A Multicenter, Randomized, Controlled Phase 2 Study: Efficacy and Safety of I-131-1095 Radiotherapy in Combination With Enzalutamide in mCRPC Patients Who Are 18F-DCFPyL PSMA-avid, Chemotherapy-naïve, and Progressed on Abiraterone (ARROW )

This clinical trial was done to show whether a radioactive drug (I-131-1095) that binds to prostate-specific membrane antigen (PSMA) is useful in treating metastatic prostate cancer that is positive for PSMA. The trial enrolled men whose PSMA-positive metastatic prostate cancer had progressed while they were taking abiraterone. During the trial, all of the men took enzalutamide (standard-of-care therapy) once a day. However, some of the men also had up to 4 doses (8 weeks apart) of I-131-1095 (in addition to taking enzalutamide once a day). At specified times during the trial, all of the men had blood tests (to measure levels of prostate-specific antigen [PSA]) and imaging studies (to assess tumor status). The two groups of men were then compared in several ways. The main comparison was the percentage of men in each group with at least a 50% decrease in PSA levels. Other comparisons involved the response of the tumors (as seen on imaging) and overall survival. To assess safety, the number of adverse events in both groups were also compared.

开始日期2019-05-30

申办/合作机构

Progenics Pharmaceuticals, Inc.

NCT03030885

/ Completed临床1期IIT

A Phase 1, Open-Label, Dose Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095 for the Treatment of Metastatic Castration-Resistant Prostate Cancer (mCRPC)

The main purpose of this study to determine the safety of an experimental medicine called 131I-MIP-1095. 131I-MIP-1095 is an investigational drug, meaning it has not been approved by the U.S. Food & Drug Administration (FDA).

开始日期2017-01-19

申办/合作机构

Memorial Sloan Kettering Cancer Center

[+1]

NCT00712829

/ Completed临床1期

A Phase I Study Evaluating the Safety, Pharmacokinetics, Tissue Distribution, Metabolism of Small Molecule Inhibitors of Prostate Specific Membrane Antigen: Determination of I-123 Radiation Dosimetry for 123-I-MIP-1072 and 123-I-MIP-1095

This is a single blinded, randomized, cross-over design. Up to 12 patients will be randomly administered a single 10.0 mCi dose of 123I-MIP-1072 or 123I-MIP-1095 (study drugs). The second (alternate) study drug will be administered approximately 14 days after the first. A final follow-up visit will occur approximately 2 weeks after the injection of the alternate study drug.

开始日期2008-05-01

申办/合作机构

Molecular Insight Pharmaceuticals, Inc.

100 项与 131I-MIP-1095 相关的临床结果

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100 项与 131I-MIP-1095 相关的转化医学

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100 项与 131I-MIP-1095 相关的专利（医药）

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项与 131I-MIP-1095 相关的文献（医药）

2024-08-01·NUCLEAR MEDICINE COMMUNICATIONS

A phase 2, single-arm trial evaluating 131I-PSMA-1095 targeted radioligand therapy for metastatic castration-resistant prostate cancer

Article

作者: Fallah, Parvaneh ; Labidi, Soumaya ; Mamo, Aline ; Rose, April A.N. ; Probst, Stephan M. ; Liu, Richard F. ; Ferrario, Cristiano

Background:

Metastatic castration-resistant prostate cancer (mCRPC) remains uniformly lethal. Prostate specific membrane antigen (PSMA) is a transmembrane glycoprotein overexpressed in prostate cancer. 131I-PSMA-1095 (also known as 131I-MIP-1095) is a PSMA-targeted radioligand which selectively delivers therapeutic radiation to cancer cells and the tumor microenvironment.

Methods:

We conducted a single-arm, phase 2 trial to assess efficacy and tolerability of 131I-PSMA-1095 in mCRPC patients who had exhausted all lines of approved therapy. All patients underwent 18F-DCFPyL PET and 18F-FDG PET to determine PSMA-positive tumor volume, and patients with >50% PSMA-positive tumor volume were treated with up to four doses of 131I-PSMA-1095. The primary endpoint was the response rate of prostate specific antigen (PSA). Secondary endpoints included rates of radiographic response and adverse events. Overall and radiographic progression-free survival were also analyzed.

Results:

Eleven patients were screened for inclusion and nine patients received 131I-PSMA-1095. The median baseline PSA was 162 µg/l, and six patients demonstrated a >50% PSA decrease. One patient demonstrated a confirmed radiographic response. Median overall survival was 10.3 months, and median progression-free survival was 5.4 months. Four patients experienced adverse events of grade 3 or higher, the most frequent being thrombocytopenia and anemia.

Conclusion:

131I-PSMA-1095 is highly active against heavily-pretreated PSMA-positive mCRPC, significantly decreasing tumor burden as measured by PSA. Adverse events, mainly hematologic toxicity, were not infrequent, likely related to off-target irradiation. This hematologic toxicity, as well as a higher logistical burden associated with use, could represent relative disadvantages of 131I-PSMA-1095 compared to 177Lu-PSMA-617.

2023-11-01·Clinical nuclear medicine

A Phase 1, Open-label, Dose-Ascending Study to Evaluate the Safety and Tolerability of the Therapeutic Radiopharmaceutical 131I-MIP-1095 for the Treatment of Metastatic Castration-Resistant Prostate Cancer

Article

作者: Laccetti, Andrew L. ; Bodei, Lisa ; Weber, Wolfgang A. ; Morris, Michael J. ; O'Donoghue, Joseph A.

