Medigene: “We are pleased to report the end-of-trial results for the Phase I dose escalation study of MDG1011 which showed the potential for MDG1011 in high-risk myeloid neoplasms. We thank all the investigators and their staff who carried out this clinical trial and are indebted to the patients and their families who participated in this first-in-human study. As we have announced previously, despite these encouraging early data, in line with our strategy to focus on solid tumors, we are currently exploring the opportunity to partner MDG1011 for further clinical development.” About Medigene Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit www.medigene.com About Medigene’s End-To-End Platform Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The end-to-end platform includes multiple product enhancement technologies, (e.g. PD1-41BB Switch Receptor, Precision Pairing) and development optimization technologies (e.g. Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies. About PRAME PRAME (PReferentially expressed Antigen in MElanoma) is a tumor antigen of the cancer-testis-antigen family which is over-expressed in various solid and blood cancers. Expression in healthy tissue is limited to the testis, which itself is an immuno-privileged tissue that usually cannot be attacked by the body’s own immune cells. This renders PRAME very suitable as a target antigen for TCR-T therapies. The content above comes from the network. if any infringement, please contact us to modify.

免疫疗法临床结果细胞疗法

2023-04-24

·BioSpace

Medigene AG presents final Phase I data of TCR-T cell therapy MDG1011 in patients with high-risk blood cancers

