Researchers want to learn if MK-5684 (the study medicine) can treat breast cancer, ovarian cancer, and endometrial cancer. MK-5684, the study medicine, is designed to treat cancer by blocking the body from making steroid hormones.
Researchers will compare MK-5684 to the standard treatments for each cancer type in this study.
The goal of this study is to learn if people who receive MK-5684 live longer without the cancer growing or spreading compared to people who receive a standard treatment.

开始日期2025-08-11

申办/合作机构

Merck Sharp & Dohme LLC

NCT06863272

/ Recruiting临床1/2期

MK-2400-01A Substudy: A Phase 1/2, Open-label Umbrella Substudy of MK-2400-U01 Master Protocol to Evaluate the Safety and Efficacy of Ifinatamab Deruxtecan-based Treatment Combinations or Ifinatamab Deruxtecan Alone in Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) (IDeate-Prostate02)

The purpose of this substudy is to assess the efficacy and safety of ifinatamab deruxtecan (I-DXd), given alone or with other treatments in participants with metastatic castration-resistant prostate cancer (mCRPC). The goals of this study are to learn about:
* The safety of the study treatment and if people tolerate it.
* A safe dose level of I-DXd that can be used with other treatments.
* Participant levels of prostate specific antigen (PSA) during treatment.

开始日期2025-07-03

申办/合作机构

Merck Sharp & Dohme LLC

[+1]

NCT06860243

/ Active, not recruiting临床1期

An Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of MK-5684 in Male Participants With Moderate Hepatic Impairment

Researchers have designed a study medicine called opevesostat as a new way to treat prostate cancer.
The purpose of this study is to learn what happens to opevesostat in a person's body over time (a pharmacokinetic [PK] study). Researchers will compare what happens to opevesostat in the body when it is given to healthy participants and participants with moderate hepatic (liver) impairment.

开始日期2025-05-13

申办/合作机构

Merck Sharp & Dohme LLC

100 项与 Opevesostat 相关的临床结果

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100 项与 Opevesostat 相关的转化医学

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100 项与 Opevesostat 相关的专利（医药）

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项与 Opevesostat 相关的文献（医药）

2024-05-01·Current opinion in oncology

Targeting androgen biosynthesis in prostate cancer: implications on endocrine physiology

Review

作者: Malek, Rana ; Hussain, Arif ; Kango, Ghazal ; Mannuel, Heather

Purpose of review:

Targeting specific steroidogenic enzymes is effective in decreasing testosterone synthesis, resulting in significant antitumor effects in prostate cancer. Such treatments result in disruptions of complicated and intertwining pathways with systemic physiologic consequences via effects on the adrenal gland and renin–angiotensin–aldosterone axis. This review highlights some of these aspects that need to be taken into consideration when treating patients with androgen biosynthesis inhibitors.

Recent findings:

Targeting CYP17A1, a key enzyme involved in androgen biosynthesis, is a well established treatment in prostate cancer. More recently, efforts are underway to target a gatekeeper enzyme of steroidogenesis, CYP11A1. This enzyme mediates conversion of cholesterol to pregnenolone, the first step in steroid hormone biogenesis. Studies are beginning to demonstrate antitumor effects of ODM-208, a CYP11A1 inhibitor in prostate cancer. Although anticipated to have a therapeutic role in prostate cancer, there are potential downstream effects of CYP11A1 targeting arising from suppression of the entire adrenal cortex, including long-term adrenal insufficiency and possibly cardiovascular dysregulation.

Summary:

Agents targeting androgen biosynthesis can have systemic implications. Balancing management of prostate cancer with better understanding of the mechanisms associated with potential side effects will allow for patients to obtain improved antitumor benefit while mitigating against treatment-associated adverse effects.

2024-01-23·NEJM evidence

Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer

Article

In the Original Article, "Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer", originally published December 26, 2023 (DOI: https://doi.org/10.1056/EVIDoa2300171), in the Abstract, under "Background", the sentence "ODM-208, a novel inhibitor of cytochrome P450 17A1 …" should have read "ODM-208, a novel inhibitor of cytochrome P450 11A1…" A corrected version of the article has been posted at evidence.nejm.org.

