A Phase 2 Open Label Study to Evaluate the Safety and Effectiveness of 212Pb-DOTAMTATE in Subjects With Somatostatin Receptor Expressing Neuroendocrine Tumors

Multicenter Phase 2 study of 212Pb-DOTAMTATE enrolling adult subjects with positive somatostatin positive neuroendocrine tumors with either no prior history of peptide receptor radionuclide therapy (PRRT naive) or prior history of peptide receptor radionuclide therapy (Previous PRRT)

开始日期2021-12-21

申办/合作机构

Orano Med LLC

[+1]

NCT03466216

/ Terminated临床1期

A Phase 1, Non-Randomized, Open-Label, Dose Escalation, Single-Center Study to Determine the Safety, Bio-distribution, and Preliminary Effectiveness of AlphaMedix™ in Adult Subjects With SSRT(+) NETs.

AlphaMedix™ (²¹²Pb-DOTAMTATE) is a radiotherapeutic drug indicated in subjects with unresectable, metastatic somatostatin receptor (SSTR) positive neuroendocrine tumors (NETs). Because 212Pb is an in vivo generator of alpha particles, it is particularly suitable for SSTR therapy applications.
This drug addresses an unmet need in the field of peptide receptor radionuclide therapy (PRRT) for NETs. Substitution of an alpha emitter (²¹²Pb) for the beta emitters currently being used (i.e., 177Lu or 90Y) will provide significantly higher Linear Energy Transfer (LET) and a shorter path length. Higher LET particles should cause more tumor cell death. Shorter path length should result in less collateral damage of the normal tissue and therefore less side effects for subjects receiving the drug.

开始日期2018-02-05

申办/合作机构

Orano Med LLC

100 项与 212Pb-AR-RMX 相关的临床结果

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100 项与 212Pb-AR-RMX 相关的转化医学

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100 项与 212Pb-AR-RMX 相关的专利（医药）

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项与 212Pb-AR-RMX 相关的文献（医药）

2025-12-01·APPLIED RADIATION AND ISOTOPES

Activity standardization and determination of nuclear decay data of 212Pb at LNE-LNHB and first measurements in the SIR at BIPM

Article

作者: Michotte, C ; Coulon, R ; Chambon, L ; Loidl, M ; Amiot, M-N ; Bobin, C ; Carceller, C ; Sabot, B ; Thiam, C ; Pierre, S ; Boyer, B ; Morelli, S ; Courte, S ; Lourenço, V ; Dulieu, C

Lead-212/Bismuth-212 is a promising radiopharmaceutical with high therapeutic potential for Targeted Alpha Therapy. In this paper, the activity standardization of ²¹²Pb in equilibrium with its progeny was addressed by means of several measurement techniques at LNE-LNHB using a radioactive solution of ²¹²Pb-DOTAMTATE supplied by Orano Med (France). The primary standard was established by liquid scintillation counting using the Triple-to-Double Coincidence Ratio (TDCR) method and transferred to the Vinten 671 ionization chamber. The experimental calibration coefficients were compared to Monte Carlo simulations using the Penelope and Geant4 codes. An ampoule filled with a standardized solution of ²¹²Pb was sent to the BIPM for a submission to the International Reference System (SIR). The resulting equivalent activity was compared to the value calculated from the SIRIC software. A new measurement of the half-life of ²¹²Pb using a Centronic IG11 IC is presented. New γ-photon intensities based on γ-spectrometry were also measured. The present study on the metrological traceability of the radiopharmaceutical ²¹²Pb is an important outcome in the framework of the European project EPM AlphaMet (Metrology for Emerging Targeted Alpha Therapies).

2022-09-01·JOURNAL OF NUCLEAR MEDICINE1区 · 医学

Targeted α-Emitter Therapy with ²¹²Pb-DOTAMTATE for the Treatment of Metastatic SSTR-Expressing Neuroendocrine Tumors: First-in-Humans Dose-Escalation Clinical Trial

1区 · 医学

Article

作者: Tworowska, Izabela ; Torgue, Julien ; Delpassand, Ebrahim S ; Núñez, Rodolfo ; Hurt, Jason ; Shafie, Afshin ; Esfandiari, Rouzbeh

Peptide receptor radiotherapy with somatostatin analogs has been successfully used for years as a treatment for somatostatin-overexpressing tumors. Treatment of neuroendocrine tumors (NETs) with the β-particle emitter ¹⁷⁷Lu-DOTATATE is currently considered the standard of care for subjects with gastroenteropancreatic NETs. Despite the success of ¹⁷⁷Lu-DOTATATE, there remains significant room for improvement in terms of both safety and efficacy. Targeted α-emitter therapy with isotopes such as ²¹²Pb has the potential to improve both. Here, we present the preliminary results of the phase 1 first-in-humans dose-escalation trial evaluating ²¹²Pb-DOTAMTATE (a bifunctional metal chelator [DOTAM] and the SSTR-targeting peptide [TATE]) in patients with somatostatin receptor-positive NETs. Methods: Twenty subjects with histologically confirmed NETs, prior positive somatostatin analog scans, and no prior history of ¹⁷⁷Lu/⁹⁰Y/¹¹¹In peptide receptor radiotherapy, with different primary sites of the disease, were enrolled. Treatment began with single ascending doses of ²¹²Pb-DOTAMTATE, with subsequent cohorts receiving an incremental 30% dose increase, which was continued until a tumor response or a dose-limiting toxicity was observed. This was followed by a multiple ascending dose regimen. The recommended phase 2 dose regimen consisted of 4 cycles of 2.50 MBq/kg (67.6 μCi/kg) of ²¹²Pb-DOTAMTATE administered at 8-wk intervals, intravenously. Results: Ten subjects received the highest dose, 2.50 MBq/kg/cycle (67.6 μCi/kg/cycle). Treatment was well tolerated, with the most common treatment-emergent adverse events being nausea, fatigue, and alopecia. No serious treatment-emergent adverse events were related to the study drug, and no subjects required treatment delay or a dose reduction. An objective radiologic response of 80% was observed for the first 10 subjects treated at the recommended phase 2 dose. Conclusion: Targeted α-therapy with ²¹²Pb-DOTAMTATE has been shown to be well tolerated. Preliminary efficacy results are highly promising. If these results are confirmed in a larger, multicenter clinical trial, ²¹²Pb-DOTAMTATE would provide a substantial benefit over currently Food and Drug Administration-approved therapies for patients with metastatic or inoperable SSTR-expressing NETs regardless of the grade and location of the primary tumor.

