A Multicenter, Open-label, Interventional Phase I Trial to Determine the Dose and Evaluate the Pharmacokinetics (PK) and Safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as Monotherapy or Following Standard of Care (SoC) for the Treatment of Somatostatin Receptor-positive Tumors in the Pediatric Population (KinLET).

The purpose of the study is to determine the appropriate pediatric dosage and evaluate the pharmacokinetics (PK) and safety of Lutetium Lu 177 Edotreotide Targeted Radiopharmaceutical Therapy (RPT) as a monotherapy or following standard of care (SoC) in participants ≥2 to <18 years of age with somatostatin receptor (SSTR)-positive tumors.

开始日期2025-01-01

申办/合作机构

ITM Solucin GmbH

NCT05918302

/ Recruiting临床3期IIT

Efficacy, Safety and Patient-reported Outcomes of Peptide Receptor Radionuclide Therapy with 177Lu-edotreotide Compared to Everolimus in Somatostatin Receptor Positive Neuroendocrine Tumors of the Lung and Thymus.

LEVEL trial aims to demonstrate the higher efficacy of 177Lu-edotreotide over everolimus in patients with well to moderately differentiated neuroendocrine tumors of the lung and thymus who require systemic therapy. It is hypothesized that 177Lu-edotreotide may significantly increase the progression-free survival (PFS) compared to everolimus in lung and thymic carcinoids.

开始日期2023-10-27

申办/合作机构

Itm Isotope Technologies Munich SE

100 项与镥[177Lu]依多曲肽相关的临床结果

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100 项与镥[177Lu]依多曲肽相关的转化医学

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100 项与镥[177Lu]依多曲肽相关的专利（医药）

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项与镥[177Lu]依多曲肽相关的文献（医药）

2024-06-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

Safety and Efficacy ofPara-Aminohippurate Coinfusion for Renal Protection During Peptide Receptor Radiotherapy in Patients with Neuroendocrine Tumors

Article

作者: Jentzen, Walter ; van Echteld, Cees J A ; Meckel, Marian ; Fendler, Wolfgang P ; Himmen, Stephan ; Coelho, Marta ; Fragoso Costa, Pedro ; Sraieb, Miriam ; Herrmann, Ken ; Moraitis, Alexandros ; Kersting, David

Para-aminohippurate, also known as p-aminohippuric acid (PAH), is used clinically to measure effective renal plasma flow. Preclinically, it was shown to reduce ¹⁷⁷Lu-DOTATOC uptake in the kidneys while improving bioavailability compared with amino acid (AA) coinfusion. We report the safety and efficacy of PAH coinfusion during peptide receptor radiotherapy in patients with neuroendocrine tumors. Methods: Twelve patients with metastatic or unresectable gastroenteropancreatic neuroendocrine tumors received ¹⁷⁷Lu-DOTATOC in 33 treatment cycles. Either 8 g of PAH or a mixture of 25 g of arginine and 25 g of lysine were coinfused. Safety was assessed by monitoring laboratory data, including hematologic and renal data, as well as electrolytes obtained before and 24 h after treatment. For radiation dosimetry, whole-body scans were performed at 1, 24, and 48 h and a SPECT/CT scan was performed at 48 h, along with blood sampling at 5 min and 0.5, 2, 4, 24, and 48 h after administration. Absorbed dose estimations for the kidneys and bone marrow were performed according to the MIRD concept. Results: In 15 treatment cycles, PAH was coinfused. No changes in mean creatinine level, glomerular filtration rate, and serum electrolytes were observed before or 24 h after treatment when using PAH protection (P ≥ 0.20), whereas serum chloride and serum phosphate increased significantly under AA (both P < 0.01). Kidney-absorbed dose coefficients were 0.60 ± 0.14 Gy/GBq with PAH and 0.53 ± 0.16 Gy/GBq with AA. Based on extrapolated cumulative kidney-absorbed doses for 4 cycles, 1 patient with PAH protection and 1 patient with AA protection in our patient group would exceed the 23-Gy conservative threshold. The bone marrow-absorbed dose coefficient was 0.012 ± 0.004 Gy/GBq with PAH and 0.012 ± 0.003 Gy/GBq with AA. Conclusion: PAH is a promising alternative to AA for renal protection during peptide receptor radiotherapy. Further research is required to systematically investigate the safety profile and radiation dosimetry at varying PAH plasma concentrations.

