A PHASE 1, OPEN-LABEL, FIXED SEQUENCE, 2-PERIOD, SINGLE-DOSE, CROSS-OVER STUDY TO ESTIMATE THE ABSOLUTE BIOAVAILABILITY OF VEPDEGESTRANT (ARV-471, PF-07850327) FOLLOWING ORAL AND INTRAVENOUS DOSING OF THE DRUG TO HEALTHY PARTICIPANTS

The purpose of this study is to learn how much of the study medicine called Vepdegestrant will reach the bloodstream when given orally compared to given intravenously.
This study is seeking participants who:
* are healthy males and healthy females who cannot have children.
* are 18 years or older.
* are healthy as decided by medical tests.
* have a body mass index (BMI) of 16 to 32 kilogram per meter squared.
* have a total body weight of more than 45 kilograms (99 pounds).
In Period 1, all participants will receive one dose of Vepdegestrant by IV. In Period 2, all participants will receive one dose of Vepdegestrant by mouth following a high-fat breakfast. The levels of Vepdegestrant in Period 1 will be compared to the levels of Vepdegestrant in Period 2 and the bioavailablility of the oral formulation of Vepdegestrant will be determined.
The study duration is 22 days and includes two periods. Participants will stay in the clinical research unit for 9 days (8 nights) during each period. A follow-up visit for each participant takes place at 28 to 35 days after taking the study medicine for the last time.

开始日期2025-04-03

申办/合作机构

Pfizer Inc.

[+1]

CTR20242782

/ Active, not recruiting临床2期

一项在 18 岁及以上 ER+/HER2- 晚期或转移性乳腺癌研究参与者中评估口服蛋白水解靶向嵌合体 Vepdegestrant（ARV-471/PF-07850327）联合 PF-07220060 治疗的耐受性、PK 和抗肿瘤活性的开放标签、干预性的安全有效性 Ib/II 期研究

II期主要目的：1. 评估 Vepdegestrant 联合 PF-07220060 治疗的临床抗肿瘤活性。II期次要目的：1. 确定 Vepdegestrant 联合 PF-07220060 治疗的其他抗肿瘤活性结局。2. 进一步评价 Vepdegestrant 与 PF-07220060 联合用药的总体安全性特征和耐受性。3. 评价 Vepdegestrant 与 PF-07220060 联合给药时，Vepdegestrant、ARV-473 和 PF-07220060 的血浆药物暴露量。4. 评估治疗后血浆 ctDNA 相对于基线水平的变化。II期探索性目的：1. 探索 PF-07220060 联合 Vepdegestrant 治疗对患者报告的症状和健康相关生命质量的影响。2. 了解乳腺癌的肿瘤生物学，确定潜在的敏感性和/或耐药性机制。3. 评价分子定义的研究参与者人群中突变状态与应答之间的关系。4. 探索药物基因组学对 PF-07220060 血浆药物暴露量的影响。

开始日期2024-11-18

申办/合作机构

Pfizer Inc.

[+2]

NCT06645938

/ Completed临床1期

A PHASE I, RANDOMIZED, OPEN-LABEL, 2-PERIOD, 2-TREATMENT, 2-SEQUENCE, CROSSOVER, SINGLE-DOSE STUDY IN HEALTHY ADULT PARTICIPANTS TO ESTIMATE THE BIOAVAILABILITY OF AN VARIANT (HIGH HARDNESS) TABLET OF VEPDEGESTRANT (ARV-471, PF-07850327) RELATIVE TO THE REGISTRATIONAL TABLET

The purpose of the study is to compare the amount vepdegestrant available from two different tablet formulations under fed conditions in healthy adult participants; 200 mg vepdegestrant alternative tablet formulation compared to 200 mg vepdegestrant standard tablet formulation.
This study is seeking male or female participants of non-childbearing potential age who:
* are 18 years or older
* are healthy as decided by medical tests.
* have a Body mass index (BMI) of 16 to 32 kilogram per meter squared; and a total body weight of more than 45 kilograms (99 pounds).
All participants will be put into groups to receive one of the 2 treatments in each period. This study will consist of 2 treatment sequences:
* Sequence 1: Single 200 mg dose of vepdegestrant registrational tablet in Period 1, followed by a single 200 mg dose of vepdegestrant variant tablet in Period 2.
* Sequence 2: Single 200 mg dose of vepdegestrant variant tablet in Period 1, followed by a single 200 mg dose of vepdegestrant registrational tablet in Period 2.
Participants will be in the study for about 11 weeks.

开始日期2024-10-16

申办/合作机构

Pfizer Inc.