Purpose:

131I-MIP-1095 is a targeted radiotherapeutic that contains 131I, a β-particle emitter, and MIP-1095, a urea-based ligand for prostate-specific membrane antigen. We report the first phase 1, dose-escalation study of 131I-MIP-1095 in patients with metastatic castration-resistant prostate cancer (mCRPC).

Methods:

This study enrolled men with mCRPC refractory to second-generation antiandrogen(s) and taxane chemotherapy. Dosimetry/biodistribution assessments were performed. Safety and tolerability were determined in subjects who qualified for therapeutic administration of 131I-MIP-1095 with maximum tolerated activity examined in a dose-ascending manner (3 + 3 design methodology). Disease outcomes including prostate-specific antigen (PSA) change, tumor response, survival, and circulating tumor cell concentration were assessed.

Results:

A total of 9 subjects with mCRPC were included in this study. On the basis of dosimetry results, 5 of 9 patients were treated: 3 in cohort 1 (50 mCi) and 2 in cohort 2 (75 mCi). Accrual stopped at the cohort 2 activity level in response to the US Food and Drug Administration mandate for 131I-MIP-1095 manufacturing concerns. Parotid/salivary glands (3.5 Gy/Bq), liver (2.2 Gy/Bq), kidneys (1.3 Gy/Bq), and spleen (0.7 Gy/Bq) demonstrated the greatest extent of 131I-MIP-1095 exposure. There were no deaths, serious adverse events, or drug discontinuations due to treatment-emergent adverse events. Grade 1–2 thrombocytopenia, anemia, leukopenia, and dry mouth most commonly occurred. One subject (33.3%) exhibited maximum decline for the PSA response of 50% or greater.

Conclusion:

131I-MIP-1095 demonstrated favorable dosimetry, biodistribution, and safety, as well as a modest PSA response supporting further investigation for treatment of men with mCRPC.Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03030885, Registered January 25, 2017 (https://clinicaltrials.gov/ct2/show/NCT03030885).

2020-03-01·Bioorganic & medicinal chemistry

Synthesis and evaluation of novel radioiodinated PSMA targeting ligands for potential radiotherapy of prostate cancer

Article

作者: Seok Rye Choi ; David Alexoff ; Lin Zhu ; Hank F. Kung ; Zhihao Zha ; Karl Ploessl ; Xinyue Yao ; Ruiyue Zhao

Radioligand therapy (RLT) using prostate-specific membrane antigen (PSMA) targeting ligands is an attractive option for the treatment of Prostate cancer (PCa) and its metastases. We report herein a series of radioiodinated glutamate-urea-lysine-phenylalanine derivatives as new PSMA ligands in which l-tyrosine and l-glutamic acid moieties were added to increase hydrophilicity concomitant with improvement of in vivo targeting properties. Compounds 8, 15, 19a/19b and 23a/23b were synthesized and radiolabeled with ¹²⁵I by iododestannylation. All iodinated compounds displayed high binding affinities toward PSMA (IC₅₀ = 1-13 nM). In vitro cell uptake studies demonstrated that compounds containing an l-tyrosine linker moiety (8, 15 and 19a/19b) showed higher internalization than MIP-1095 and 23a/23b, both without the l-tyrosine linker moiety. Biodistribution studies in mice bearing PC3-PIP and PC3 xenografts showed that [¹²⁵I]8 and [¹²⁵I]15 with higher lipophilicity exhibited higher nonspecific accumulations in the liver and intestinal tract, whereas [¹²⁵I]19a/19b and [¹²⁵I]23a/23b containing additional glutamic acid moieties showed higher accumulations in the kidney and implanted PC3-PIP (PSMA+) tumors. [¹²⁵I]23b displayed a promising biodistribution profile with favorable tumor retention, fast clearance from the kidney, and 2-3-fold lower uptake in the liver and blood than that observed for [¹²⁵I]MIP-1095. [^125/131I]23b may serve as an optimal PSMA ligand for radiotherapy treatment of prostate cancer over-expressing PSMA.