2019-05-01·MOLECULAR CANCER THERAPEUTICS

Preclinical Investigation of 212Pb-DOTAMTATE for Peptide Receptor Radionuclide Therapy in a Neuroendocrine Tumor Model

Article

作者: Tworowska, Izabela ; Torgue, Julien J. ; Stallons, Tania A. Rozgaja ; Saidi, Amal ; Delpassand, Ebrahim S.

Abstract:

Somatostatin analogues have been examined as a treatment for somatostatin receptor overexpressing tumors for years; specifically, octreotate (TATE) and octreotide (TOC). Several versions of these analogues coupled to beta or gamma nuclides are currently used as imaging agents, as treatments with peptide receptor radionuclide therapy (PRRT) for patients with neuroendocrine tumors or are being explored in preclinical and clinical settings. Our study describes the use of 212Pb-DOTAMTATE, the octreotate analogue, in combination with 212Pb, the parent of an alpha emitter. Preclinical studies demonstrated tumor targeting of 212Pb-DOTAMTATE of >20% ID/g up to 24 hours post drug injection. The addition of kidney protection agents, including l-lysine and l-arginine decreases drug accumulation in the kidneys and the addition of ascorbic acid to the chelation mixture reduces oxidation of the drug product. 212Pb-DOTAMTATE displays a favorable toxicity profile with single-dose injections of 20 μCi showing 100% survival and with nontoxic cumulative doses up to 45 μCi, when fractionated into three smaller doses of 15 μCi. In an initial efficacy study, a single 10 μCi injection of 212Pb-DOTAMTATE extended the mean survival 2.4-fold. Efficacy was enhanced by giving three treatment cycles of 212Pb-DOTAMTATE and reducing the time between injections to two weeks. Efficacy was optimized further by the addition of a chemo-sensitizing agent, 5-fluorouracil, given in combination with three cycles of 10 μCi 212Pb-DOTAMTATE. These conditions led to 79% of the animals being tumor free at the end of the 31-week study suggesting that 212Pb-DOTAMTATE alone or in combination with a chemotherapeutic may have positive clinical implications.