2023-12-26·NEJM evidence

Targeted Inhibition of CYP11A1 in Castration-Resistant Prostate Cancer

Article

作者: Ikonen, Tarja ; Fléchon, Aude ; Cook, Natalie ; Barthélémy, Philippe ; van der Voet, Johannes ; Roubaud, Guilhem ; Antonarakis, Emmanuel S. ; Pohjanjousi, Pasi ; Garratt, Chris ; Utriainen, Tapio ; Baldini, Capucine ; Peters, Niamh ; Ratta, Raffaele ; Parikh, Omi ; Tanner, Minna ; Bernard-Tessier, Alice ; Fizazi, Karim ; Gravis, Gwenaëlle ; Jones, Robert ; Joensuu, Heikki

BACKGROUND: Prostate cancer is regulated by steroid hormones, even in castration-resistant disease. ODM-208, a novel inhibitor of cytochrome P450 11A1 (which catalyzes the first step of steroid-hormone biosynthesis), was investigated in patients with heavily pretreated metastatic castration-resistant prostate cancer (mCRPC). METHODS: CYPIDES is a first-in-human phase 1 (3 + 3 design) and phase 2 study. We administered ODM-208 twice daily with glucocorticoid/mineralocorticoid replacement and ongoing androgen deprivation therapy to adults with previously treated mCRPC, regardless of androgen receptor gene (AR) ligand-binding domain mutations (phase 1) and with activating AR ligand-binding domain mutations (ARmut; phase 2). Safety, pharmacokinetics, steroid-hormone pharmacodynamics, and preliminary efficacy were the key outcomes. RESULTS: Ninety-two patients received one or more doses of ODM-208: 47 in phase 1 (20 [42.6%] with ARmut) and 45 in phase 2 (all ARmut). A dose of ODM-208 of 5 mg twice a day with dexamethasone 1 mg/fludrocortisone 0.1 mg provided a balance between decreased steroidogenesis and toxicity. Treatment-related adrenal insufficiency was the most common toxicity in phase 1 (n=17, 36.2%; necessitating ODM-208 discontinuation in one patient); this toxicity occurred in six patients (13.3%) at 5 mg twice a day in phase 2. Median circulating testosterone levels declined from 3.0 ng/dl (interquartile range, 1.3 to 6.2 ng/dl) at baseline to undetectable levels within the first week of ODM-208 5 mg twice a day treatment in 46 of 53 (87%) patients. A decrease in prostate-specific antigen levels of 50% or more occurred in 14 of 19 (73.7%) patients with ARmut and 2 of 23 (8.7%) patients with AR wild type in phase 1 and in 24 of 45 (53.3%) patients with ARmut in phase 2. CONCLUSIONS: ODM-208 potently inhibited steroid-hormone biosynthesis with the expected toxicity of adrenal insufficiency. Evidence of antitumor activity was observed in this heavily pretreated mCRPC population, especially in those with ARmut. (Funded by Orion Pharma; ClinicalTrials.gov number, NCT03436485.)