[+1]

100 项与维普地司他相关的临床结果

登录后查看更多信息

100 项与维普地司他相关的转化医学

登录后查看更多信息

100 项与维普地司他相关的专利（医药）

登录后查看更多信息

项与维普地司他相关的文献（医药）

2025-11-01·CURRENT MEDICINAL CHEMISTRY

Analysis of the Main Directions in the Development of Mono and Combination Pharmacotherapy Acting on Hormonal Signaling Pathways of Breast Cancer According to the FDA Databases and Clinicaltrials.gov

Article

作者: Chubarev, Vladimir ; Abdullaeva, Sabina ; Liu, Junqi ; Samorodov, Alexandr ; Gabdrahimova, Renata ; Abdullaeva, Polina ; Samsonov, Mikhail ; Neganova, Margarita E. ; Sukocheva, Olga ; Nazmieva, Ksenia ; Smolyarchuk, Elena

Background::

Hormone signaling plays a significant role in cancerogenesis. This review presents a comprehensive analysis of FDA-approved drugs, as well as recent clinical trials of drugs acting on hormone signaling pathways. It discusses traditional methods of hormonal cancer therapy and identifies new mechanisms in cancer hormonal signaling. The review has made use of the databases Clinicaltrials.gov and PubMed to find new trends in the development of anti-cancer drugs and related hormonal-dependent mechanisms of breast cancer.

Methods::

A search of the Drugs@FDA database was conducted to identify pharmaceutical agents approved by the FDA for the treatment of hormone-dependent breast tumors. The clinical trials for these drugs were obtained from ClinicalTrials.gov. The search was expanded from 2018 to early 2024. The keywords used in the search for information were breast cancer, hormonal signaling pathways, luminal types of breast cancer, and hormone-dependent breast cancer. The drug targets, pharmacological information, and clinical data were obtained from the PubMed database.

Results::

An analysis of the ClinicalTrials.gov database revealed that the pharmacokinetic direction has significant potential for the discovery of new drugs. The metabolites of SERMs metabolites and their combination have the potential to enhance the efficiency of prodrug. Small molecules can penetrate through the blood-brain-barrier, making them a promising avenue for treating brain metastasis. New SERDs, such as ZB716, exhibit superior oral bioavailability compared to fulvestrant, which is solely administered via injection. The investigation of the signaling hormonal pathways of BC allows for the enhancement of personalised anti-cancer therapy and the overcoming of resistance. Consequently, the specific mechanism of action of ARV-471 (the PROTAC group) enhances sensitivity to drug-resistant targets and affects non-enzymatic functions. Furthermore, PROTACs exhibit markedly enhanced target selectivity in comparison to traditional inhibitors. The combination of endocrine therapy for breast cancer with compounds that target mTOR, PI3K, CDK4/6, and other pathways holds considerable promise. The combination of letrozole with everolimus demonstrated the most promising outcome, with a median progression-free survival period of 22 months, a significant improvement over the 9-month median progression-free survival observed in monotherapy with letrozole.

Conclusion::

It is evident that traditional endocrine treatments play a pivotal role in the management of HR+ BC. However, the emergence of resistance necessitates the development of novel therapeutic strategies. These strategies should be based on pharmacokinetics, further investigation of the molecular signaling pathways of BC, such as new SERMs, SERDs, PROTACs, as well as new drug groups, like SERCAs, CERANs, SHERPAs. Combination therapy represents the most promising avenue for BC treatment. While PROTAC combination with new monotherapeutic agents for BC treatment has yet to be investigated, we believe that such combinations have the potential to make the treatment more selective, effective, and personalised in the future.

2025-10-01·Nature Reviews Clinical Oncology

PROTAC SERD vepdegestrant outperforms fulvestrant for advanced-stage ER+HER2− breast cancer harbouring acquired ESR1 mutations

Article

作者: Han, Sileny N ; Neven, Patrick

2025-08-07·NEW ENGLAND JOURNAL OF MEDICINE

Vepdegestrant, a PROTAC Estrogen Receptor Degrader, in Advanced Breast Cancer

Article

作者: Parameswaran, Janaki ; Hu, Xichun ; Mouret-Reynier, Marie-Ange ; Jerzak, Katarzyna J. ; Lu, Dongrui R ; Patsouris, Anne ; Zhi, Xin ; Valota, Olga ; Guarneri, Valentina ; Cui, Jiuwei ; De Laurentiis, Michelino ; Sezer, Ahmet ; Jhaveri, Komal ; Yoshinami, Tetsuhiro ; Fontana, Andrea ; Cil, Timucin ; Zamagni, Claudio ; Martignoni, Marcella ; Molckovsky, Andrea ; Hamilton, Erika P. ; Ladoire, Sylvain ; Rodriguez-Lescure, Alvaro ; Zhang, Yongqiang ; Fuentes, Christian ; Demirci, Umut ; Campone, Mario ; Cazzaniga, Marina

BACKGROUND:

Vepdegestrant is an oral proteolysis-targeting chimera (PROTAC) estrogen receptor (ER) degrader that directly harnesses the ubiquitin-proteasome system.