项与 212Pb-AR-RMX 相关的新闻（医药）

2025-10-30

·研发客

中国RDC商业化爆发前夕：本土产品有望率先上市

// • 诺华的Pluvicto拟推进至更早期前列腺癌的治疗； • 赛诺菲AlphaMedix治疗GEP-NETs的研究凸显搭载α射线核素RDC的优势； • 礼来、BMS和阿斯利康近两年达成的数十亿美元RDC相关交易都是涉及α射线核素的疗法； • 诊疗一体化方案是RDC领域玩家们的布局重点； • 先通医药的XTR008的III期试验贴近本土GEP-NETs疾病特征与治疗需求，有望明年在国内上市。 2025ESMO其他文章后PD-(L)1时代，免疫联合如何持续发力？放射性药物偶联物（RDC）正从靶向治疗的技术深水区加速突围，开始进入临床突破与商业化加速并行的新阶段。在今年的ESMO（欧洲肿瘤内科学会）大会上，RDC继续发力，特别是在前列腺癌和神经内分泌肿瘤（NETs）这两大RDC主战场，诺华、赛诺菲、ITM等主要玩家发布的突破性临床数据再次印证了其精准治疗价值。中国公司开始与MNC同台争辉。先通医药凭借自研创新RDC候选产品XTR008的III期研究成果入选今年ESMO“突破性摘要”。作为首个国产原研治疗用RDC，有望明年在国内上市。以更贴近中国人群的试验设计，填补国内NETs治疗型RDC的空白。拓展阅读蓄谋已久的核药全球抢核素透过近两年MNC的RDC交易倾向和ESMO上公布的新数据，可以看出，在当前多数治疗型RDC都是搭载β射线核素的背景下，疗效和安全性相对更好的搭载α射线核素的RDC产品开始走向C位。 2025年研发客临床年会将于11月启幕，精彩论坛话题提前揭晓（左右滑动查看） Pluvicto继续扩大患者覆盖范围据诺华官网的数据，包括美国、中国和日本在内的8个国家，每年约超17万名男性确诊为转移性激素敏感性前列腺癌（mHSPC）。多数患者20个月内进展为转移性去势抵抗性前列腺癌（mCRPC），且进展后患者负担加重、生活质量下降、预期寿命不足两年。其中，超80%患者高度表达前列腺特异性膜抗原（PSMA）。诺华在ESMO上公布的Ⅲ期PSMAddition研究结果显示，在PSMA阳性的mHSPC患者中，与单用标准治疗（SoC）相比，联合Pluvicto可延缓疾病进展——初步分析显示，影像学进展或死亡风险降低28%，放射学无进展生存期（rPFS）获益在所有预设亚组中均保持一致。联合方案在总生存期（OS）方面呈现早期积极获益趋势（HR 0.84; 95% CI: 0.63, 1.13），随访将持续至数据成熟。这是继PSMAfore和VISION研究之后，Pluvicto第三次取得阳性Ⅲ期研究结果，安全性和耐受性与其在前2项研究已报告的特征一致。Pluvicto联合SoC组≥3级不良事件 (AE) 的比例为50.7%，而单独使用SoC组为43%。不过，据医学杂志AJMC报道，有行业专家质疑交叉试验设计能否得出明确的总生存期结论，以及显示生活质量“未受负面影响”的数据是否真正代表积极结果。该行业专家还指出，使用Pluvicto 8个月后存在影响其他器官的风险，从而可能损害患者生活质量。 PSMAddition研究的PI之一、威尔康奈尔医学院Scott Tagawa教授回应称，随着更多长期数据的积累，这一问题将得到解决。他表示，期待后续分析能深入剖析患者报告结局的各个组成部分，同时评估计划中的次要和探索性终点指标，包括影像学检查以及肿瘤和血液生物标志物的检测结果。 Pluvicto作为唯一获批用于治疗PSMA阳性mCRPC的RDC疗法，2024年销售额超13.92亿美元，同比增长42%。据诺华最新发布的财报，Pluvicto今年前三季度的销售额为13.89亿美元，已近似达到2024年全年的水平。今年3月，Pluvicto凭借在PSMAfore研究中的显著获益，获FDA批准用于化疗前的mCRPC治疗，而PSMAddition研究结果进一步显示其在疾病早期阶段的mHSPC中的应用潜力。诺华计划于年底前将这些数据递交给监管机构。同时，诺华还在开展Pluvicto用于治疗前列腺癌寡转移的研究，未来有望进一步扩大患者覆盖范围。在国内，Pluvicto尚未获批上市，诺华已于今年4月向CDE递交二线治疗PSMA阳性mCRPC的上市申请。 “围猎”胃肠神经内分泌肿瘤神经内分泌肿瘤是一种罕见癌症，近年来发病率呈上升趋势。根据Frost & Sullivan数据，2020年我国胃肠胰腺神经内分泌瘤的新发确诊病例超7万例，且病例数还在逐年递增。胃肠胰神经内分泌肿瘤 (GEP-NETS) 起源于神经内分泌系统，可发生在胃肠道和胰腺的任何部位，由于许多患者无症状且确诊时已为转移性疾病的晚期，丧失手术切除机会，临床常用生长抑素类似物等药物疗法抑制肿瘤生长，但传统一线治疗药物如高剂量奥曲肽疗效有限。在此情况下，基于镥-177的肽受体放射性核素治疗（PRRT）类的RDC疗法以更优的临床表现被《CSCO神经内分泌肿瘤诊疗指南2021》列为推荐方案。目前针对该疾病已上市的RDC疗法仅有诺华的Lutathera（尚未在国内获批），该产品2024年全球净销售额达7.24亿美元，有望进击 “10亿美元俱乐部”。