项与 Opevesostat 相关的新闻（医药）

2025-11-12

·晴医家园

一文看全！2025前列腺癌新药汇总，覆盖核药、靶向抑制剂、ADC、PROTAC

对晚期前列腺癌患者而言，治疗的最大问题在于，随着治疗时间延长，病情通常会出现去势抵抗，变成转移性去势抵抗性前列腺癌（mCRPC），这是前列腺癌最难治疗的阶段，预后不太好，而且治疗选择有限，成为目前前列腺癌新药研发最关注的领域。当下前列腺癌的新药研发主要集中在四个方向，且近年来这些领域也取得了显著进展，为患者提供了更多有价值的治疗选择。 ● 核药：前列腺癌当前最热门的研发领域。PSMA在约80%前列腺癌中高表达，是前列腺癌核素领域的关键靶点，通过精准靶向PSMA实现对肿瘤细胞的杀伤，延长患者生存期和生活质量。 ● 靶向治疗：以AR抑制剂、PARP抑制剂、EZH2抑制剂、CYP11A1抑制剂为主要的前列腺癌靶向抑制剂方向，在前列腺癌研发中占据重要地位。 ● ADC：ADC（抗体药物偶联物）是近年来的新兴方向，Trop-2、PSMA、B7-H3、HER3等靶点，是前列腺癌ADC的重点探索方向。 ● 其他治疗：PROTAC、细胞疗法等创新前沿疗法，也在前列腺癌领域开展研究，为耐药或难治性患者提供了新的希望。我们平台给患者及家属整理更新了[前列腺癌]新药汇总，相关临床试验项目汇总表如下，后续有相关新项目会陆续更新中，具体项目信息添加医学老师咨询。前列腺癌临床试验👇 药物类型用药方案分期 CYP11A1抑制剂 MK-5684片 III期靶向EZH2抑制剂 PF-06821497 III 期靶向EZH2抑制剂 XNW5004 Ib/II期 TF靶向ADC XNW28012 I/II期 B7-H3靶向ADC QLC5508(MHB088C) I/II期 177Lu-PSMA 镥[177Lu]-vipivotide tetraxetan(617)Pluvicto II期 177Lu-PSMA 镥[177Lu]-XT033 I/II 期 177Lu-PSMA 镥[177Lu]-NYM032 I/II 期 177Lu-PSMA 镥[177Lu]-JH020002 I/II期 225AC-PSMA [225AC]AC-PSMA-XT III期 AR PROTAC降解剂 QLH12016 Ib/II期前沿新药/技术临床试验正在进行中 ● 精准靶向药：EGFR、KRAS、HER2、cMET、BRAF、FGFR、ALK、ROS1、RET、NTRK等常见与罕见基因突变 ● 细胞治疗：CAR-T、TCR-T、TIL细胞回输等 ● 新型药物：ADC药物、肿瘤疫苗、溶瘤病毒等 ● 精准放射/介入：硼中子俘获治疗、镥177、钇90、纳米刀等肿瘤类型正在招募中肺癌（肺腺癌、肺鳞癌、小细胞肺癌）、乳腺癌、消化道肿瘤（食管癌、胃癌、肝癌、胆管细胞癌、胰腺癌、结直肠癌）、妇科肿瘤（宫颈癌、卵巢癌、子宫内膜癌）、泌尿系统肿瘤（前列腺癌、尿路上皮癌、肾癌）、头颈鳞癌、鼻咽癌、神经内分泌癌（肺外）、黑色素瘤、肉瘤、恶性血液疾病、淋巴瘤等。如何申请临床试验？想申请参加临床试验的患者，可通过联系晴医家园平台医学老师（微信号：chenlan160）了解详情或进行申请。（专业可靠的申请渠道）近些年，肿瘤新药不断涌现，临床试验已经是很多晚期肿瘤患者重点考虑的一环了。目前治疗阶段是否应该参加新药试验，要参加哪个新药试验，很多患者并不太清晰，希望我们能用专业的新药招募经验来帮助到患者及家属，提供更合理最大可能获益的治疗选择。点击名片，关注更多肿瘤新药 👇