2024-01-01·Theranostics

Long-term Nephrotoxicity after PRRT: Myth or Reality

Article

作者: Yu, Fei ; Zhang, Jingjing ; Baum, Richard P ; Schuchardt, Christiane ; Fan, Xin ; Chen, Xiaoyuan ; Jakobsson, Vivianne

Rationale: The kidneys are commonly considered as the potential dose-limiting organ for peptide receptor radionuclide therapy (PRRT), making the risk of nephrotoxicity a primary concern. This retrospective analysis with prospective documentation and long-term follow-up aims to assess the risk of nephrotoxicity after PRRT in a large cohort of patients with neuroendocrine neoplasms (NENs) treated at our institution over the past 18 years. Methods: A total of 1361 NEN patients treated with 1-10 cycles of ¹⁷⁷Lu-DOTA-TOC/-NOC/-TATE, ⁹⁰Y-DOTA-TOC/-NOC/-TATE, DUO-PRRT (sequential administration of ⁹⁰Y- and ¹⁷⁷Lu-), or TANDEM-PRRT (combination of ⁹⁰Y- and ¹⁷⁷Lu- on the same day concomitantly) were included in this analysis. All parameters were prospectively documented in a structured database comprising over 250 items per patient and retrospectively analyzed. Kidney function, including serum creatinine, blood urea nitrogen, cGFR, and electrolytes, was evaluated before each PRRT cycle and during follow-up. Restaging was regularly performed at 6-month intervals until death. Treatment-related adverse events were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0). Results: Between 2000 and 2018, a total of 5409 cycles of PRRT were administered to 1361 NEN patients. Follow-up after complete treatment was available for 1281 patients receiving 4709 cycles of PRRT, with a median follow-up time of 69.2 months (interquartile range, 32.8-110.5 months) and a maximum follow-up time of 175 months. Baseline creatinine levels were normal in 1039/1281 (81.1%) subjects, while grade 1 (G1) renal insufficiency was present in 221/1281 (17.3%) prior to PRRT. G2 was present in 19/1281 (1.5%), and G3 in 2/1281 (0.2%). After treatment, the proportion of G3/G4 grade patients only increased from 0.2% to 0.7%. Mean creatinine levels increased from a baseline of 0.90 ± 0.30 to 1.01 ± 0.57 mg/L (80.0 ± 26.7 to 89.4 ± 50.8 μmol/L) after treatment. In our main analysis cohort of 1244 patients (4576 cycles), 200 patients experienced an increase in CTCAE creatinine grade. Age, number of treatment cycles, type of radionuclides, and length of follow-up time were the main factors affecting CTCAE creatinine grading after treatment. When comparing the subgroups treated with different radionuclides, the risk of nephrotoxicity after ⁹⁰Y treatment alone and the ⁹⁰Y/¹⁷⁷Lu combination group was higher than after ¹⁷⁷Lu treatment alone. In the ⁹⁰Y treatment subgroup, the two significant risk factors for an increased CTCAE creatinine grade were identified to be age (≥60) and a long follow-up time. Conclusions: This retrospective analysis with prospective documentation in a large cohort of 1281 NEN patients receiving 4709 cycles of PRRT co-administered with renal protection, treated through the individualized approach at a single institution over 18 years, did not reveal any evidence of long-term PRRT-related renal toxicity. The results of our study suggest that with the use of proper renal protection, nephrotoxicity due to PRRT is more likely a myth than a reality.

2023-07-01·Journal of nuclear medicine : official publication, Society of Nuclear Medicine

¹⁶¹Tb-DOTATOC Production Using a Fully Automated Disposable Cassette System: A First Step Toward the Introduction of ¹⁶¹Tb into the Clinic.

Article

作者: Landolt, Stefan ; van der Meulen, Nicholas P ; Grundler, Pascal V ; Talip, Zeynep ; Sepini, Lebogang ; Köster, Ulli ; Schibli, Roger ; Favaretto, Chiara ; Geistlich, Susanne ; Müller, Cristina