在Ⅲ期NETTER-1试验中，Lutathera组的客观影像学缓解率（ORR）为18%，奥曲肽LAR对照组为3%。在今年的ESMO上，赛诺菲与Orano Med联合开发的RDC药物AlphaMedix在针对GEP-NETs的一项Ⅱ期ALPHAMEDIX-02研究中达到全部主要疗效终点，展现出超越Lutathera的潜力。该研究包括两个队列，分别评估未接受过放射性配体（RLT）治疗 (n=35)和接受过RLT治疗(n=26)的GEP-NETs患者。研究者评估的结果显示，未经RLT治疗队列的患者使用AlphaMedix后，总缓解率（ORR）达到60.0%，疾病控制率（DCR）高达94.3%；而在既往接受过RLT治疗的患者中，ORR仍然达到了34.6%，疾病控制率为96.2%。初治患者在治疗24个月后，71.9%的患者仍然持续应答；36个月的疾病无进展生存率（PFS）为72.3%；36个月的总生存率（OS）达到88.2%。接受过RLT治疗的患者在治疗18个月后，全部患者仍然持续应答.18个月的PFS为82.6%；18个月的OS达到85.1%。（见下图）上下滑动查看来源|赛诺菲官网 AlphaMedix是一种采用铅-212同位素的靶向生长抑素受体（SSTR）、搭载α射线核素的RDC产品，相较于Lutathera和Pluvicto搭载的β射线辐射，α射线的射程更短、能量更高，理论上可以在精准杀伤肿瘤细胞的同时减少对周围正常组织的损伤。其于去年2月获得FDA突破性疗法认定。基于II期研究的积极结果，赛诺菲正在筹备一项国际多中心的III期临床试验。值得一提的是，当前多数治疗型RDC都是靶向PSMA/SSTR+搭载β射线核素，α射线核素日益凸显的疗效和安全性优势使得越来越多MNC开始逐渐转向开发这类产品，礼来、BMS和阿斯利康近两年达成的数十亿美元RDC相关交易都是涉及α射线核素的疗法。 ESMO上另一项针对GEP-NETs的Ⅲ期研究同样值得关注。德国ITM公司公布了其RDC药物ITM-11针对G1/G2级SSTR阳性GEP-NETs患者的Ⅲ期COMPETE试验数据。结果显示，与依维莫司相比，ITM-11的客观缓解率（ORR）中心评估达21.9%，局部评估提升至30.5%，显著高于依维莫司对照组（4.2%和8.4%），中位无进展生存期（mPFS）延长约1倍。且治疗中出现因不良事件而停药的发生率较低，耐受性显著高于对照组（1.8% vs 15.2%）。（见下图）来源|ITM官网基于该研究取得的临床成果，ITM计划在今年向FDA递交上市申请。 2021年12月，远大医药曾与ITM达成合作协议，获得了ITM-11在大中华区（中国大陆、香港、澳门、台湾）的开发、生产及商业化权益。今年3月，ITM-11针对GEP-NETs的国际多中心（包括中国）III期COMPOSE试验完成首例患者给药。这一试验将为 ITM-11在中国的上市奠定基础。同时，ITM-11还可与远大医药另一款用于诊断GEP-NETs的RDC产品ITM-14D形成产品组合，有望为GEP-NETs患者提供全新的诊疗一体化方案，覆盖GEP-NETs各阶段病程的诊疗需求。 ‌ 首个国产治疗用原研RDC临近上市在NETs这一复杂且异质性强的疾病领域，由于技术壁垒高、成本昂贵等原因，国内长期缺乏自主研发的PRRT药物。 ESMO年会上，先通医药自主研发的XTR008的III期XT-XTR008-3-01随机对照临床试验作为重磅研究以口头报告形式发布，中国NETs治疗迎来了曙光。该研究纳入了全国多个中心的患者，可更真实地反映中国GEP-NETs的疾病特征与治疗需求，未来有望在国内推动RDC治疗向一线挺进。这是国际上首个针对标准剂量的长效生长抑素类似物治疗失败的GEP-NETs开展的PRRT III期临床研究，也是中国第一个针对NET开展的PRRT的III期临床研究。旨在评估在G1/G2、分化良好的GEP-NETs患者中XTR008对比长效奥曲肽在无法手术或转移性GEP-NETs患者中的安全性及有效性。 ESMO上公布的最新数据显示，XTR008组的mPFS达到24.77个月，显著优于对照组的5.78个月（HR=0.14，95% CI: 0.090-0.219）。在肿瘤控制方面，XTR008组的ORR达到55.6%，DCR为94.9%，远优于对照组的2.1%和72.2%。在所有预设亚组中，XTR008单药治疗均表现出显著临床获益。总生存期（OS）数据尚不成熟，但已观察到获益趋势（HR=0.50）。（见下图）安全性方面，共计88.8%的患者完成了全部四个计划周期的治疗，显示XTR008单药治疗具有良好的安全性。值得一提的是，XTR008可同时实现“诊疗一体化”。XTR008在释放β射线杀伤肿瘤的同时，还可释放γ射线用于影像学监测，使医生可以实时观察药物在体内的分布。目前先通医药已向CDE 提交XTR008的上市申请，预计在明年可能获批，进而填补国内NETs靶向放射治疗的空白，比进口RDC更快惠及中国患者。编辑 | 姚嘉 yao.jia@PharmaDJ.com 总第2627期访问研发客网站，深度报道和每日新闻抢鲜看 www.PharmaDJ.com