抗体药物偶联物蛋白降解靶向嵌合体免疫疗法细胞疗法疫苗

2025-10-26

·浊水桥

靶向前列腺癌中的雄激素受体改变 | ESMO25

摘要 2025年ESMO年会展示了针对前列腺癌雄激素受体（AR）改变的新型靶向治疗进展，重点包括AR扩增、剪接变异和突变的临床影响，以及AR降解剂和CYP11A1抑制剂的新疗法潜力，部分药物在耐药患者中展现显著疗效。概述在2025年ESMO年会上，Alice Bernard-Tessier博士介绍了针对前列腺癌雄激素受体（AR）改变的最新靶向治疗策略。亮点 🎯 AR改变主导耐药：第二代AR抑制剂治疗后，耐药仍主要由AR改变驱动，这是晚期前列腺癌最常见的基因改变。 📊 AR扩增最常见：在转移性去势抵抗性前列腺癌（mCRPC）中，AR扩增约占所有改变的40-60%。 🔀 剪接变异占重要比例：AR剪接变异是第二常见的改变类型，约占15-55%。 🧬 AR突变预后较差：AR突变约占15-25%，通常发生在配体结合域，与预后较差相关。 💊 新机制药物研发：雄激素受体降解剂（如BMS-986365、ARV-766）和CYP11A1抑制剂（如Opevesostat）展现出潜力。 🧪 临床试验结果喜忧参半：galeterone、cirtuvivint等早期药物疗效有限，但新型降解剂在AR配体结合域突变患者中PSA50应答率达43-53%。 ⚠️ 安全性需重点关注：新疗法需关注QT间期延长、疲劳、腹泻和肾上腺功能不全等副作用。配图 mCRPC肿瘤中AR改变富集情况示意图，显示AR改变在晚期前列腺癌中的主导地位。 AR扩增机制示意图，展示约40-60%的AR改变涉及上游增强子或拷贝数增益。 AR剪接变异类型分布，包括替代剪接和基因结构重排，占总改变的15-55%。 AR突变分布图谱，突变主要发生在配体结合域，占总改变的15-25%。 ARMOR3-SV III期试验设计，比较galeterone与恩杂鲁胺在AR-V7阳性患者中的效果。 cirtuvivint联合阿比特龙治疗的疗效数据，显示适度的PSA反应。 gumelutamide在I期剂量递增队列中的疗效结果。 BMS-986365的双重作用机制示意图，展示其作为AR降解剂和拮抗剂的创新设计。 CC-94676-PCA-001试验患者基线特征，包括既往治疗史和剂量分组。 BMS-986365在野生型和突变型AR患者中的临床获益对比。 ARV-766的作用特点，突出其对多种AR突变体（L702H、H875Y、T878A）的靶向能力。 ARV-766在AR配体结合域突变患者中的疗效数据。 Bernard-Tessier博士团队的研究发现，从泼尼松换用地塞米松可改善无进展生存期。 Opevesostat是一种非类固醇选择性CYP11A1抑制剂，最近在II期CYPIDES试验中进行了评估 Opevesostat在AR配体结合激活突变患者中的PSA50应答率达53%。新疗法的安全性关注点汇总，包括心电、消化和内分泌系统副作用。相关问题1. 雄激素受体降解剂与传统AR抑制剂的根本区别是什么？作用机制差异：传统AR抑制剂：如恩杂鲁胺主要通过竞争性结合AR的配体结合域来阻断雄激素信号传导，但无法消除已有的AR蛋白。 AR降解剂：采用PROTAC技术，通过泛素-蛋白酶体系统直接降解AR蛋白，从源头上清除靶点。覆盖范围优势：传统抑制剂：主要针对野生型AR，对某些突变体效果有限。 AR降解剂：能同时靶向野生型和多种突变AR（包括L702H、H875Y、T878A），克服了由特定突变引起的耐药。临床效果对比：在CC-94676-PCA-001试验中，BMS-986365在既往接受过多种治疗的重度预处理mCRPC患者中显示出持续疗效，且在AR配体结合域突变患者中效果更显著。耐药性管理：传统抑制剂可能因F877L等突变而产生"拮抗剂转激动剂"效应，而降解剂因其作用机制不受此影响。2. 目前针对雄激素受体剪接变异有哪些具体治疗策略？直接靶向途径： Galeterone：作为CYP17抑制剂，在ARMOR3-SV III期试验中针对AR-V7阳性患者进行评估。但该研究因不太可能达到改善无进展生存期的主要终点而提前终止。联合治疗探索： Cirtuvivint：pan CLK/DYRK抑制剂，与阿比特龙联合使用时显示出适度的PSA30和PSA50反应，3/3患者达到疾病稳定。新型拮抗剂开发： Gumelutamide (TAS3681)：第三代AR拮抗剂，但在I期剂量递增队列中活性有限。 N端域靶向策略： Masofaniten (EPI-7386)：专门靶向AR N端域的小分子药物。在ONCT-534随机II期研究中与恩杂鲁胺联合使用，但因联合组PSA90率（64%）低于单用恩杂鲁胺组（74%）而提前终止。技术挑战：开发针对剪接变异的有效疗法面临较大困难，因为剪接变异体缺乏配体结合域，传统激素靶向药物对其无效。3. 如何理解CYP11A1抑制剂在前列腺癌治疗中的独特价值？作用机制深度解析：源头阻断：CYP11A1是类固醇合成的限速酶，催化胆固醇转化为孕烯醇酮。抑制该酶能从最上游阻断所有下游类固醇激素（包括雄激素、雌激素、孕激素等）的合成。克服突变耐药：对于因AR突变（如L702H对皮质类固醇、T878A对孕酮、H875Y对雌二醇异常激活）导致的耐药，CYP11A1抑制剂能减少这些异常激活配体的产生。临床验证数据： CYPIDES II期试验：评估opevesostat在mCRPC患者中的疗效，这些患者在接受≥1种新型激素药物和≥1种紫杉烷后疾病进展。疗效表现：在AR配体结合激活突变患者中，PSA50应答率达53%，且37.8%的患者治疗超过6个月。治疗管理要求：肾上腺支持治疗：由于强烈抑制肾上腺类固醇合成，需要同时给予地塞米松（1-1.5mg）和氟氢可的松（0.1mg）以防止肾上腺功能不全。优势定位：与其他AR靶向药物相比，CYP11A1抑制剂提供了一种"全阻断"策略，特别适用于存在多种AR突变或对现有AR靶向药物产生广泛耐药的患者。