¹⁶¹Tb is an interesting radionuclide for application in the treatment of neuroendocrine neoplasms' small metastases and single cancer cells because of its conversion and Auger-electron emission. Tb has coordination chemistry similar to that of Lu; therefore, like ¹⁷⁷Lu, it can stably radiolabel DOTATOC, one of the leading peptides used for the treatment of neuroendocrine neoplasms. However, ¹⁶¹Tb is a recently developed radionuclide that has not yet been specified for clinical use. Therefore, the aim of the current work was to characterize and specify ¹⁶¹Tb and to develop a protocol for the synthesis and quality control of ¹⁶¹Tb-DOTATOC with a fully automated process conforming to good-manufacturing-practice guidelines, in view of its clinical use. Methods: ¹⁶¹Tb, produced by neutron irradiation of ¹⁶⁰Gd in high-flux reactors followed by radiochemical separation from its target material, was characterized regarding its radionuclidic purity, chemical purity, endotoxin level, and radiochemical purity (RCP) in analogy to what is described in the European Pharmacopoeia for no-carrier-added ¹⁷⁷Lu. In addition, ¹⁶¹Tb was introduced into a fully automated cassette-module synthesis to produce ¹⁶¹Tb-DOTATOC, as used for ¹⁷⁷Lu-DOTATOC. The quality and stability of the produced radiopharmaceutical in terms of identity, RCP, and ethanol and endotoxin content were assessed by means of high-performance liquid chromatography, gas chromatography, and an endotoxin test, respectively. Results: ¹⁶¹Tb produced under the described conditions showed, as the no-carrier-added ¹⁷⁷Lu, a pH of 1-2, radionuclidic purity and RCP of more than 99.9%, and an endotoxin level below the permitted range (175 IU/mL), indicating its appropriate quality for clinical use. In addition, an efficient and robust procedure for the automated production and quality control of ¹⁶¹Tb-DOTATOC with clinically applicable specifications and activity levels, that is, 1.0-7.4 GBq in 20 mL, was developed. The radiopharmaceutical's quality control was also developed using chromatographic methods, which confirmed the product's stability (RCP ≥ 95%) over 24 h. Conclusion: The current study demonstrated that ¹⁶¹Tb has appropriate features for clinical use. The developed synthesis protocol guarantees high yields and safe preparation of injectable ¹⁶¹Tb-DOTATOC. The investigated approach could be translated to other DOTA-derivatized peptides; thus, ¹⁶¹Tb could be successfully applied in clinical practice for radionuclide therapy.