临床3期临床失败临床终止

2025-10-25

·氨基观察

2025年ESMO，“核”势力的崛起

氨基观察-创新药组原创出品作者 | 沙晓威在医药圈，每年的ESMO大会就像一场“行业考试”，热门赛道的每一点动静都能引发关注。 2025年这场大会上，核药赛道依旧热度不减。既有诺华Pluvicto这样的明星药拓展新适应症，也有赛诺菲以α核素为基础的药物AlphaMedix刷新现有核药治疗记录。值得注意的是，中国企业带着首个国产核药PRRT药物站上国际舞台——先通制药的XTR008在神经内分泌瘤治疗上效果优异，且更符合中国患者的特征。此次ESMO大会的展示，也是核药崛起的一个缩影。从核素的选择、到递送方式，再到适应症的优化，核药的新一轮较量已经开始。 / 01 / Pluvicto：往更前线推进，忧喜参半提到核药，绕不开诺华的Pluvicto。作为第一款获批上市的核药，将这一“小众赛道”拉到了聚光灯下。 2024年狂揽14亿美元销售额，成为首个迈入重磅炸弹行列的放射性药物。但诺华显然不满足于此，PSMAfore试验的结果，帮助Pluvicto拓展了市场空间。2025年3月，FDA批准Pluvicto用于PSMA阳性的mCRPC患者化疗前的早期治疗，该审批将符合条件的患者数量增加了3倍。不过，Pluvicto的进击之路并未结束，今年ESMO上，它带着PSMAddition 3期试验数据，向激素敏感性前列腺癌（HSPC）这个更前线的适应症发起冲击。市场逻辑明确：Pluvicto目前获批的是mCRPC，人数较少。而HSPC患者处于疾病更早期阶段，患者人群庞大。诺华肿瘤学全球负责人Dushen Chetty更是直言，一旦该适应症获批，Pluvicto的合格患者群将直接翻倍，并大胆预测Pluvicto销售峰值将超过50亿美元。但现实却稍显冷静，这次ESMO大会上公布的PSMAddition数据可以说是“喜忧参半”。好消息是，Pluvicto联合SoC在放射学无进展生存期（rPFS）方面具有临床意义的改善，且与单独SoC相比，可将进展及死亡风险降低28%。延缓了HSPC进展为mCRPC的时间。坏消息是，关键的OS数据还没成熟，且HR是0.84。虽然Pluvicto组表现出积极趋势，但没有达到统计学意义上的显著差异。墨尔本Peter MacCallum癌症中心的肿瘤学家Arun Azad更是直接泼了冷水：“虽然PSMAddition中观察到的放射学无进展生存期益处可能会获得监管部门的批准，但即使进行更长时间的随访，也不可能看到OS益处。” 这样的担忧不是空穴来风。一方面是PSMAAddition出现了交叉病例的情况，即对照组中16%的患者后期转用了Pluvicto，这对OS的判断具有干扰性。另一方面，现阶段ADT联合ARPI的治疗手段虽疗效不及Pluvicto，但好在安全性更优。作为前列腺癌早期阶段，HSPC患者身体状态相对好，但Pluvicto的口干和胃肠道毒性，以及潜在恶性肿瘤的风险问题是否真的改善了患者生存质量仍需打个问号。尽管受到质疑，诺华仍是计划年底前根据最终的rPFS数据及更新后的OS结果，像FDA提交申请。此外，诺华还在积极筹备Pluvicto在寡转移前列腺癌患者的疗效（PSMA-DC），该适应症也是对疾病早期阶段的探索。在核药领域，诺华绝对是长期的领跑者：核心产品治疗前列腺癌的Pluvicto以及用于治疗GEP-NETs的Lutathera共同创造年净销售额超20亿的数据。除两款上市药物外，还有包括177Lu-NeoB、225Ac-PSMA-617在内的多款在研核药。2024年，公司还以17.5亿美元收购核药公司Mariana Oncology，继续加码。 / 02 / 新势力崛起 2025年ESMO，诺华的背后，是一众玩家在核药赛道的集体冒头。其中68Ga-OncoACP3-DOTA（诊断）和177Lu-OncoACP3-DOTA（治疗）的组合备受关注。2025年6月，Philochem AG以潜在总金额13.5亿美元的价格将药物授予BMS子公司RayzeBio。在治疗前列腺癌已有Pluvicto的背景下，这两款药物的优势在于靶向的酸性磷酸酶3（ACP3）相较于PSMA靶点更具肿瘤异质性，这一特性有效解决了PSMA低表达或不表达的治疗失效问题。此次大会公布的早期结果也符合预期，诊断性能优于PSMA，且治疗安全性更佳。 ITM公司的177Lu-edotreotide（ITM-11）则对标的是诺华的另一款药Lutathera，在治疗胃肠胰神经内分泌肿瘤（GEP-NETs）的3期COMPETE试验中同样表现出色，ORR达到21.9%，且全亚组实现mPFS延长。同样是针对GEP-NETs，赛诺菲的核药AlphaMedix（212Pb-DOTAMTATE）在缓解率上更是刷新了认知。此次EMSO大会上AlphaMedix针对GEP-NETs的Alphamedix-02试验结果进行了两次演示。首先是针对未经过放射治疗的患者，ORR为57%，效果上显著优于Lutathera。而针对既往接受过Lutathera治疗的患者，AlphaMedix的ORR达到19%，虽无差异化优势，但是具有临床意义。 AlphaMedix也代表新核药的迭代。作为一种基于α粒子的靶向疗法，AlphaMedix由用铅-212标记的生长抑素受体靶向肽复合物组成，可在患者体内产生α粒子攻击肿瘤。差异就在于此：α核素相较于Lutathera使用的β核素能量更高，能造成更频繁的双链DNA断裂，对肿瘤细胞杀伤更彻底，而且半衰期和电离半径短，对患者的毒副作用更小。目前FDA已授予AlphaMedix突破性疗法认定，用以治疗未接受过肽受体放射性疗法的GEP-NETs肿瘤患者。形成对比的是，同样基于铅-212的Perspective Therapeutics核药212Pb-VMT-α-NET的表现并不乐观。在未接受过核药治疗的NET患者的1/2期临床试验中，23例可评估患者的ORR为35%，在16名表达SSTR2患者（不同肿瘤）的亚组中，ORR为44%。但市场显然对这种“凑数”行为不满意，Perspective Therapeutics股价随之下跌。无论结局如何，此次ESMO已经展示了当前核药的研发热潮，而以新靶点、新核素、新适应症组成的新势力正在崛起。尽管还有许多药企并未在ESMO大会上展示，但是极具设计的思路也值得关注：比如，Cellectar Biosciences的磷脂药物偶联递送平台，能让核素穿过细胞膜精准送到肿瘤细胞。目前其管线Iopofosine I 131已经进入3期临床，针对的是多种实体瘤。 Oncoinvent则把目光放在了“冷门癌种”上。它用α核素镭-224开发的Radspherin，专门针对卵巢癌、结直肠癌的腹膜转移。这种转移灶位置隐蔽，传统治疗甚至免疫治疗也很难起效，但核药能通过放射性达到精准杀伤，目前已经进入2期临床。 / 03 / 中国力量没有缺席在2025年ESMO大会上，中国企业也有突破——先通医药公布了XTR008治疗GEP-NETs中国3期研究成果（XT-XTR008-3-01），同步登上了肿瘤学顶刊，拿到了国际顶级认证。临床结果显示：XTR008组的PFS达到24.77个月，疾病进展风险降低了86%（HR=0.14），ORR 55.6%（vs 2.1%），DCR更是高达94.9%（vs 72.2%）。所有患者亚组疗效一直，而且研究没有交叉设计，能够无偏移的评估XTR008的单药疗效。需要明确的是，该试验是完全基于中国患者数据做的试验。徐建明教授在ESMO大会点评时说：“XTR008的研究人群，比诺华之前的NETTER系列研究更符合中国NET特征。” 此次试验是全球首个针对“标准剂量长效生长抑素类似物治疗失败的GEP-NETs”开展的PRRT（肽受体放射性核素治疗）3期临床研究，也是中国第一个NET领域PRRT 3期研究。在ESMO官方媒体《ESMO Daily Reporter》针对NET的下一代放射性药物讨论中也出现了对XTR-008的积极评价：“令人鼓舞的疗效和非常轻微的毒性”。从临床需求上看，目前中国每年GEP-NETs新发患者不少，诺华的Lutathera并没有在中国获批，治疗手段很有限。今年4月XTR008的NDA已在受理，预计2026年就能获批，或将成为中国首个获批的靶向SSTR的治疗性放射性配体疗法。先通药业的表现也代表了中国药企在核药上的崛起。尽管如今以诺华、赛诺菲、BMS在内的MNCs在核药赛道进度领先，但国内包括中国同辐、东诚药业、纽瑞特医疗、远大医药、晶核生物在内的20多家药企也在竞逐。而先通药业管线更是构筑了10余款核药产品，多款药物已进入中后期临床试验。用于AD诊断的XTR005，已经在中国获批上市。当然核药赛道看着火热，想真正“跑起来”，没那么容易。除了早期的临床试验要过关，后期的生产以及临床应用，都是躲不开的问题。但已经明确的是，属于核药的“黄金时代”，开始了。 PS：欢迎扫描下方二维码，添加氨基君微信号交流。