临床结果临床2期

2025-06-05

·PipelineReview

Acerand Therapeutics Initiates First-in-Human Phase I Clinical Trial of ACE-232, a Novel CYP11A1 Inhibitor for Advanced Prostate Cancer

SHANGHAI, China & INDIANAPOLIS, IN, USA I June 04, 2025 I Acerand Therapeutics, a clinical-stage biotech company focusing on the discovery and development of innovative small-molecule therapies in oncology, today announced the dosing of the first patient in its first-in-human Phase I clinical trial (NCT06801236) of ACE-232, a novel oral inhibitor of CYP11A1. The trial is being conducted in patients with metastatic castration-resistant prostate cancer (mCRPC). This multicenter Phase I study is being conducted in both the United States and China. The study comprises two parts: a dose-escalation phase (Phase IA) and a dose-optimization phase (Phase IB). The primary objectives are to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), as well as preliminary clinical activity of ACE-232, and to determine the recommended Phase II dose (RP2D). Professor Emmanuel Antonarakis, Director of Genitourinary Oncology at Masonic Cancer Center, University of Minnesota, is serving as the global coordinating Principal Investigator for the study. “I would like to congratulate the Acerand team, the research staff, and the first patient for helping us to reach this important milestone,” says Dr. Antonarakis. Preclinical data demonstrated that ACE-232 possesses superior potency, efficacy, and pharmacokinetic properties (flat PK curve and long half-life profile) compared to other investigational CYP11A1 inhibitors, including MK-5684 (Opevesostat, formerly known as ODM-208). ACE-232 showed excellent tolerability in preclinical models, presenting a wide therapeutic window for clinical development. The initiation of this trial marks a significant milestone for Acerand, representing its first clinical study in the United States and highlighting its strategic commitment to the global development of innovative cancer therapies that address major unmet medical needs. About ACE-232 ACE-232 is a highly potent and selective small-molecule inhibitor of CYP11A1, a key adrenal enzyme involved in the first and rate-limiting step of steroid hormone biosynthesis. By targeting CYP11A1, ACE-232 aims to suppress the production of androgens and other steroid hormones, offering a novel therapeutic mechanism for the treatment of androgen-dependent (including enzalutamide or abiraterone-resistant) prostate cancer. About Acerand Therapeutics Acerand Therapeutics is a biotech company dedicated to discovering and developing novel small-molecule therapies for oncology and metabolic diseases. With research and development hubs in Shanghai, China, and Indianapolis, USA, ACE-232 leverages its proprietary innovation platform and operational efficiency to deliver a highly differentiated pipeline of drug candidates from discovery to clinical trials. http://acerand.com/ SOURCE: Acerand Therapeutics