项与镥[177Lu]依多曲肽相关的新闻（医药）

2025-02-22

·药智网

核药：10亿美元分子的崛起

近日，诺华公布2024年的最新业绩显示，旗下两款核药（Lutathera和Pluvicto）在过去一年共计为其贡献了21.16亿美元，且增长态势明显。其中，刚上市三年的Pluvicto 2024全年销售额达到13.92亿美元，同比增长42％，早已成为全球首个核药十亿美元分子（其前三季度累计销售额已超10亿美元）。被外界寄予厚望的Pluvicto似乎已成为核药领域的风向标，搅动了2025开年的一池春水。 1 全方位布局 RDC是一种将精准靶向分子(单抗或多肽/小分子，Ligand)和强力杀伤因子(核素，Radioisotope)用连接臂(Linker)螯合剂（Chelator）偶联在一起而设计开发的药物形态；得益于其特殊的作用机制，RDC可实现高精度诊断及在治疗疾病的过程中具有不易耐药等优点，被认为是目前核药靶向治疗领域最具潜力的发展方向之一。在全球核药市场中，诺华凭借一系列战略性收购和布局，已占据领先地位。2017年和2018年，诺华分别收购了法国公司AAA和美国公司Endocyte，从而获得了Lutathera和Pluvicto两款RDC标杆产品。这两款药物分别靶向SSTR和PSMA，用于治疗神经内分泌肿瘤和前列腺癌。根据诺华管线披露情况，目前针对Pluvicto仍有四个适应症在研，其中针对转移性激素敏感前列腺癌（mHSPC）的研究处于Ⅲ期临床阶段，预计于2025年完成并计划提交申请。结合Pluvicto当下强劲的放量势头和诺华对其在适应症扩展、准入地区扩张和商业化上的进一步布局，该药未来可期。除了已获批上市Pluvicto和Lutathera适应症扩展研究外，诺华的内部管线还包括多款创新靶点的Lu-177（如靶向FAP的AAA614和靶向GRPR的AAA603）。研究显示，FAP在肺癌、胰腺癌等多种实体瘤中高表达，而GRPR在乳腺癌、前列腺癌、胶质瘤等患者的肿瘤中呈过表达，这些特点可以为放射性配体开辟更广阔的临床应用空间。目前，这两款药物正在针对多种实体瘤开展I/Ⅱ期临床试验。除了靶点创新外，诺华还将目光锁定在当前炙手可热的α核素-Ac-225身上。α核素与β核素相比，α核素放射性药物用于肿瘤治疗具有独特的优势，包括肿瘤杀灭效果好且不易复发；α核素射程短，对正常组织损伤极小且几乎无副作用，安全性更高。另外α核素杀伤癌细胞的同时可以引发肿瘤免疫反应，与免疫疗法有相互促进的作用，使肿瘤治疗达到“一加一大于二”的效果。作为α核素的Ac-225的半衰期为9.9天，长于Lu-177的6.647天，生产、治疗时间更为充足，并且基于其释放的α粒子的特性，结合Ac-225开发的药物，有效性和安全性方面在理论上会比Lu-177更有优势。 AAA817是一款Ac-225标记的靶向PSMA的RDC，即将进入临床Ⅱ/Ⅲ期，也是诺华在研核药中进展最快的资产，有望接力Lutathera、Pluvicto这两款诺华的RDC明星核药，成为下一款RDC“重磅炸弹”。除了AAA817外，诺华还布局了下一代Ac-225核药Ac-PSMA-R2，在2023年末启动了无论是否接受过177Lu-PSMA靶向治疗的转移性激素敏感性前列腺癌（mHSPC）和转移性去势抵抗性前列腺癌（mCRPC）患者的临床I/Ⅱ期试验，预计2027年完成此项临床研究。此外，尝到“甜头”后诺华还在持续加大投资与合作力度，2024年4月和5月先后达成两项总计46.5亿美元的合作，包括与PeptiDream共同开发多款大环肽靶向偶联核药，以及收购Mariana Oncology加码放射性配体疗法。 2 MNC纷纷加码从全球市场来看，RDC凭借其作为唯一实现诊疗一体化的核药类型的优势，已成为市场增长的核心引擎。根据BBC Research的数据显示，RDC的全球市场规模预计将在2026年达到175亿美元。面对日益增长的全球核药市场这块“肥肉”，恐怕没有哪家MNC想错过。拜耳作为较早布局核药赛道的MNC，早在2009年就与Algeta联合开发Xofigo（氯化镭223），并于2013年获批上市，用于治疗晚期骨转移型去势抵抗性前列腺癌。Xofigo虽然也是核药但与诺华的镥-177并不完全相同，Xofigo是全球首个α粒子辐射放射性治疗药物。除此之外，拜耳仍在专注于开发靶向α粒子的疗法。目前拜耳共有2个处于早期临床阶段RDC在研，且都靶向α核素225Ac，启动针对mCRPC的临床I期试验，设置了多个队列，其中包括177Lu-PSMA耐药的患者。礼来早在2006年便开始关注核药，并成为近两年来核药领域最活跃的金主之一。就在2023年9月，礼来以1.75亿美元投资核药研发公司Mariana Oncology，而就在一个月后，以14亿美元收购核药生物技术公司Point Biopharma。进入2024年，礼来先在5月宣布与Aktis Oncology达成多靶点发现合作协议，使用Aktis的新型微蛋白技术平台生产抗肿瘤放射性药物。