临床3期

2025-10-20

·GlobeNewswire-Health Care

Press Release: ESMO: AlphaMedixTM phase 2 data support first-in-class potential of new targeted alpha therapy in gastroenteropancreatic neuroendocrine tumors

ESMO: AlphaMedixTM phase 2 data support first-in-class potential of new targeted alpha therapy in gastroenteropancreatic neuroendocrine tumors New AlphaMedix data showed sustained and clinically meaningful responses across both RLT-naïve and RLT-exposed patients with unresectable or metastatic GEP-NETs First phase 2 study to evaluate TAT with lead-212 supporting its potential to address high unmet medical needs in difficult-to-treat, rare cancersPhase 2 study met all primary efficacy endpoints and was presented across two oral presentations at the 2025 ESMO Congress in Berlin, Germany Paris, October 20, 2025. New data from the ALPHAMEDIX-02 phase 2 study (clinical study identifier: NCT05153772) evaluating AlphaMedix (212Pb-DOTAMTATE), an investigational somatostatin receptor (SSTR) targeted alpha therapy (TAT) using the lead-212 isotope, underscore the first-in-class potential of this investigational medicine for the treatment of patients with advanced gastroenteropancreatic neuroendocrine tumors (GEP-NETs). Detailed results from the phase 2 study, the first to evaluate a TAT across both radioligand therapy (RLT)-naïve and RLT-exposed patients affected by GEP-NETs, were presented in two oral presentations at the 2025 European Society for Medical Oncology (ESMO) Congress, Berlin, Germany. “Lead-212-based Targeted Alpha Therapy (TAT) could have a transformative impact across a broad range of solid tumors. With AlphaMedix’s consistent and clinically meaningful responses across both RLT-naïve and RLT-exposed gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients, the positive results underscore its potential in this rare and difficult-to-treat cancer,” said Volker Wagner, MD, PhD, Chief Medical Officer at Orano Med. “These data strongly encourage us to further advance the clinical development of AlphaMedix, and jointly with our partner, Sanofi, make this innovative TAT available to patients in need.” ALPHAMEDIX-02 phase 2 study ALPHAMEDIX-02 is a phase 2, open-label, multicenter study evaluating the efficacy and safety of AlphaMedix in patients with unresectable or metastatic SSTR+ GEP-NETs. The study included two cohorts evaluating RLT-naïve and RLT-exposed patients. The primary efficacy endpoint across both cohorts was the overall response rate (ORR). Secondary endpoints included progression-free survival (PFS) and overall survival (OS). The study's efficacy endpoints are based on local investigator assessment, per protocol. In addition, a blinded independent central review (BICR) was conducted subsequently. The key efficacy endpoints were met within both the investigator-assessed and BICR results. The following results were presented: RLT-Naïve(n=35) Investigator assessment Independent assessment (BICR) *DOR is determined only for participants who have achieved a confirmed complete response (CR) or partial response (PR) per RECIST 1.1**Defined as the percentage of patients achieving CR or PR or SD per RECIST 1.1***OS assessment is independent of RECIST 1.1 criteria, so BICR is n/a ORR 60.0%(95% CI: 42.1-76.1) 57.1%(95% CI: 39.4-73.7) Duration of Response (DoR) per Kaplan-Meier (KM) estimate (95% CI)* 71.9% for ≥ 24 months(95% CI: 44.6-87.4) 81.7% for ≥ 24 months(95% CI: 53.1-93.8) Complete Response (CR) - 2.9% Partial Response (PR) 60.0% 54.3% Stable Disease (SD) 34.3% 28.6% Disease control rate (DCR)** 94.3% (95% CI: 80.8-99.3) 85.7% (95% CI: 69.7-95.2) PFS 36-month PFS rate of 72.3% (95% CI: 53.3-84.5) 36-month PFS rate of 63.3% (95% CI: 40.3-79.4) OS 36-month OS rate of 88.2% (95% CI: 71.5-95.4) Not applicable*** RLT-Exposed(n=26) Investigator assessment Independent assessment (BICR) *DOR is determined only for participants who have achieved a confirmed complete response (CR) or partial response (PR) per RECIST 1.1**Defined as the percentage of patients achieving CR or PR or SD per RECIST 1.1***OS assessment is independent of RECIST 1.1 criteria, so BICR is n/a ORR 34.6%(95% CI: 17.2-55.7) 19.2%(95% CI: 6.6-39.4) Duration of Response (DoR) per Kaplan-Meier (KM) estimate (95% CI)* 100% for ≥ 18 months(95% CI: 100-100) 100% for ≥ 18 months(95% CI: 100-100) Partial Response (PR) 34.6% 19.2% Stable Disease (SD) 61.5% 80.8% Disease control rate (DCR)** 96.2%(95% CI: 80.4-99.9) 100%(95% CI: 86.8-100) PFS 18-month PFS rate of 82.6% (95% CI: 59.0-93.3) 18-month PFS rate of 88% (95% CI: 67.3-96.0) OS 18-month OS rate of 85.1% (95% CI: 58.5-95.2) Not applicable*** AlphaMedix™ had a similar safety profile across both cohorts. Within the RLT-naïve cohort, 85.7% of patients received all four doses of AlphaMedix, and 84.6% of patients within the RLT-exposed cohort. All GEP-NET patients experienced at least one treatment-emergent adverse event (TEAE). Grade ≥3 TEAEs occurred in 42.3% of RLT-exposed patients and 54.3% of RLT-naïve patients. The most common Grade ≥3 TEAEs in both groups was lymphocyte count decrease (25.7% of RLT-naïve patients and 15.4% of RLT-exposed patients). “The future of oncology research will be driven by cutting-edge science and next-generation modalities, such as radioligand therapies. AlphaMedix, a promising targeted alpha therapy, embodies the type of solution Sanofi is working to advance,” said Christopher Corsico, MD, Global Head of Development at Sanofi. “We are excited to share these robust scientific findings at ESMO as the data could represent a significant advancement in how we treat gastroenteropancreatic neuroendocrine tumors. As we engage with health authorities and advance the clinical program, we remain focused on bringing this innovative modality to patients who need new treatment options” Advancing AlphaMedix in GEP-NETsRLTs, which work by delivering radiation directly to tumor cells, represent an emerging area of oncology research. While current approved beta-emitting RLTs have improved outcomes in patients with GEP-NETs, there remains a critical gap in care, including in those who have progressed following previous RLT. TAT represents an innovative modality in RLT, harnessing high-energy, short-range alpha emissions to precisely target cancer cells while reducing potential exposure to surrounding tissue. "The results observed in the ALPHAMEDIX-02 trial clearly demonstrate exceptional levels of efficacy for a Targeted Alpha Therapy (TAT), based on current available therapies, in both radioligand therapy (RLT)-naïve and RLT-exposed populations and could potentially set new expectations when treating gastroenteropancreatic neuroendocrine tumor (GEP-NET) patients with RLTs” said Ebrahim Delpassand, MD, Founder and Chairman, CEO of RadioMedix. “For too long, this patient population has experienced inadequate disease control with current approved therapies. This important work provides hope for a new treatment for GEP-NET patients, their caregivers, and their healthcare providers.” In February 2024, AlphaMedix™ was designated as a breakthrough therapy by the US Food and Drug Administration in RLT-naïve patients with unresectable or metastatic GEP-NETs, recognizing the potential clinical benefits of lead-212–based TATs. The ALPHAMEDIX-02 results will form the basis for further discussions with health authorities. An international phase 3 study to further evaluate AlphaMedix in GEP-NETs is actively being planned. AlphaMedix is an investigational medicine and has not been approved by any regulatory authority. In September 2024, Sanofi entered an exclusive licensing agreement with Orano Med and RadioMedix to globally commercialize AlphaMedix. About the