临床1期

100 项与 Opevesostat 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性前列腺癌	临床3期	美国	Merck Sharp & Dohme LLC	2023-12-31
转移性前列腺癌	临床3期	巴西	Merck Sharp & Dohme LLC	2023-12-31
转移性前列腺癌	临床3期	智利	Merck Sharp & Dohme LLC	2023-12-31
转移性前列腺癌	临床3期	中国台湾	Merck Sharp & Dohme LLC	2023-12-31
转移性前列腺癌	临床3期	泰国	Merck Sharp & Dohme LLC	2023-12-31
转移性前列腺癌	临床3期	英国	Merck Sharp & Dohme LLC	2023-12-31
去势抵抗性前列腺癌	临床3期	马来西亚	Merck Sharp & Dohme LLC	2023-12-18
去势抵抗性前列腺癌	临床3期	秘鲁	Merck Sharp & Dohme LLC	2023-12-18
去势抵抗性前列腺癌	临床3期	西班牙	Merck Sharp & Dohme LLC	2023-12-18
去势抵抗性前列腺癌	临床3期	土耳其	Merck Sharp & Dohme LLC	2023-12-18

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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


NCT03436485 (CYPIDES, ESMO2024) 人工标引	临床2期	转移性去势抵抗性前列腺癌二线 AR-LBD mutations	134	Opevesostat 5mg BID	願鑰憲衊憲夢鑰膚網鹽(襯簾醖衊廠繭夢齋膚壓) = 廠夢構築鬱衊齋製餘鹽餘網夢餘製壓構淵鹽遞 (鑰膚襯膚築獵夢顧願獵 ) 更多	积极	2024-09-15
				Opevesostat	願鑰憲衊憲夢鑰膚網鹽(襯簾醖衊廠繭夢齋膚壓) = 願壓積艱網餘膚觸餘淵餘網夢餘製壓構淵鹽遞 (鑰膚襯膚築獵夢顧願獵 ) 更多
NCT03436485 (CYPIDES, ASCO_GU2024) 人工标引	临床2期	转移性去势抵抗性前列腺癌 AR-LBD mutations	134	MK-5684 5mg BID (AR-LBD mutation-positive)	鹽膚襯憲選襯艱膚觸製(糧製憲築衊憲製鹽鏇顧) = 鑰觸憲網築壓積繭鑰衊鬱簾範夢壓艱願遞鹹顧 (糧構餘網淵顧齋廠廠鬱 ) 更多	积极	2024-01-25
				MK-5684 5mg BID (AR-LBD mutation-negative)	壓齋構醖鏇壓鬱網膚鑰(範鏇積選鹹鬱構製選構) = 廠範繭鹽膚襯獵簾鏇鹹繭夢顧淵壓獵鏇淵鑰鏇 (獵窪夢築構膚夢醖醖遞 ) 更多
NCT03436485 (CYPIDES , Pubmed) 人工标引	临床1/2期	去势抵抗性前列腺癌 AR Mutation	92	ODM-208+glucocorticoid/mineralocorticoid replacement+androgen deprivation therapy (ARmut in phase 1)	鹹鏇獵襯齋醖衊簾窪淵(糧獵簾築鏇糧襯壓鬱淵) = Treatment-related adrenal insufficiency was the most common toxicity in phase 1 (n=17, 36.2%; necessitating ODM-208 discontinuation in one patient); this toxicity occurred in six patients (13.3%) at 5 mg twice a day in phase 2. 壓簾簾鏇鬱構構膚壓蓋 (糧範製夢憲蓋醖鹹繭鬱 )	积极	2023-12-26
				ODM-208+glucocorticoid/mineralocorticoid replacement+androgen deprivation therapy (AR wild type in phase 1)
NCT03436485 (CYPIDES, ESMO2022) 人工标引	临床2期	转移性去势抵抗性前列腺癌 AR LBD mutation	45	ODM-208+dexamethasone+fludrocortisone	製糧衊糧蓋鏇選範鏇簾(願壓餘顧糧網鹽廠襯糧) = 膚顧範憲淵鹹糧鹽製簾築獵製壓衊鬱鏇顧構積 (繭廠鹽鬱鏇蓋積窪壓繭 ) 更多	积极	2022-09-11
NCT03436485 (CYPIDES, Corporate Publications) 人工标引	临床1/2期	转移性去势抵抗性前列腺癌 AR LBD mutation	44	ODM-208	衊鏇鹽構蓋醖願蓋構顧(壓衊簾蓋襯鏇願遞艱遞) = severe adrenal insufficiency 32% 觸齋糧窪積鏇鹹遞醖遞 (範醖襯製積鏇範膚繭獵 )	积极	2022-02-18