随后又宣布与Radionetics Oncology达成战略合作，推进Radionetics的专有GPCR靶向小分子放射性药物研发进展。而根据协议条款，Radionetics收到了1.4亿美元预付款，而作为战略合作的一部分，礼来还拥有未来以10亿美元收购Radionetics的独家选择权。2025开年之际，礼来又与AdvanCell达成的协议，双方将整合AdvanCell专有的Pb212（铅-212）生产技术与核素开发基础设施，以及礼来的药物候选项目和丰富的药物开发经验，共同推动更多靶向α放射性核素疗法的开发，并加速其临床进展。除了诺华、拜耳和礼来，其他跨国药企如阿斯利康、默沙东、强生、罗氏和赛诺菲等也通过股权投资、技术引进等方式积极进入核药领域，近年来百亿美元的核药赛道持续升温，已经成为全球制药巨头们的必争之地。 3 国内企业加快布局在过去相当长的一段时间里，中国核药市场呈现出双雄争霸的竞争格局，中国同辐和东诚药业作为行业巨头，长期占据主导地位。然而，近年来，这一格局正在悄然发生变化。随着核药市场的潜力逐渐被挖掘，越来越多的新鲜血液涌入这一领域。如今，包括恒瑞医药、远大医药、先通医药、瑞迪奥、辐联医药、核欣医药等在内的近20家药企纷纷加速布局核药赛道。这些新兴力量凭借敏锐的市场洞察力和强大的研发能力，迅速崭露头角，成为推动中国核药市场发展的新生力量。与此同时，它们也凭借自身的优势和潜力，赢得了资本市场的高度关注与青睐。东诚药业是国内核药全产业链布局的标杆企业，拥有核素供应、药物孵化、生产配送等五大平台，覆盖国内93.5%人口的核医学需求。核药方面，核素药物产品丰富，主要产品云克注射液（锝[99Tc]亚甲基二膦酸盐注射液）是中国自主研发的用于类风湿性关节炎（RA）临床治疗的核素药物，而碘[131I]化钠口服溶液和碳[14C]尿素胶囊是临床上最常用的核药品种之一。此外，东诚药业近年来着力打造1.1类放射性诊疗一体化药物创新平台—烟台蓝纳成，其具有放射性诊疗一体化药物创新研发和全球领先的纳米递送技术的特点，适应症涵盖前列腺癌、胃癌、结直肠癌、鼻咽癌等多种癌症的诊断与治疗产品，其中部分产品进行中美双报，靶向PSMA诊断药物氟[18F]思睿肽注射液正在进行Ⅲ期临床试验，靶向FAP的诊断用药物氟[18F]纤抑素注射液已完成I期临床试验，靶向FAP的177Lu-LNC1004注射液已经在2023年分别取得了美国、新加坡和中国的临床批件，并在去年11月获得了FDA授予的快速通道资格，用于治疗接受过一种及以上酪氨酸激酶抑制剂的转移性碘-131难治性分化型甲状腺癌患者。远大医药作为国内RDC领域的领头企业，通过全球化并购与合作（如收购Sirtex、参股Telix、合作德国ITM），构建了覆盖肿瘤诊疗一体化的核药平台。其管线包括10款全球创新产品，涵盖68Ga、177Lu、131I等多种核素，适应症覆盖肝癌、前列腺癌等8大癌种。目前已有三款RDC药物进入Ⅲ期临床，包括诊断前列腺癌的产品TLX591-CDx、诊断透明细胞肾细胞癌产品TLX250-CDx，以及治疗GEP-NETs的产品ITM-11。截至目前，远大医药是进入中国Ⅲ期临床研究中诊断和治疗类RDC创新药储备最多的企业。 “医药一哥”恒瑞医药也算是比较早布局核药赛道的玩家，恒瑞医药在2020年成立了天津恒瑞，后者已布局5款核药管线，包括三款治疗用核药HRS-4357、镥[177Lu]氧奥曲肽注射液和HRS-6768，以及两款诊断用核药HRS-9815、镓[68Ga]伊索曲肽注射液。其中，HRS-9815用于前列腺癌诊断、HRS-4357用于转移性去势抵抗性前列腺，均靶向PSMA。而近期获批临床的HRS-6768则是一款靶向成纤维细胞激活蛋白α（FAP-α）的RDC。去年5月，中药龙头云南白药子公司云核医药的1类新药INR101注射液获得NMPA临床试验默示许可，正式宣告杀入核药赛道。INR101注射液是云核医药研发的化学1类放射性诊断类创新药，适用于前列腺癌患者PSMA阳性病灶的PET成像。与此同时，国内核药新兴力量也正走入舞台中间。智核生物、辐联医药、核欣医药、晶核生物、禾泰健宇、诺宇医药、新旭医药等也各具特色，有望成为核药赛道的重要玩家。参考来源： [1]Next generation radiotheranostics promoting precision medicine. [2]Radiotheranostics in oncology:current challenges and emerging opportunities. [3]Radiopharmaceutical therapy in cancer:clinical advances and challenges.- [4]《诺华管线梳理》Pharma知产视界 [5]《巨头重注核药赛道》医曜声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。责任编辑 | 史蒂文合作、投稿、转载开白 | 马老师 18323856316（同微信）阅读原文，是受欢迎的文章哦