项与 131I-MIP-1095 相关的新闻（医药）

2026-03-25

·核联盛

从概念到获批：诊疗核药的破局之路 ——FDA 审批底层逻辑与前列腺癌实战真经

原文：From Concept to Regulatory Drug Approval: Lessons for Theranostics Marlon Perera1 and Michael J. Morris2 1Urology Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, New York; and 2Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York 摘要放射性药物治疗是新兴肿瘤治疗手段，在肿瘤综合治疗中的重要性日益凸显。前列腺癌（PCa）是最常见的实体肿瘤之一，给社会带来沉重负担。尽管前列腺癌具有高度异质性，但因其病程长、易发生转移、对放疗敏感，成为放射性药物治疗的理想靶点。截至目前，晚期前列腺癌领域是放射性药物研发与获批最成功的方向之一。本文总结新型药物获得监管审批所需的复杂流程，重点说明放射性药物审批特有的局限与障碍；以晚期前列腺癌为例，依据前列腺癌临床试验工作组（PCWG）建议，阐述试验设计中疾病状态界定与合理终点指标选择的重要性；最后结合FDA审批原则与PCWG框架，梳理²²³镭与¹⁷⁷镥- PSMA-617两款放射性药物的成功获批经验。一、放射性药物的核心本质与临床价值放射性药物治疗是分子靶向与放射治疗深度融合的肿瘤治疗新范式，并非传统放疗的简单延伸。其结构由靶向配体与放射性核素两部分组成，前者负责精准递送，后者通过释放α/β 粒子造成肿瘤细胞 DNA 不可逆损伤，实现系统性、高特异性的辐射杀伤。 β 发射体（¹⁷⁷Lu、⁹⁰Y、¹³¹I）射程中等、覆盖范围广，适合连片清除病灶；α 发射体（²²³Ra、²¹²Bi）射程极短、能量密度极高，杀伤效力更强且对正常组织保护更优。与外照射相比，放射性药物可全身给药、覆盖广泛转移灶，配合伴随诊断成像实现获益人群筛选、药物分布评估与疗效监测的全流程可视化，使其成为骨转移高发、病灶弥散的前列腺癌的理想治疗选择。二、FDA 创新药审批全流程：核心框架与关键节点 FDA 对放射性药物的监管围绕安全性与临床有效性两大核心构建，是全球最严格的药品上市体系，全程分为三个不可逾越的核心阶段。图 1：Overview of FDA process for new drug approval 2.1 研究性新药申请（IND）：临床试验入场券药物进入人体研究前，必须提交IND 申请，完整提交临床前药理毒理、生产工艺、质量控制及试验方案，缺一不可。 2.2 临床试验阶段：分阶验证与证据积累Ⅰ期：评估安全性、耐受性与剂量，放射性药物可豁免正式Ⅰ期，依托成熟安全性数据直接进入Ⅱ期；Ⅱ期：在目标患者中初步验证疗效信号，完善风险数据；Ⅲ期：大样本随机对照试验，以硬临床终点确证获益，是获批的核心依据。 2.3 新药申请（NDA）：最终上市审批完成Ⅲ期后提交NDA，汇总全链条数据；针对未满足临床需求的药物，可申请快速通道、突破性疗法、加速批准、优先审评，大幅压缩审批时间。从概念到获批，常规药物耗时10–15 年、成本达数十亿美元，放射性药物因跨领域属性，难度与成本进一步提升。三、放射性药物研发与审批的特有壁垒放射性药物的困境并非技术短板，而是体系性、工程性、监管性三重约束叠加的结果。学科协同壁垒：肿瘤内科管患者、核医学管给药，跨专业协作断裂直接拖慢研发；资源与资质硬约束：核素半衰期短、需现场制备，辐射防护要求高，放射化学 / 药学专业人才长期短缺；全球监管碎片化：部分地区监管宽松，同情用药普遍存在，研发方缺乏开展规范试验、积累监管认可数据的动力。四、前列腺癌药物审批的核心困境与破局框架前列腺癌是放射性药物获批最集中的领域，同时面临疾病特性与评价体系不匹配的尖锐矛盾。 4.1 四大核心审批障碍疾病高度异质性，生存终点难以统一；老年患者为主，竞争死亡风险干扰结果判断；骨转移为主，传统 RECIST 标准无法准确评估疗效；PSA、PSMA 均未被 FDA 认可为临床获益替代终点。 4.2 破局关键：PCWG 评价体系前列腺癌临床试验工作组（PCWG）通过 PCWG1/2/3 共识，建立了统一、可监管、可重复的试验框架，最核心突破是确立rPFS（影像学无进展生存期）为总生存替代终点，并提出 “2+2” 判效规则，有效解决骨转移疗效评估难题，rPFS 与总生存相关系数高达0.72。五、两大里程碑药物：获批逻辑与关键证据基于FDA 规则与PCWG 框架，²²³Ra‑二氯化物与¹⁷⁷Lu‑PSMA‑617先后获批，成为前列腺癌核药的标杆。试验名称临床试验.gov 编号分期样本量 (n) 治疗方案研究地区高危局限性 / 寡转移性前列腺癌切除术 NCT04430192 Ⅱ期 20 前列腺癌术前使用 ¹⁷⁷Lu-PSMA-617 澳大利亚 BullsEye NCT04443062 Ⅱ期 58 ¹⁷⁷Lu-PSMA-617 vs 标准治疗荷兰 PROQURE-1 NCT05162573 Ⅰ期 18 体外放疗 +¹⁷⁷Lu-PSMA-617 荷兰转移性去势抵抗性前列腺癌前线紫杉类化疗 NCT04343885 Ⅱ期 140 紫杉类化疗 +¹⁷⁷Lu-PSMA-617 澳大利亚 ProstACT TARGET NCT05146973 Ⅱ期 50 体外放疗 +¹⁷⁷Lu-DOTA-TLX591 澳大利亚 PSMAddition NCT04720157 Ⅰ期 1,126 标准治疗 +¹⁷⁷Lu-PSMA-617 美国、韩国、新加坡、中国台湾 - NCT04206319 Ⅱ期 26 ¹⁷⁷Lu-PSMA-617 美国 - NCT053079698 Ⅰ期 6 ¹⁷⁷Lu-PSMA-617 + 立体定向放疗美国转移性去势抵抗性前列腺癌一线治疗 NCT04419402 Ⅱ期 160 恩扎卢胺 +¹⁷⁷Lu-PSMA-617 澳大利亚 PSMAfore NCT04689828 Ⅲ期 450 ¹⁷⁷Lu-PSMA-617 vs 雄激素受体通路抑制剂标准治疗北美、欧洲转移性去势抵抗性前列腺癌二线治疗 NCT03874884 Ⅰ期 52 ¹⁷⁷Lu-PSMA-617 + 奥拉帕利澳大利亚 PRINCE NCT03658477 Ⅱ期 37 ¹⁷⁷Lu-PSMA-617 + 帕博利珠单抗澳大利亚 - NCT03805594 Ⅰ期 43 ¹⁷⁷Lu-PSMA-617 + 帕博利珠单抗美国 - NCT04946370 Ⅱ期 41 ¹⁷⁷Lu-PSMA-617 + 帕博利珠单抗美国 - NCT04647526 Ⅱ期 415 ¹⁷⁷Lu-PSMA-617 + 帕博利珠单抗 vs 雄激素受体通路抑制剂二线治疗北美、欧洲 - NCT047056587 Ⅱ期 105 ²²⁵Ac-J591 美国 ARROW NCT03938669 Ⅱ期 70 恩扎卢胺 + MIP 1095 北美 - NCT04644770 Ⅱ期 70 ²²⁵Ac-h11B6 美国 SECuRE NCT04686604 Ⅱ期 44 ⁶⁴Cu-SAR-bisPSMA 美国 LuCAB NCT05340374 Ⅱ期 47 ¹⁷⁷Lu-PSMA-617 + 卡巴他赛澳大利亚 - NCT04071236 Ⅱ期 24 ²²⁵Ra+M3814 美国 TATCIST NCT05219500 Ⅱ期 11 ²²⁵Ac-PSMA-I&T 美国 - NCT04886986 Ⅱ期 33 ²²⁵Ac+¹⁷⁷Lu-PSMA-617 美国 ECLIPSE NCT05208297 Ⅱ期 400 ¹⁷⁷Lu-PSMA-617 + 阿维鲁单抗美国 - NCT04974111 Ⅱ期 31 ²²⁵Ac-PSMA-617 美国 PROSTACT NCT04876651 Ⅲ期 387 ¹⁷⁷Lu-J591 表 1：Comparison of ²²³Ra and ¹⁷⁷Lu‑PSMA‑617 Phase III Trial Designs 5.1 ²²³Ra‑二氯化物：α 核素骨靶向的开山之作作为α 发射体，²²³Ra 模拟钙掺入骨转移区域，靶向骨微环境实现局部杀伤。其获批核心依据为Ⅲ期 ALSYMPCA 试验：922 例骨转移mCRPC患者，治疗组中位 OS 14.0 个月，显著优于对照组11.2 个月，症状性骨骼事件显著延迟。重要警示：与阿比特龙联用会增加骨折与死亡风险，联合用药需严格评估安全性。 5.2 ¹⁷⁷Lu‑PSMA‑617：诊疗一体化的巅峰范式 PSMA 在前列腺癌细胞中表达上调 1000 倍，是极致精准的靶点；治疗前必须经PSMA‑PET筛选阳性人群，杜绝无效治疗。其获批依托Ⅲ期 VISION 试验，采用rPFS+OS 双主要终点，两项终点均显著达标：rPFS 从 3.4 个月延长至 8.7 个月，OS 从 11.3 个月延长至 15.3 个月，成为全球首个获批的PSMA 靶向放射配体治疗药物。六、前列腺癌放射性药物的未来发展方向图 2：Trials assessing ¹⁷⁷Lu‑PSMA‑617 therapy in various stages of PCa 插入表2：Current Radiopharmaceutical Trials in PCa 审查类型 ALSYMPCA (43) VISION (57) 治疗药物 ²²³Ra ¹⁷⁷Lu-PSMA-617 入组患者标准去势抵抗性前列腺癌（CRPC）进展；骨扫描证实≥2 处骨转移，无内脏转移；既往多西他赛或多西他赛类化疗不耐受转移性去势抵抗性前列腺癌（CRPC）进展；PSMA-PET 证实 PSMA 阳性；既往接受过≥1 种雄激素受体抑制剂治疗；既往接受紫杉类化疗（1 或 2 种方案）治疗组方案 ²²³Ra（50 kBq/kg），每 4 周给药 1 次，最多 6 剂 ¹⁷⁷Lu-PSMA-617（7.4 GBq），每 6 周为 1 个周期，最多 4 个周期对照组方案标准治疗：如抗雄激素药物（禁止联用化疗、体外放疗、系统性放射性核素）标准治疗：如抗雄激素药物（禁止联用化疗、体外放疗、系统性放射性核素、免疫治疗）主要终点总生存期总生存期；影像学无进展生存期（rPFS）次要终点碱性磷酸酶（ALP）变化（升高时间、ALP 缓解情况）；前列腺特异性抗原（PSA）升高时间；首次症状性骨骼事件发生时间（首次体外放疗用于骨骼症状、病理性骨折、脊髓压迫或肿瘤相关骨科干预时间）客观缓解率、疾病控制率（RECIST 标准）；首次症状性骨骼事件发生时间（首次体外放疗用于骨骼症状、病理性骨折、脊髓压迫或肿瘤相关骨科干预时间） FDA 获批适应症伴症状性骨转移、无内脏转移的去势抵抗性前列腺癌（CRPC）既往接受雄激素受体通路抑制及紫杉类化疗的 PSMA 阳性转移性去势抵抗性前列腺癌（CRPC）未来研发将沿三条主线推进：治疗时机前移：从晚期 mCRPC 向局限期、高危前线推进，用替代终点缩短试验周期；联合策略优化：探索核药与免疫、PARP 抑制剂、内分泌治疗的协同，严控联合风险；技术迭代升级：高活性 α 核素（²²⁵Ac、²¹¹At）、新靶点药物持续突破，提升疗效与安全性。同时，全球监管协同与标准化试验设计，是提升研发效率、加速上市的核心抓手。七、总结：核药获批的底层逻辑与范式启示放射性药物的 FDA 获批，不是流程通关，而是疾病机制、药物特性、试验设计、监管规则高度耦合的系统工程。前列腺癌的两次突破，验证了诊疗一体化模式的不可替代价值，也建立了可复制、可推广的研发路径。随着靶点优化、核素迭代、试验设计成熟与全球监管统一，放射性药物将从晚期挽救治疗走向前线标准治疗，深刻改变前列腺癌乃至泛肿瘤领域的精准治疗格局。声明本文为作者基于公开文献、公开报道及行业资料整理形成的观点性内容，仅用于学术与产业交流。文中若涉及相关研究团队、机构或个人成果，如存在引用不当、理解偏差或可能影响相关权益的情况，欢迎及时联系作者，我们将第一时间核实并做出修订或删除处理