METHODS:

In this phase 3, open-label, randomized trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had received one previous line of cyclin-dependent kinase 4 and 6 inhibitor therapy plus one line of endocrine therapy (and up to one additional line of endocrine therapy). Patients were randomly assigned in a 1:1 ratio to receive vepdegestrant at a dose of 200 mg orally once every day of each 28-day cycle or fulvestrant at a dose of 500 mg, administered intramuscularly, on day 1 and day 15 of cycle 1 and on day 1 of subsequent cycles, with randomization stratified according to ESR1-mutation status and presence or absence of visceral disease. The primary end point was progression-free survival as assessed by blinded independent central review among the patients with ESR1 mutations and among all the patients who underwent randomization. Progression-free survival was estimated with Kaplan-Meier methods and hazard ratios with a stratified Cox proportional-hazards model.

RESULTS:

A total of 624 patients underwent randomization; 313 were assigned to receive vepdegestrant, and 311 to receive fulvestrant. Among the 270 patients with ESR1 mutations, the median progression-free survival was 5.0 months (95% confidence interval [CI], 3.7 to 7.4) with vepdegestrant and 2.1 months (95% CI, 1.9 to 3.5) with fulvestrant (hazard ratio, 0.58 [95% CI, 0.43 to 0.78]; P<0.001). Among all the patients, the median progression-free survival was 3.8 months (95% CI, 3.7 to 5.3) with vepdegestrant and 3.6 months (95% CI, 2.6 to 4.0) with fulvestrant (hazard ratio, 0.83 [95% CI, 0.69 to 1.01]; P = 0.07). Adverse events of grade 3 or higher occurred in 23.4% of the patients in the vepdegestrant group and in 17.6% of the patients in the fulvestrant group. Adverse events led to treatment discontinuation in 2.9% and 0.7% of the patients, respectively.

CONCLUSIONS:

Among patients with ER-positive, HER2-negative advanced breast cancer, vepdegestrant was associated with significantly longer progression-free survival than fulvestrant in the subgroup with ESR1 mutations but not in the full patient population. (Funded by Pfizer and Arvinas Estrogen Receptor; VERITAC-2 ClinicalTrials.gov number, NCT05654623.).