免疫疗法临床3期并购临床2期

2025-01-29

·药明康德

多肽偶联药物达到3期临床主要终点，计划递交新药申请

▎药明康德内容团队编辑 ITM Isotope Technologies公司日前宣布，其专有的靶向放射性疗法ITM-11，在治疗无法手术切除的进展性1级或2级胃肠胰神经内分泌肿瘤（GEP-NETs）患者的3期临床试验COMPETE中获得积极的顶线结果。数据显示，ITM-11与标准治疗靶向药物相比，达到了延长患者无进展生存期（PFS）这一主要终点。ITM-11耐受性良好，安全性结果令人满意。 COMPETE是一项前瞻性、随机、含活性对照、开放标签的3期临床试验，旨在评估ITM-11与依维莫司（everolimus）这一标准治疗方案相比的疗效和安全性。ITM-11由镥177（一种发射β射线的放射性同位素）和edotreotide组成。Edotreotide是一种生长抑素受体（SSTR）激动剂。 COMPETE试验的次要终点包括客观缓解率、总生存期和生活质量评估，以及对ITM-11在肿瘤与健康组织中吸收剂量的评估。ITM公司计划将这些结果提交至未来的医学会议进行展示，并预计在2025年与FDA讨论潜在新药申请（NDA）的提交。神经内分泌肿瘤是一种罕见的癌症，GEP-NETs起源于神经内分泌系统，由神经细胞和激素分泌细胞组成。GEP-NETs可发生在胃肠道和胰腺的任何部位，包括胃、小肠、结肠、直肠和阑尾。由于许多患者无症状并在晚期出现转移性疾病时才被确诊，治疗选择仍存在巨大未满足的医疗需求。 ITM-11是一种放射性同位素标记的肽偶联药物，能够将β射线靶向递送至SSTR阳性肿瘤细胞中，同时避免对健康器官和组织的损伤。ITM-11通过静脉注射给药，由177镥和edotreotide组成。基于一项回顾性2期研究的积极结果，ITM-11已获得欧盟和美国的孤儿药资格，并在美国获得GEP-NETs适应症的快速通道资格。 ▲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： [1] ITM Announces Positive Topline Results of Phase 3 COMPETE Trial with ITM-11, a Targeted Radiopharmaceutical Therapy, in Patients with Grade 1 or Grade 2 Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs). Retrieved January 28, 2025, from https://www.globenewswire.com/news-release/2025/01/28/3016150/0/en/ITM-Announces-Positive-Topline-Results-of-Phase-3-COMPETE-Trial-with-ITM-11-a-Targeted-Radiopharmaceutical-Therapy-in-Patients-with-Grade-1-or-Grade-2-Gastroenteropancreatic-Neuroe.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

放射疗法临床3期临床结果孤儿药临床2期

2025-01-28

·PipelineReview

ITM Announces Positive Topline Results of Phase 3 COMPETE Trial with ITM-11, a Targeted Radiopharmaceutical Therapy, in Patients with Grade 1 or Grade 2 Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs)