放射疗法临床3期临床申请

2024-10-10

·PRNewswire

Metastatic Castration-Resistant Prostate Cancer Clinical Trial Pipeline Appears Robust With 90+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Metastatic Castration-Resistant Prostate Cancer (mCRPC) refers to prostate cancer that has spread (metastasized) to other parts of the body and continues to progress despite treatments that lower testosterone levels (androgen deprivation therapy or ADT) major pharmaceutical companies are heavily investing in research and development of new treatments, including immunotherapy (e.g., sipuleucel-T) and targeted therapies, which are seen as the next frontier in treating mCRPC. The use of precision medicine to identify genetic profiles in patients has further expanded the potential for targeted treatment. LAS VEGAS , Oct. 10, 2024 /PRNewswire/ -- DelveInsight's ' Metastatic Castration-Resistant Prostate Cancer Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline mCRPC therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the mCRPC pipeline domain. Key Takeaways from the Metastatic Castration-Resistant Prostate Cancer Pipeline Report DelveInsight's mCRPC pipeline report depicts a robust space with 90+ active players working to develop 100+ pipeline therapies for mCRPC treatment. Key mCRPC companies such as Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others are evaluating new mCRPC drugs to improve the treatment landscape. Promising mCRPC pipeline therapies such as REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others are under different phases of mCRPC clinical trials. In October 2024, Curium announced that it had entered into a strategic partnership with PDRadiopharma Inc, a wholly-owned subsidiary of PeptiDream, for the clinical development, regulatory filing, and commercialization in Japan of 177Lu-PSMA-I&T and 64Cu-PSMA-I&T. The two agents 177Lu-PSMA-I&T and 64Cu-PSMA-I&T target prostate-specific membrane antigen (PSMA) expressed on prostate cancer cells and are being investigated for prostate cancer treatment and diagnostics. In July 2024, the US FDA granted fast-track designation to the prostate-specific membrane antigen (PSMA)–targeted radiopharmaceutical 225Ac-FL-020 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC). In July 2024, Merck and Orion Corporation announced the mutual exercise of option providing Merck global exclusive rights to Opevesostat, an investigational CYP11A1 inhibitor, for the treatment of Metastatic Castration-Resistant Prostate Cancer. In July 2024, the US FDA granted fast-track designation to the antibody-drug conjugate (ADC) BNT324/DB-1311 to potentially treat patients with unresectable advanced or metastatic castration-resistant prostate cancer (mCRPC) whose disease had progressed on or after standard systemic regimens. In July 2024, FutureChem announced that the FC-705 has received orphan drug designation from the Ministry of Food and Drug Safety (MFDS) for the treatment of prostate cancer. In June 2024, CAR T-Cell Therapy demonstrated promising results for mCRPC according to Phase I trial results. In January 2024, Lava Therapeutics announced that it has signed a clinical trial collaboration and supply agreement with Merck to evaluate its prostate cancer therapy LAVA-1207 as a combination treatment with MSD's Keytruda (pembrolizumab). In July 2024, Blue Earth Therapeutics announced the signing of a clinical research collaboration with University College London (UCL). The collaboration is centered on a Phase I/II trial designed to evaluate the safety, tolerability, radiation dosimetry, and antitumor activity of the 225Ac-rhPSMA-10.1 in men with metastatic castrate-resistant prostate cancer who have previously responded to lutetium 177 (177Lu)-PSMA therapy. Request a sample and discover the recent advances in mCRPC treatment drugs @ Metastatic Castration-Resistant Prostate Cancer Pipeline Report The mCRPC pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage mCRPC drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the mCRPC clinical trial landscape. Metastatic Castration-Resistant Prostate Cancer Overview Metastatic castration-resistant prostate cancer (mCRPC) is an advanced stage of prostate cancer that continues to grow and spread despite hormone therapy aimed at lowering testosterone levels. The term "metastatic" refers to cancer spreading to other parts of the body, such as the bones, lymph nodes, or distant organs, while "castration-resistant" indicates that the cancer no longer responds to treatments that reduce testosterone, a key driver of prostate cancer growth. mCRPC is typically more aggressive and challenging to treat than earlier stages of prostate cancer. The causes of mCRPC stem from genetic and environmental factors. Genetic mutations in the androgen receptor pathway can make cancer cells less dependent on testosterone, allowing them to thrive even under hormone-suppressing treatments. Environmental factors like diet, lifestyle, and exposure to certain chemicals may also contribute to the development and progression of prostate cancer. Symptoms of mCRPC often include pain