ALPHAMEDIX-02 studyALPHAMEDIX-02 is a phase 2, open-label, multicenter study evaluating the efficacy and safety of AlphaMedix (212Pb-DOTAMTATE) in patients with histologically confirmed unresectable or metastatic GEP-NETs, positive somatostatin analogue imaging and at least one site of measurable disease. The study included two cohorts evaluating RLT-naïve (n=35) and RLT-exposed (n=26) GEP-NET patients. RLT-exposed patients had progressive disease after receiving up to four doses of 177Lu-DOTATATE and received their last dose at least six months prior to Day 1. In both cohorts, AlphaMedix was administered at 67.6 μCi/kg every eight weeks for up to four cycles (6 mCi maximum per cycle). The primary efficacy endpoint across both cohorts was ORR per RECIST 1.1. Secondary endpoints included PFS and OS. About NETs NETs are a heterogeneous group of cancers that originate from neuroendocrine cells. These cancers occur mostly in the gastrointestinal tract and pancreas but can also occur in other tissues including the thymus, lung, and other uncommon sites such as the ovaries, heart, and prostate. Most NETs strongly express somatostatin receptors. Despite the global prevalence of NETs increasing each year, it is considered a rare cancer that is estimated to affect approximately 35/100,000 individuals worldwide. In the United States, around 12,000 patients annually are expected to be diagnosed with neuroendocrine tumors, with an average five-year survival rate of 60% at a metastatic stage. About Orano MedOrano Med is a subsidiary of the Orano Group. Orano Med is a clinical-stage biotechnology company that develops a new generation of targeted therapies against cancer using the unique properties of lead-212 (212Pb), an alpha-emitting radioisotope and one of the more potent therapeutic payloads against cancer cells known as Targeted Alpha Therapy (TAT). Leveraging its unique and secured access to 212Pb, the company is developing several 212Pb-based radioligand therapies combined with various targeting agents. Orano Med has 212Pb manufacturing facilities, laboratories, and R&D centers in France and in the US and is currently expanding its GMP-manufacturing capacities for 212Pb radiolabeled pharmaceuticals in North America and Europe. About RadioMedixRadioMedix, Inc., a clinical-stage biotechnology company and former sponsor of the AlphaMedix trial, is based in Houston and Humble, Texas. The company is focused on innovative targeted radiopharmaceuticals for diagnosis, monitoring, and therapy of cancer. RadioMedix is developing radiopharmaceuticals for PET imaging and therapy (alpha- and beta-labeled agents). The company established contract service facilities for academic and industrial partners. including a cGMP and analytical suite for Phase I-II-III clinical trials and commercial launch. To learn more, visit www.radiomedix.com and LinkedIn. About Sanofi Sanofi is an R&D driven, AI-powered biopharma company committed to improving people’s lives and delivering compelling growth. We apply our deep understanding of the immune system to invent medicines and vaccines that treat and protect millions of people around the world, with an innovative pipeline that could benefit millions more. Our team is guided by one purpose: we chase the miracles of science to improve people’s lives; this inspires us to drive progress and deliver positive impact for our people and the communities we serve, by addressing the most urgent healthcare, environmental, and societal challenges of our time. Sanofi is listed on EURONEXT: SAN and NASDAQ: SNY Media RelationsSandrine Guendoul | +33 6 25 09 14 25 | sandrine.guendoul@sanofi.com Evan Berland | +1 215 432 0234 | evan.berland@sanofi.com Léo Le Bourhis | +33 6 75 06 43 81 | leo.lebourhis@sanofi.com Victor Rouault | +33 6 70 93 71 40 | victor.rouault@sanofi.com Timothy Gilbert | +1 516 521 2929 | timothy.gilbert@sanofi.com Léa Ubaldi | +33 6 30 19 66 46 | lea.ubaldi@sanofi.com Investor RelationsThomas Kudsk Larsen | +44 7545 513 693 | thomas.larsen@sanofi.com Alizé Kaisserian | +33 6 47 04 12 11 | alize.kaisserian@sanofi.com Felix Lauscher | +1 908 612 7239 | felix.lauscher@sanofi.com Keita Browne | +1 781 249 1766 | keita.browne@sanofi.com Nathalie Pham | +33 7 85 93 30 17 | nathalie.pham@sanofi.com Tarik Elgoutni | +1 617 710 3587 | tarik.elgoutni@sanofi.com Thibaud Châtelet | +33 6 80 80 89 90 | thibaud.chatelet@sanofi.com Yun Li | +33 6 84 00 90 72 | yun.li3@sanofi.com Orano MedRegina Jehle | +33 6 74 56 11 31 | regina.jehle@orano.group Orano Press Office | +33 (0)1 34 96 12 15| press@orano.group Sanofi forward-looking statementsThis press release contains forward-looking statements as defined in the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements are statements that are not historical facts. These statements include projections and estimates and their underlying assumptions, statements regarding plans, objectives, intentions, and expectations with respect to future financial results, events, operations, services, product development and potential, and statements regarding future performance. Forward-looking statements are generally identified by the words “expects”, “anticipates”, “believes”, “intends”, “estimates”, “plans” and similar expressions. Although Sanofi’s management believes that the expectations reflected in such forward-looking statements are reasonable, investors are cautioned that forward-looking information and statements are subject to various risks and uncertainties, many of which are difficult to predict and generally beyond the control of Sanofi, that could cause actual results and developments to differ materially from those expressed in, or implied or projected by, the forward-looking information and statements. These risks and uncertainties include among other things, the uncertainties inherent in research and development, future clinical data and analysis, including post marketing, decisions by regulatory authorities, such as the FDA or the EMA, regarding whether and when to approve any drug, device or biological application that may be filed for any such product candidates as well as their decisions regarding labelling and other matters that could affect the availability or commercial potential of such product candidates, the fact that product candidates if approved may not be commercially successful, the future approval and commercial success of therapeutic alternatives, Sanofi’s ability to benefit from external growth opportunities, to complete related transactions and/or obtain regulatory clearances, risks associated with intellectual property and any related pending or future litigation and the ultimate outcome of such litigation, trends in exchange rates and prevailing interest rates, volatile economic and market conditions, cost containment initiatives and subsequent changes thereto, and the impact that global crises may have on us, our customers, suppliers, vendors, and other business partners, and the financial condition of any one of them, as well as on our employees and on the global economy as a whole. The risks and uncertainties also include the uncertainties discussed or identified in the public filings with the SEC and the AMF made by Sanofi, including those listed under “Risk Factors” and “Cautionary Statement Regarding Forward-Looking Statements” in Sanofi’s annual report on Form 20-F for the year ended December 31, 2024. Other than as required by applicable law, Sanofi does not undertake any obligation to update or revise any forward-looking information or statements. All trademarks mentioned in this press release are the property of the Sanofi group with the exception of Orano Med and AlphaMedix™. Attachment Press_Release