GARCHING / MUNICH, Germany I January 28, 2025 I ITM Isotope Technologies Munich SE (ITM), a leading radiopharmaceutical biotech company, today announced positive topline results from its Phase 3 COMPETE trial in patients with inoperable, progressive Grade 1 or Grade 2 gastroenteropancreatic neuroendocrine tumors (GEP-NETs). The data showed that ITM-11 (n.c.a. 177 Lu-edotreotide), a proprietary, synthetic, targeted radiotherapeutic agent, met the primary endpoint of prolonging progression-free survival (PFS) when compared to everolimus, a targeted molecular therapy. ITM-11 was well-tolerated with favorable safety results observed. COMPETE is a prospective, randomized, controlled, open-label Phase 3 trial evaluating the efficacy and safety of ITM-11 compared to everolimus, a standard of care treatment. ITM-11 is comprised of non-carrier-added (n.c.a.) lutetium-177, a therapeutic β-emitting radioisotope, and edotreotide, a somatostatin receptor (SSTR) agonist. The trial enrolled 309 patients with Grade 1 or Grade 2 inoperable, progressive, somatostatin receptor-positive neuroendocrine tumors of gastroenteric or pancreatic origin (Ki-67 ≤20%). Patients were randomized 2:1 to receive 7.5 GBq of ITM-11 with a nephroprotective amino acid solution every three months for a maximum of four cycles, or everolimus 10 mg daily for up to 30 months, or until disease progression. The COMPETE trial was conducted at multiple sites throughout the world. “With COMPETE, this marks the first time that a targeted radiopharmaceutical therapy has demonstrated improved progression-free survival compared to a targeted molecular therapy, everolimus, in patients with Grade 1 and Grade 2 gastroenteropancreatic neuroendocrine tumors in a Phase 3 clinical trial. The patients included represent a real-life scenario, and the COMPETE study evaluates the important question of which therapy might be used first to provide greater benefit to patients,” said Jaume Capdevila, MD, PhD, study investigator and senior medical oncologist at Vall d’Hebron University Hospital, Barcelona . “As a clinician, I am highly encouraged by these data and look forward to seeing further results.” “We want to thank the patients, families and caregivers, and investigators for their commitment to and trust in this trial. People with GEP-NETs, whose journey from diagnosis to proper treatment can take years, remain in significant need of more robust, data-driven treatment options to maximize outcomes. The successful COMPETE data support ITM-11’s potential and we believe mark an important milestone for patients and for ITM,” said Dr. Andrew Cavey, CEO of ITM . “Our organization now has demonstrated both early and late-stage clinical development capabilities that complement our leadership in global isotope manufacturing.” Secondary endpoints in the COMPETE trial include objective response rate, overall survival, and quality of life assessments. Additionally, dosimetry was used to assess the absorbed ITM-11 dose in tumors compared to that in healthy tissue to enhance monitoring of the patient’s safety and efficacy. These dosimetry data and secondary endpoints, along with subgroup analyses, are currently being evaluated. The company plans to submit the results for presentation at a future medical meeting and anticipates discussing a potential New Drug Application (NDA) submission with the FDA in 2025. In addition to the COMPETE trial, ITM-11 is being evaluated in a Phase 3 trial (COMPOSE) in patients with well-differentiated, aggressive Grade 2 or Grade 3, SSTR-positive GEP-NET tumors. The COMPOSE trial is a prospective randomized, controlled, open-label trial evaluating the efficacy, safety and patient-reported outcomes of ITM-11 as first or second line treatment compared to physician’s choice standard of care chemotherapy. Additional clinical programs with ITM-11 include a Phase 1 pediatric trial in SSTR-positive tumors (KinLET) and a Phase 3 investigator-sponsored trial in lung and thymus neuroendocrine tumors (LEVEL). About GEP-NETS Neuroendocrine tumors (NETs) are a rare form of cancer, with an estimated 8 new cases per 100,000 individuals diagnosed each year in the U.S. and 9 cases per 100,000 in Europe. The incidence of NETs has steadily increased over recent decades, resulting, in part, from improved diagnosis. Gastroenteropancreatic neuroendocrine tumors (GEP-NETS) originate in the neuroendocrine system, and are made up of nerve cells and hormone-producing cells. They can occur anywhere in the GI tract and pancreas, including the stomach, small intestine, colon, rectum, and appendix. There is still a high unmet medical need for treatment options, as many patients are asymptomatic and diagnosed at a late stage with metastatic disease. About ITM-11 (n.c.a. 177 Lu-edotreotide) ITM-11 is a radiolabeled peptide conjugate that delivers beta radiation specifically to SSTR-positive tumor cells, sparing healthy organs and tissue. ITM-11, delivered intravenously, is comprised of non-carrier-added lutetium-177, a therapeutic β-emitting radioisotope, and edotreotide, a synthetic SSTR agonist. ITM-11 was granted orphan drug designation in the EU and the US, and fast track designation in the US for the treatment of GEP-NETs, based on positive results from a retrospective Phase 2 study 1 with 177 Lu-edotreotide. About ITM Isotope Technologies Munich SE ITM, a leading radiopharmaceutical biotech company, is dedicated to providing a new generation of radiopharmaceutical therapeutics and diagnostics for hard-to-treat tumors. We aim to meet the needs of cancer patients, clinicians and our partners through excellence in development, production and global supply. With improved patient benefit as the driving principle for all we do, ITM advances a broad precision oncology pipeline, including multiple Phase 3 studies, combining the company’s high-quality radioisotopes with a range of targeting molecules. By leveraging our two decades of pioneering radiopharma expertise, central industry position and established global network, ITM strives to provide patients with more effective targeted treatment to improve clinical outcome and quality of life. www.itm-radiopharma.com References: SOURCE: ITM