in bones, fatigue, difficulty urinating, weight loss, and general weakness. As the cancer spreads, it can impair the function of other organs, depending on the site of metastasis. Diagnosis of mCRPC usually involves a combination of tests, including prostate-specific antigen (PSA) blood tests, imaging studies like CT scans, MRIs, or bone scans, and sometimes biopsies to confirm the spread and resistance to treatment. Treatment options for mCRPC are more complex and may include newer hormonal therapies (e.g., abiraterone, enzalutamide), chemotherapy (docetaxel or cabazitaxel), immunotherapy (e.g., sipuleucel-T), or targeted therapies such as PARP inhibitors. Bone-targeting therapies, radiation, and palliative care can also be used to manage symptoms and improve the quality of life. Treatment is typically tailored to the individual based on the extent of the disease and the patient health. Find out more about mCRPC treatment drugs @ Drugs for Metastatic Castration-Resistant Prostate Cancer Treatment A snapshot of the mCRPC Pipeline Drugs mentioned in the report: Learn more about the emerging mCRPC pipeline therapies @ Metastatic Castration-Resistant Prostate Cancer Clinical Trials Metastatic Castration-Resistant Prostate Cancer Therapeutics Assessment The mCRPC pipeline report proffers an integral view of the mCRPC emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Metastatic Castration-Resistant Prostate Cancer Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Oral, Intravenous, Subcutaneous Therapeutics Assessment By Molecule Type: Small molecule, Cell therapy, Peptides, Polymer, Small molecule, Gene therapy Therapeutics Assessment By Mechanism of Action: Androgen receptor degradation enhancers, Antibody-dependent cell cytotoxicity, Proto-oncogene protein c-akt inhibitors, Androgen receptor antagonists, Bromodomain and extraterminal domain protein inhibitors, Cyclin-dependent kinase 4 inhibitors, Cyclin-dependent kinase 6 inhibitors, Ionizing radiation emitters, PPAR alpha antagonists. Key Metastatic Castration-Resistant Prostate Cancer Companies: Regeneron Pharmaceuticals, AstraZeneca, Hinova Pharmaceuticals, Zenith Epigenetic, Eli Lilly and Company, Astellas Pharma, Seagen, Pfizer, Progenics Pharmaceutical, Molecular Insight Pharmaceuticals, Bayer, Accutar Biotechnology Inc, Hinova Pharmaceuticals, Forma Therapeutics, Inc., HALDA THERAPEUTICS INC., Tavanta Therapeutics, Lantheus, Pfizer, AB Science, Syntrix Pharmaceuticals, Exelixis, Laekna Therapeutics Shanghai Co. Ltd., Cardiff Oncology, Ipsen, Norroy Bioscience, Astellas Pharma, Novartis, Johnson & Johnson, Tempest Therapeutics, and others. Key Metastatic Castration-Resistant Prostate Cancer Pipeline Therapies: REGN 4336, Capivasertib, Deutenzalutamide, ZEN003694, Abemaciclib, Enfortumab vedotin, Talazoparib, I-131-1095, Pelgifatamab corixetan, AC176, HP518, FT-7051, HLD-0915, TAVT-45, PNT2002, Mevrometostat, Masitinib, SX-682, XL092, LAE001, Onvansertib, Tazemetostat, 177Lu-NYM032, PRL-02, 225 Actinium PSMA 617, ARX51, TPST-1120, and others. Dive deep into rich insights for new drugs for mCRPC treatment, visit @ Metastatic Castration-Resistant Prostate Cancer Drugs Table of Contents For further information on the mCRPC Cancer pipeline therapeutics, reach out @ Metastatic Castration-Resistant Prostate Cancer Treatment Drugs Related Reports Metastatic Castration-Resistant Prostate Cancer Market Metastatic Castration-Resistant Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCRPC companies including AstraZeneca, Merck Sharp & Dohme, Hinova Pharmaceuticals, Pfizer, Astellas Pharma, Modra Pharmaceuticals, AB Science, Eli Lilly and Company, Zr Pharma & GmbH, Bristol-Myers Squibb, Ipsen, Exelixis, Takeda, Janssen Research & Development, Tesaro, Lantheus Holdings, Kintor Pharmaceutical, MacroGenics, Daiichi Sankyo, Madison Vaccines, Novartis, Point Biopharma, Xencor, Essa Pharma, Telix International, Bayer, Arvinas, among others. Metastatic Prostate Cancer Market Metastatic Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key metastatic prostate cancer companies including AstraZeneca, Arvinas, Madison Vaccines, Phosplatin Therapeutics, Hinova Pharmaceuticals, Bristol Myers Squibb, Merck, MacroGenics, Daiichi Sankyo, Seagen, Taiho Pharmaceutical, Modra Pharmaceuticals, Xencor, Point Biopharma, Lantheus Holdings, Zenith Epigenetics, Essa Pharma, Telix Pharmaceuticals, Kintor Pharmaceutical, AB Science, Eli Lilly and Company, Exelixis among others. Metastatic Castration-Sensitive Prostate Cancer Market Metastatic Castration-Sensitive Prostate Cancer Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key mCSPC companies including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. Metastatic Castration-Sensitive Prostate Cancer Pipeline Metastatic Castration-Sensitive Prostate Cancer Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, including clinical and non-clinical stage products, and the key mCSPC companies, including Myovant Sciences, Pfizer, Bayer, Orion, Novartis, AstraZeneca, Pfizer, Janssen, Merck, Eli Lilly, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