334

项与维普地司他相关的新闻（医药）

2025-09-27

·丁香园 Insight 数据库

专家解读：告别一刀切，乳腺癌进入「分型而治」精准时代

乳腺癌是女性最常见、发病率最高的恶性肿瘤之一。公开数据显示，2022 年全球乳腺癌新发病例有 230 万，死亡病例有 67 万。同期中国新发病例数为 35.7 万，死亡病例数为 7.5 万。庞大的临床需求催生出了规模超千亿的市场，也吸引了国内外众多药企布局。 Insight 数据库显示，全球在研的乳腺癌新药超过 2000 款（仅统计积极状态）。而随着越来越多创新疗法涌现，乳腺癌的治疗也进入了「分型而治」的精准时代。2021 年至今，全球有 14 个乳腺癌新药获批上市，基本上都是针对具体基因分型的精准治疗药物，包括 HR 阳性/ HER2 阴性乳腺癌、三阴性乳腺癌等。 2021 年以来上市的乳腺癌新药来源：Insight 数据库整理另外，目前处于申请上市阶段的乳腺癌新药还有 5 款，包括瑞康曲妥珠单抗（恒瑞）、吉达利塞（辉瑞）、Vepdegestrant（Arvinas/辉瑞）、库莫西利（正大天晴）和博度曲妥珠单抗（科伦博泰）。这些精准治疗药物的上市，将进一步改变乳腺癌的临床实践格局。面对层出不穷的创新疗法，丁香园 Insight 数据库特邀湖南省肿瘤医院和湖南省第三人民医院共建肿瘤中心主任谢宁教授，围绕乳腺癌的三大分型，结合现有治疗指南，从临床角度分享：改变中国乳腺癌临床实践的进行时和不远将来时。 HR 阳性/HER2 阴性乳腺癌 HR 阳性/HER2 阴性是乳腺癌中最常见的亚型，约占 70%，其中 95% 的患者在首次确诊时为早期乳腺癌（EBC）。不过即使接受了标准内分泌治疗，部分 HR+/HER2- 早期乳腺癌患者仍存在较高的复发风险。因此针对早期乳腺癌，如何进一步降低复发风险、寻求更多治愈，成为了临床实践的主要目标。谢宁教授指出，目前临床研究证实 CDK4/6 抑制剂联合内分泌治疗可以显著延长 HR+/HER2- 早期乳腺癌高危患者的无浸润性肿瘤复发生存率（iDFS）。基于 MonarchE（阿贝西利）、NATALE（瑞波西利）和 DAWNA-A（达尔西利）等关键研究的阳性结果，该方案在国内外指南中也已经从晚期向早期推进。另外，CDK4/6 抑制剂在辅助治疗和新辅助治疗中也正在进行疗效和安全性的探索。针对晚期乳腺癌，当前 CDK4/6 在跨线治疗领域的研究已经非常丰富，临床可及性也处于较高水平，不过从实际治疗效果来看，仍存在一定提升空间。正大天晴的库莫西利是一款 CDK2/4/6 抑制剂，特异性更强，在 TQB3616-III-01 研究中已经展现出了显著的缓解和生存获益，mPFS 超过 16 个月。这款产品的出现，或许可以给晚期患者带来新的治疗选择。伊那利塞、卡匹色替等晚期乳腺癌新药，主要通过调节 PI3K-AKT-mTOR 通路发挥治疗作用。这类产品虽然在临床疗效上表现不俗，但高昂的治疗成本始终制约着它们的广泛应用。另外，ER 靶向药物、TROP2 ADC、HER3 ADC、EGFR/HER3 ADC 等在 HR 阳性/HER2 阴性乳腺癌中也都显示出了良好的疗效和安全性。限于篇幅，本文不再一一赘述，详情可查看直播回放视频（链接见文章结尾）。谢宁教授强调，正是因为药物选择越来越多，医生更要慎之又慎，同时高度重视安全性和不良反应的管理。 HER2 阳性乳腺癌 & 三阴性乳腺癌 HER2 阳性乳腺癌约占所有乳腺癌的 14%，其侵袭性较强，且发生脑转移概率较高。目前这类乳腺癌的治疗已经从单一化疗策略发展为了以靶向治疗为核心的综合治疗策略。靶向药物中，单克隆抗体（如曲妥珠单抗、帕妥珠单抗）、酪氨酸激酶抑制剂（TKI，如拉帕替尼、图卡替尼）等可以有效 HER2 阳性乳腺癌患者的生存预后，已被国内外指南纳入标准治疗推荐。近年来，以德曲妥珠单抗为代表的 ADC 陆续获批，又为患者提供了全新的治疗选择。谢宁教授表示，HER2 ADC 研究正深刻影响着中国乳腺癌的临床实践。结合现有的研究数据，德曲妥珠单抗（T-DXd）和瑞康曲妥珠单抗（SHR-1811）或许会是未来最值得期待的两款 HER2 ADC，它们的适应症覆盖新辅助、辅助、晚期一线、晚期后线等多个治疗场景。三阴性乳腺癌是指 ER、PR、HER2 表达均为阴性的一类乳腺癌，由于缺乏明确的治疗靶点，此前治疗进展一直比较缓慢，直到近些年 PARP 抑制剂、PD1、ADC 等靶向新药相继获批，才有所改善。针对早期三阴性乳腺癌，谢宁教授详细介绍了帕博利珠单抗、替雷利珠单抗、卡瑞利珠单抗新辅助治疗的临床研究设计和阳性结果。在晚期三阴性乳腺癌中，多项联合治疗方案已展现出显著疗效：例如氟唑帕利联合阿帕替尼（FABULOUS 研究）、特瑞普利单抗联合白蛋白紫杉醇（TORCHLIGHT 研究）等，不仅能有效延长患者的无进展生存期（PFS），目前也已在临床中获得广泛应用。此外，针对晚期三阴性乳腺癌的更多创新治疗方案研究正持续推进，包括双抗、ADC、ADC +免疫、抗血管+免疫、双免等，这些未来有望进一步突破现有治疗瓶颈，为晚期三阴性乳腺癌临床治疗格局带来新的改变。如欲了解本次线上讲堂的更多详细内容，请扫描下方二维码👇，观看直播回放。封面来源：站酷海洛免责声明：本文仅作信息分享，不代表 Insight 立场和观点，也不作治疗方案推荐和介绍。如有需求，请咨询和联系正规医疗机构。编辑：月牙 PR 稿对接：微信 insightxb 投稿：微信 insightxb；邮箱 insight@dxy.cn