临床结果临床3期快速通道孤儿药临床2期

100 项与镥[177Lu]依多曲肽相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
SSTR阳性胃肠胰神经内分泌肿瘤	临床3期	中国	ITM Solucin GmbH	2025-02-11
SSTR阳性胃肠胰神经内分泌肿瘤	临床3期	中国	远大医药（中国）有限公司	2025-02-11
肺神经内分泌肿瘤	临床3期	法国	Itm Isotope Technologies Munich SE	2023-10-27
肺神经内分泌肿瘤	临床3期	意大利	Itm Isotope Technologies Munich SE	2023-10-27
肺神经内分泌肿瘤	临床3期	西班牙	Itm Isotope Technologies Munich SE	2023-10-27
生长抑素受体阳性神经内分泌肿瘤	临床3期	法国	Itm Isotope Technologies Munich SE	2023-10-27
生长抑素受体阳性神经内分泌肿瘤	临床3期	意大利	Itm Isotope Technologies Munich SE	2023-10-27
生长抑素受体阳性神经内分泌肿瘤	临床3期	西班牙	Itm Isotope Technologies Munich SE	2023-10-27
胸腺肿瘤	临床3期	法国	Itm Isotope Technologies Munich SE	2023-10-27
胸腺肿瘤	临床3期	意大利	Itm Isotope Technologies Munich SE	2023-10-27

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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


NCT03049189 (COMPETE, Company_Website) 人工标引	临床3期	胃肠胰神经内分泌肿瘤	309	ITM-11	鹹齋鹹襯淵觸製鬱簾製(鬱鹽艱壓餘餘觸願鏇艱) = ITM-11 demonstrating clinically relevant and statistically significant benefit in PFS compared to everolimus 鏇蓋鏇膚簾構範鹹鹽願 (網壓壓窪構選構簾壓築 ) 达到	积极	2025-01-28
				Everolimus
NCT04194125 (ESMO 12023 \| ESMO 22023) 人工标引	临床2期	神经内分泌肿瘤	21	177Lu DOTATOC+ CAPTEM	選簾淵積夢廠醖願窪鹹(窪醖積廠鹽積選簾製齋) = 繭艱醖齋膚網選構範襯齋廠觸選夢鹽夢廠築醖 (鑰觸獵糧淵糧醖餘鹹構, 16.0 ~ NR) 更多	积极	2023-10-22
				177Lu DOTATOC+ CAPTEM (panNET)	選簾淵積夢廠醖願窪鹹(窪醖積廠鹽積選簾製齋) = 構糧艱築淵齋醖鹹襯襯齋廠觸選夢鹽夢廠築醖 (鑰觸獵糧淵糧醖餘鹹構, 14.0 ~ NR)
SNMMI2023	N/A	胃肠胰神经内分泌肿瘤	-	4 cycles of PRRT	鹹鬱鹹壓獵顧鑰醖願觸(醖艱觸壓觸製範窪顧鏇) = 27 of these 36 patients (75%; 14 SI-NET; 4 CUP-NET; 9 P-NET) experienced PD in iStaging 餘淵鏇蓋壓廠齋夢鹹衊 (鹹網廠鑰繭蓋鏇顧鬱簾 ) 更多	-	2023-08-28
SNMMI2022	N/A	胃肠胰神经内分泌肿瘤	-	[177Lu]DOTATOC (GEP-NET patients)	鑰鑰糧繭網廠憲鏇餘簾(構獵鹽繭餘構廠衊積選) = 顧廠積選蓋築夢顧鑰遞淵齋鏇築鹹糧憲蓋積鑰 (觸醖鏇顧繭鹽艱製窪網 ) 更多	-	2022-08-08
SNMMI2019	N/A	-	-	Lu-177 DOTA-LM3	蓋夢願鹽鹹範鑰糧憲獵(網製襯網壓窪鑰獵製蓋) = 構憲餘製網繭鹹糧築鏇簾齋膚積齋觸鏇顧簾遞 (選鹽餘鹹夢觸觸顧鏇淵 ) 更多	-	2019-05-21
				Lu-177 DOTATOC	蓋夢願鹽鹹範鑰糧憲獵(網製襯網壓窪鑰獵製蓋) = 淵築簾襯醖齋繭簾醖壓簾齋膚積齋觸鏇顧簾遞 (選鹽餘鹹夢觸觸顧鏇淵 ) 更多
NCT03049189 (COMPETE, ESMO2018)	临床3期	胃肠胰神经内分泌肿瘤	300	Everolimus	鏇選淵襯壓艱餘膚齋網(觸構壓積憲遞選鑰齋願) = 蓋窪獵艱艱廠顧齋廠夢鹹壓鬱淵夢餘選衊衊觸 (餘繭鬱膚鏇觸鹹廠齋衊 )	-	2018-10-21