MDG1011 was generally well tolerated in nine heavily pre-treated patients across three ascending dose levels No neurotoxicity or dose-limiting toxicities observed Two out of nine patients showed early response on treatment at week 4, of which one patient experienced disease progression by week 12 MDG1011 TCR-T cells detected in peripheral blood within four weeks of treatment, with detection still possible in one patient at twelve months Martinsried/Munich, April 24, 2023. Medigene AG (Medigene, FSE: MDG1, Prime Standard), an immuno-oncology platform company focusing on the discovery and development of T cell immunotherapies for solid tumors, today reports final Phase I dose escalation results from first-in-human Study of HLA-A*02:01-restricted PRAME-specific T cell receptor engineered T cell (TCR-T) therapy (MDG1011) for high-risk myeloid and lymphoid neoplasms (NCT03503968). The data will be presented as an eposter (P227) at the European Society for Blood and Marrow Transplantation (EBMT) 2023 annual meeting, being held April 23-26, 2023, in Paris. Abstract title: First-in-Human Study of MDG1011, a TCR-T Cell Therapy directed against HLA-A*02:01-Restricted PRAME, for High-Risk Myeloid and Lymphoid Neoplasms (CD-TCR-001) The poster will be available on Medigene's website at the start of the conference: MDG1011 is an autologous TCR-T therapy specific for a peptide fragment of PRAME (PReferentially expressed Antigen in MElanoma), a tumor antigen presented on cancer cells by human leukocyte antigen HLA-A*02:01. In the open-label, first-in-human Phase I study conducted at nine clinical centers throughout Germany, thirteen patients (ten with acute myeloid leukemia (AML), two with multiple myeloma (MM) and one with myelodysplastic syndrome and myeloproliferative neoplasm MDS/MPN)) underwent leukapheresis for TCR-T cell manufacture, with four patients succumbing to disease prior to treatment. Subsequently, nine patients with relapsed or refractory AML, MDS/MPN or MM received MDG1011 by single intravenous infusion after a lymphodepleting regimen. Patients received MDG1011 at one of three escalating dose levels (DL): 0.1 (DL1), 1.0 (DL2) or 5.0 (DL3) million TCR-transduced T cells per kg body weight. Immune monitoring of patients included quantification of PRAME levels in bone marrow (BM) and/or peripheral blood (PB) and pharmacokinetics of MDG1011 in PB. Clinical and biological data analysis Of the 124 adverse events (AEs), 54 were > Grade 3 toxicities: 31 related to lymphodepletion and 21 related to the investigational medicinal product. Severe adverse events were reported for 7 of 9 patients undergoing therapy, with two patients exhibiting cytokine release syndrome (CRS) of mild (Grade 1) to moderate (Grade 2) severity, respectively, that were manageable with concomitant IL-6 therapy. No neurotoxicity or dose-limiting toxicities were reported. Four patients died from their disease, with none considered related to MDG1011, and none at DL3 Two out of 9 patients showed early response on treatment at week 4. Of these, one AML patient treated with DL1 showed complete remission at week four, but disease progression was detected at week twelve. One patient with multilineage MDS/MPN treated with DL3 remained stable and did not show any progression to secondary AML throughout the 12-month study. MDG1011 TCR-T cells were present in PB of 6 of 8 patients within the first four weeks, with detection still possible in the MDS/MPN patient at twelve months. Four patients (3 AML, 1 MM) displayed decreased PRAME levels in BM, while one patient (MM) showed slightly elevated expression at week four. The MDS/MPN patient showed PRAME levels below baseline in PB throughout the 12-month observation period. Application of MDG1011 was generally well tolerated by heavily pre-treated patients who received up to 5 million CD8-positive PRAME-specific TCR-T cells/kg body weight. Clinical observations were corroborated by persistence of MDG1011 cells in PB and reduction of PRAME levels in PB and/or BM. Prof. Dolores Schendel, Chief Scientific Officer at Medigene: “We are pleased to report the end-of-trial results for the Phase I dose escalation study of MDG1011 which showed the potential for MDG1011 in high-risk myeloid neoplasms. We thank all the investigators and their staff who carried out this clinical trial and are indebted to the patients and their families who participated in this first-in-human study. As we have announced previously, despite these encouraging early data, in line with our strategy to focus on solid tumors, we are currently exploring the opportunity to partner MDG1011 for further clinical development.” --- end of press release --- About Medigene Medigene AG (FSE: MDG1) is an immuno-oncology platform company dedicated to developing T cell therapies to effectively eliminate cancer. Its end-to-end technology platform, built on multiple proprietary and exclusive product development and product enhancement technologies, allows Medigene to create best-in-class differentiated, T cell receptor engineered T cell (TCR-T) therapies for multiple solid tumor indications that are optimized for both safety and efficacy. This platform provides product candidates for both its in-house therapeutics pipeline and partnering. For more information, please visit About Medigene’s End-To-End Platform Medigene’s immunotherapies help activate the patient’s own defense mechanisms by harnessing T cells in the battle against cancer. Medigene’s end-to-end platform combines multiple exclusive and proprietary technologies to create best-in-class TCR-T therapies. The end-to-end platform includes multiple product enhancement technologies, (e.g. PD1-41BB Switch Receptor, Precision Pairing) and development optimization technologies (e.g. Allogeneic-HLA (Allo-HLA) TCR Priming) to aid the development of differentiated TCR-T therapies. Partnerships with multiple companies including BioNTech, 2seventy bio, and Hongsheng Sciences, continue to validate the platform’s assets & technologies. About PRAME PRAME (PReferentially expressed Antigen in MElanoma) is a tumor antigen of the cancer-testis-antigen family which is over-expressed in various solid and blood cancers. Expression in healthy tissue is limited to the testis, which itself is an immuno-privileged tissue that usually cannot be attacked by the body’s own immune cells. This renders PRAME very suitable as a target antigen for TCR-T therapies. This press release contains forward-looking statements representing the opinion of Medigene as of the date of this release. The actual results achieved by Medigene may differ significantly from the forward-looking statements made herein. Medigene is not bound to update any of these forward-looking statements. Medigene® is a registered trademark of Medigene AG. This trademark may be owned or licensed in select locations only. Medigene AG Pamela Keck Phone: +49 89 2000 3333 01 E-mail: investor@medigene.com LifeSci Advisors Sandya von der Weid Phone: +41 78 680 05 38 E-mail: svonderweid@lifesciadvisors.com Should you no longer wish to receive any information about Medigene, please inform us by e-mail (investor@medigene.com). We will then delete your address from our distribution list.

免疫疗法临床结果临床1期细胞疗法

100 项与 MDG-1011 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
骨髓增生异常综合征	临床2期	德国	MediGene AG	2019-09-16
急性髓性白血病	临床2期	德国	MediGene AG	2018-01-10
多发性骨髓瘤	临床2期	德国	MediGene AG	2017-11-30

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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


NCT03503968 (Corporate Publications) 人工标引	临床1/2期	血液肿瘤	13	MDG-1011	選積夢艱齋鑰選夢製鬱(製鬱積獵觸醖鹽衊壓構) = 獵鏇遞壓憲顧選膚鑰齋蓋膚鹹鹹夢糧遞簾繭襯 (積鹽簾獵製鏇簾觸鑰憲 ) 更多	积极	2022-02-03