快速通道免疫疗法临床1期临床结果

2023-12-16

·药智网

前列腺癌药物的江湖纷争

前列腺癌的病因及发病机制十分复杂，其确切病因尚不明确。目前，前列腺癌早期可以通过手术、放疗、雄激素剥夺疗法(ADT)等进行成功治疗。但前列腺癌早期临床症状不明显，因此确诊时多数患者已属中晚期。近年来，随着一系列突破性进展的取得，前列腺癌药物的江湖纷争出现新的变化。注：本文仅作信息交流之目的，文中观点不代表药智网立场，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。01治疗方案有限，常见疗法包括化疗和内分泌疗法前列腺是雄激素依赖性器官，其生长发育与雄激素受体（AR）信号通路密切相关。AR在前列腺癌的发生、发展中起重要作用。AR通路抑制剂通过减少循环睾酮及雄激素-AR受体复合物，降低前列腺癌中的AR活性。目前，前列腺癌早期可以通过手术、放疗、雄激素剥夺疗法(ADT)等进行成功治疗。但前列腺癌早期临床症状不明显，因此确诊时多数患者已属中晚期，中晚期前列腺癌患者首选治疗方案为雄激素剥夺治疗(ADT)。ADT是晚期转移性前列腺癌患者的主要全身性基础治疗，也是各种新型联合治疗方案的基础。ADT包括多种实施方案，其中，单纯去势（外科或者药物去势）是最广为接受的核心治疗方式。近年来，出现了一系列突破性进展，主要是ADT与新型内分泌治疗药物或化疗药物的联合使用，改善了转移性前列腺癌的总体治疗效果。但最终，几乎所有患者经ADT治疗18~36个月后会出现药物抵抗，最终进展为去势抵抗性前列腺癌(CRPC)，此阶段的患者中位生存期大约只有12个月。下图为前列腺癌进展到不同阶段的治疗方法及用药方案。注：本文仅作信息交流之目的，文中观点不代表药智网立场，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。表1 前列腺癌主要治疗药物分类及作用机制数据来源：公开数据，药智咨询整理02第二代AR拮抗剂等新药的上市，刺激前列腺癌市场增长2021年，中国前列腺癌治疗药物市场规模为77.45亿元，2017-2021年复合增长率为14.79%。同时，近年来多个第二代AR拮抗剂在国内上市，包括恩扎卢胺（2019年），阿帕他胺（2020年），瑞维鲁胺（2022年6月）等，预计第二代AR拮抗剂等新药的上市将促进前列腺癌治疗药物市场持续增长。图1 中国前列腺癌治疗药物市场规模数据来源：药智数据，药智咨询整理2021年，中国前列腺癌治疗药物中市场份额最高的为亮丙瑞林（27.16%），其次为戈舍瑞林（23.61%）。这两个药物为GnRHR激动剂，是雄激素剥夺疗法（ADT）中常用的药物，ADT是激素敏感性前列腺癌联合用药的基础，所以市场份额高。阿比特龙是由强生公司开发的CYP17A酶不可逆抑制剂，CYP17A酶是雄激素生物合成过程中的限速酶，存在于睾丸、肾上腺以及前列腺癌细胞中。2011年获FDA批准上市，2015年被美国泌尿外科协会推荐用于治疗各种类型的转移性去势抵抗性前列腺癌（mCRPC）患者，2015年4月在中国获批上市。阿比特龙临床试验疗效显著，2017年进入医保，进入医保后迅速放量，2017-2021年复合增长率高达71.34%。2021年，阿比特龙销售额达13.92亿元，同比2020年增长5.19%。阿比特龙2020年进入国家集采，进入集采后阿比特龙的销售额依然保持增长。恩扎卢胺由Medivation和安斯泰来公司合作开发，2012年获FDA批准用于治疗CRPC，2019年在中国获批上市。恩扎卢胺是第二代非甾体类抗雄激素药物，相比于第一代AR抑制剂仅竞争性地结合AR，其抗AR活性比第一代强数倍。恩扎卢胺是少数无需联合类固醇激素治疗的选择，相较于阿比特龙（需要与泼尼松联用以控制不良反应）具有显著安全性优势。2019年至今在全球抗前列腺癌市场中恩扎卢胺所占市场份额最大；而国内该药于2019年上市，上市后销售额增长迅速，2021市场规模为1.96亿元，同比2020年增长4170.32%，预计未来国内用药结构将向全球看齐，恩扎卢胺将保持高速增长。03在研药物数量多，靶点集中在FOLH1、AR等全球前列腺癌在研治疗药物约657个，中国前列腺癌在研治疗药物约145个；全球在研靶点集中在PSMA（FOLH1）、AR、GnRH receptor等靶点。图2 全球及中国前列腺癌治疗上市在研药物数量和靶点图片来源：药智数据-全球药物分析系统前列腺特异性膜抗原（PSMA,又称叶酸水解酶1（FOLH1））是一种跨膜糖蛋白，目前的研究表明PSMA在超过90%的前列腺癌细胞表面都出现了过表达，并且在晚期和去势抵抗性患者的癌细胞中表达水平更高。可通过影像学评估PSMA的表达情况，与传统的扫描检查相比，PSMA PET/CT在检测前列腺癌病灶方面有着独特的优势，在前列腺癌早期和病程分期上能做出更有效的判断，PSMA PET/CT凭借其高特异性多模态显像的优势显著提高诊断敏感性和准确性。目前上市和在研的PSMA药物多是放射性药物，包括已上市药物177Lu-PSMA-617，和在研药物PNT2002（177Lu标记的放射性药物）、131I-MIP-1095（131I标记的放射性药物）、225Ac-PSMA-I&T（225Ac标记的放射性药物）等。其中，诺华研发的放射性配体疗法（177Lu-PSMA-617）于2022年3月获FDA批准，治疗范围包括已扩散的、接受过其他治疗的前列腺癌患者。177Lu-PSMA-617包括靶向性化合物（PSMA-617）和治疗性同位素（177Lu），能够实现精准癌症治疗。177Lu-PSMA-617与表达PSMA的前列腺癌细胞结合，反射性元素产生的放射线更集中在肿瘤组织局部，在杀死癌细胞的同时减少对健康细胞的损伤。目前，mCRPC一线治疗主要推荐优选新型内分泌治疗（NHT），国内可及的方案有恩扎卢胺、阿比特龙等。但临床结果发现新型内分泌治疗药物并不是对所有的去势抵抗性前列腺癌（CRPC）都有效，一部分患者对这些药物存在原发性耐药，对于初始有效的mCRPC患者，最终也还是发生继发性耐药。耐药机制主要是由于AR基因发生变异，包括AR扩增、AR突变、AR剪切变异体（ARVs）等。沉默AR基因表达的治疗策略是治疗CRPC的潜在有效方法。反义寡核苷酸（ASO）可以从本质上阻断特定基因靶标，阻止其相关蛋白质的合成，因此已成为多种人类疾病的替代治疗方法。阿斯利康开发了反义核苷酸AZD5321，临床前研究表明，AZD5312与AR mRNA杂交，从而阻断AR蛋白的翻译，能够有效抑制全长AR(AR-FL)及其剪接变体的表达，这既能抑制AR诱导的肿瘤细胞生长，又能促进AR过表达的肿瘤细胞凋亡，从而在恩杂鲁胺耐药的CRPC模型中产生抗肿瘤活性。但该药物于2014年开始进行I期临床试验，目前暂无进展。04小结目前针对晚期前列腺癌治疗通路有限，深受现有治疗方案交叉耐药的瓶颈；mCRPC的中位生存时长短，患者往往进展到二线治疗时丧失治疗积极性，存在巨大未被满足的临床需求。亟需一个全新的治疗方式和理念，带领临床患者走出治疗困境。注：本文仅作信息交流之目的，文中观点不代表药智网立场，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。参考文献：[1]闵淑慧，胡依，郭芮绮.1990-2019年中国前列腺癌疾病负担分析及趋势预测.中国肿瘤ISSN 1004-0242，CN 11-2859/R.[2]http://www.phirda.com/artilce_27200.html?cId=1[3]De Velasco MA,Kura Y,Sakai K,Hatanaka Y,Davies BR,Campbell H,Klein S,Kim Y,MacLeod AR,Sugimoto K,Yoshikawa K,Nishio K,Uemura H.Targeting castration-resistant prostate cancer with androgen receptor antisense oligonucleotide therapy.JCI Insight.2019 Sep 5;4(17):e122688.声明：本内容为作者独立观点，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 | 八斤转载开白 | 马老师 18996384680（同微信）如需定制医药咨询服务，请扫描下方二维码咨询！阅读原文，是受欢迎的文章哦