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适应症	最高研发状态	国家/地区	公司	日期
生长抑素受体阳性神经内分泌肿瘤	临床2期	美国	Orano Med LLC	2021-12-21
神经内分泌肿瘤	临床2期	美国	RadioMedix, Inc.	2021-12-01

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临床结果

适应症

分期

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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


NCT05153772 (ALPHAMEDIX 02, ESMO2025)	临床2期	胃肠胰神经内分泌肿瘤	26	212Pb-DOTAMTATE	繭築鏇鑰餘簾醖憲簾淵(糧憲醖簾蓋窪觸壓夢獵) = 網膚壓餘襯網築簾窪願簾鹹襯鏇襯廠鬱願製艱 (製憲觸淵醖構鬱遞鹽鬱 ) 更多	积极	2025-10-17
NCT05153772 (ALPHAMEDIX 02, ESMO2025)	临床2期	胃肠胰神经内分泌肿瘤 SSTR+	1,034	212Pb-DOTAMTATE	夢構蓋蓋蓋齋鏇網網膚(築艱選鬱積製糧積鏇淵) = 膚膚窪壓餘廠夢網醖構觸襯簾選構製蓋築選窪 (鑰壓獵範蓋簾憲憲製簾, 39.4 ~ 73.7) 更多	积极	2025-10-17
NCT05153772 (ALPHAMEDIX 02, Company_Website) 人工标引	临床2期	胃肠胰神经内分泌肿瘤 Somatostatin Receptor Positive	-	AlphaMedix (PRRT‑naïve)	鹽網廠鬱製衊鹽壓獵選(願淵築襯壓鬱淵獵衊糧) = AlphaMedix met all primary efficacy endpoints and showed clinically meaningful overall response rates. 鬱築壓遞鏇獵鏇製鑰艱 (遞憲築鑰襯窪積夢繭鏇 ) 达到更多	积极	2025-10-08
NCT05153772 (ALPHAMEDIX 02, Company_Website) 人工标引	临床2期	胃肠胰神经内分泌肿瘤 Somatostatin Receptor Positive	-	AlphaMedix (PRRT‑exposed)		积极	2025-10-08
NCT05153772 (ALPHAMEDIX 02, ASCO2024)	临床2期	胃肠胰神经内分泌肿瘤 SSTR+	-	212Pb-DOTAMTATE	構鑰網窪鑰鑰繭膚壓廠(糧製鬱淵鹽鏇醖齋製鹽) = 糧鏇遞顧鬱淵糧遞鏇繭選醖齋鹽製醖艱網餘膚 (夢簾鏇膚餘衊艱觸鹹廠, 32.0 ~ 63.0)	积极	2024-05-24
NCT05153772 (ALPHAMEDIX 02, ASCO2024)	临床2期	胃肠胰神经内分泌肿瘤 SSTR+	-	177Lu-DOTATATE	構鑰網窪鑰鑰繭膚壓廠(糧製鬱淵鹽鏇醖齋製鹽) = 鏇遞蓋積醖蓋窪醖鏇醖選醖齋鹽製醖艱網餘膚 (夢簾鏇膚餘衊艱觸鹹廠, 10 ~ 25)	积极	2024-05-24
212Pb-DOTAMTATE (SNMMI2022)	N/A	神经内分泌肿瘤 SSTR expressing	11	212Pb-DOTAMTATE at 67.6 µCi/kg/cycle	憲鹹壓製齋觸窪蓋遞壓(襯網選鹹遞鑰鹹壓襯窪) = 願獵齋淵鬱觸遞襯觸衊遞範顧衊鬱顧糧觸衊顧 (蓋網簾鬱憲範積顧鏇鑰 )	积极	2022-08-08
NCT03466216 (ASCO2022) 人工标引	临床1期	神经内分泌肿瘤	10	212Pb-DOTAMTATE	襯艱製蓋壓壓繭憲繭網(網獵觸壓淵簾醖選襯網) = 窪選鑰遞衊糧襯積願繭憲淵淵選鑰衊製醖範壓 (襯艱淵壓膚糧築壓顧製 ) 更多	积极	2022-06-02
NCT03466216 (ASCO 12021 \| ASCO 22021) 人工标引	临床1期	神经内分泌肿瘤一线 SSTR Expression	20	AlphaMedix	衊築廠艱襯鏇齋顧觸壓(壓醖憲網觸鑰顧鏇鬱壓) = 遞鏇膚製積憲選鏇膚醖鹹網構鹹鹽觸鹽選壓積 (窪憲夢糧餘鏇顧糧顧構 ) 更多	积极	2021-05-20
AlphaMedix (EANM2020)	N/A	神经内分泌肿瘤 SSTR-	16	AlphaMedix 30.7 ÂµCi/kg	製艱鹹廠鑰膚鹹製衊顧(艱憲遞鹽憲構艱憲膚衊) = 7/16 (43%) 積膚鬱製鑰築淵鹹醖簾 (糧觸憲衊獵齋醖鹽獵鹽 ) 更多	积极	2020-09-18
AlphaMedix (EANM2020)	N/A	神经内分泌肿瘤 SSTR-	16	AlphaMedix 40.0 ÂµCi/kg		积极	2020-09-18
AACR2020	N/A	神经内分泌肿瘤	13	AlphaMedixTM	醖鏇鹹鏇夢製繭鹹糧餘(糧鹹構憲簾獵鹹膚觸選) = No clinically significant investigational drug-related hematological and renal toxicity was noted. 選蓋鬱網夢繭醖觸窪鹽 (遞願襯壓衊鹽廠製窪鑰 ) 更多	积极	2020-08-15