放射疗法抗体药物偶联物

100 项与 131I-MIP-1095 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB14978

研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
转移性去势抵抗性前列腺癌	临床2期	美国	Progenics Pharmaceuticals, Inc.	2019-05-30
转移性去势抵抗性前列腺癌	临床2期	加拿大	Progenics Pharmaceuticals, Inc.	2019-05-30
前列腺癌	临床1期	美国	Molecular Insight Pharmaceuticals, Inc.	2008-05-01

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临床结果

适应症

分期

评价

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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


NCT03939689 (ARROW, CTgov)	临床2期	转移性去势抵抗性前列腺癌	120	Enzalutamide (Enzalutamide)	鑰鹹齋鬱窪窪範鏇鬱鑰 = 壓醖壓衊鹹窪艱衊壓繭膚網選繭壓淵選淵遞遞 (簾觸範窪窪廠顧願衊遞, 製淵選遞鹽製網壓構艱 ~ 願鑰襯蓋鑰齋襯醖鹽夢) 更多	-	2025-10-14
				Enzalutamide+I-131-1095 (I-131-1095 in Combination With Enzalutamide)	鑰鹹齋鬱窪窪範鏇鬱鑰 = 襯選遞觸觸廠網齋觸鏇膚網選繭壓淵選淵遞遞 (簾觸範窪窪廠顧願衊遞, 選淵顧蓋糧顧夢繭窪糧 ~ 築遞糧鹽鹹餘憲網繭襯) 更多
NCT03939689 (ARROW, ESMO2024) 人工标引	临床2期	转移性去势抵抗性前列腺癌	120	Enzalutamide+131I-LNTH-1095	顧選餘鏇鏇廠觸憲窪餘(淵鹹鹽製築襯簾繭壓廠) = 窪襯簾醖憲網範築夢膚艱積夢淵簾餘膚艱鑰選 (繭餘憲構膚願鬱膚醖廠 ) 更多	积极	2024-09-15
				Enzalutamide	顧選餘鏇鏇廠觸憲窪餘(淵鹹鹽製築襯簾繭壓廠) = 糧衊襯襯積網鹹鹹襯齋艱積夢淵簾餘膚艱鑰選 (繭餘憲構膚願鬱膚醖廠 ) 更多
NCT03030885 (Phase 1, Pubmed \| Clin Nucl Med)	临床1期	转移性去势抵抗性前列腺癌 prostate-specific antigen	9	131I-MIP-1095 75 mCi	壓遞廠顧築糧廠艱衊鹹(獵襯壓鏇鏇鬱餘糧願艱) = Grade 1-2 thrombocytopenia most commonly occurred 築製壓廠顧鏇範觸衊齋 (構製衊構遞簾製選簾鏇 ) 更多	积极	2023-11-01
EANM2009	临床1期	转移性前列腺癌 prostate specific membrane antigen (PSMA)	7	123 I-MIP-1072 (123 I-MIP-1072)	繭膚願簾鬱網壓範壓艱(築醖廠夢醖壓鹹齋鑰蓋) = 願遞鬱廠衊壓衊範鏇壓築齋淵網構遞蓋選鏇積 (窪艱憲窪簾窪襯範糧壓 ) 更多	积极	2009-08-08
				123 I-MIP-1095	繭膚願簾鬱網壓範壓艱(築醖廠夢醖壓鹹齋鑰蓋) = 鹹積觸遞繭築蓋築壓窪築齋淵網構遞蓋選鏇積 (窪艱憲窪簾窪襯範糧壓 ) 更多