上市批准临床结果

2025-09-25

·Firstwordpharma

Lilly's oral SERD wins FDA approval in ESR1-mutant breast cancer

Eli Lilly's oral selective oestrogen receptor degrader (SERD) Inluriyo (imlunestrant) was greenlit by the FDA on Thursday for certain patients with breast cancer, beating several other SERD developers to the punch. The drug will be available in the US "in the coming weeks," according to the pharma.Inluriyo can be used to treat adults with ER-positive, HER2-negative, ESR1-mutated, second-line advanced or metastatic breast cancer. The agency also cleared Guardant Health's Guardant360 CDx assay as a companion diagnostic to identify breast cancer patients with ESR1 mutations.The approval was based on data from the Phase III EMBER-3 trial, which were reported at the San Antonio Breast Cancer Symposium (SABCS) last December. Results from the study showed that Inluriyo reduced the risk of progression or death by 38% over standard endocrine therapy in ESR1-mutant patients, with median progression-free survival (PFS) of 5.5 months versus 3.8 months for the comparator.Investors were more excited, however, by findings in a separate EMBER-3 cohort that gave patients Inluriyo in combination with Lilly's CDK4/6 inhibitor Verzenio (abemaciclib). The duo achieved a median PFS of 9.4 months, reducing the risk of progression or death by 43% compared to the SERD alone — and the benefit was seen regardless of ESR1 or PI3K pathway mutation status, including in patients who had previously received CDK4/6 inhibitors (see – KOL Views Q&A: Battle for oral SERD supremacy in HR+ breast cancer boils down to efficacy). A spokesperson for Lilly told FirstWord that the combination arm of the study began later than the monotherapy arm, and its results are still maturing. The pharma has completed an updated analysis, which will be shared with the FDA and presented at a medical meeting later this year.Still, results from a recent FirstWord poll of 100 US and European oncologists suggest doctors are still eager to prescribe Inluriyo monotherapy. Nearly 75% of respondents said they are 'very' or 'extremely' likely to prescribe Lilly's oral SERD to ESR1-mutated patients in the second-line setting (see – Physician Views In-Depth: Oral SERDs on track to transform 2L care of ER+/HER2- breast cancer).Inluriyo is also being evaluated as an adjuvant treatment in the 8000-patient Phase III EMBER-4 trial in patients with ER-positive, HER2-negative early breast cancer at increased risk of recurrence.The SERD spaceThe monotherapy approval is a key regulatory win for Lilly, but several other drugmakers are racing toward the SERD finish line. At this year's American Society of Clinical Oncology (ASCO) meeting, Lilly further fleshed out its use case for Inluriyo with safety results and patient-reported outcomes from EMBER-3, while AstraZeneca presented data on its rival SERD, camizestrant, in the Phase III SERENA-6 study.While AstraZeneca reported a superior PFS of 16 months, the company used serial biopsies to painstakingly predict ESR1 mutations and initiate therapy with camizestrant earlier in soon-to-be progressing patients who were already on a CDK4/6 inhibitor. The pinpoint precision contrasts with the broad activity seen with Lilly's Inluriyo-plus-Verzenio all-comers strategy Eli Lilly said it sees broad activity in an all-comers population in ER-positive/HER-negative breast cancer, while AstraZeneca used serial liquid biopsies to painstakingly predict ESR1 mutations and initiate therapy earlier in soon-to-be progressing patients.Jacob Van Naarden, EVP and President of Lilly Oncology, told FirstWord at the time that the patient burden of serial blood testing — financial, logistical and mental — sets a high bar for efficacy. For more from that interview, see Spotlight On: Pushback on AstraZeneca's new oral SERD strategy that 'doesn't really make a lot of sense'.Another oral SERD candidate is Roche's giredestrant, which recently impressed in the Phase III evERA study when given in combination with everolimus. The duo showed significant and clinically meaningful improvements on PFS in both patients with ESR1 mutations and the intention-to-treat population compared with endocrine therapy plus everolimus.And while Pfizer and Arvinas' oral PROTAC oestrogen receptor degrader vepdegestrant is under review at the FDA, the partners last week decided to step back from the programme and search for a third party to handle its commercialisation.

临床结果临床3期ASCO会议上市批准

2025-09-24

·药明康德

同行致远 | 抗癌分子胶疾病控制率超90%；PROTAC®冲刺全球首批 | Bilingual

编者按：诱导接近（induced proximity）机制通过将蛋白或核酸拉近形成复合体，从而调控靶点功能。基于这一机制开发的靶向蛋白降解剂（TPD）已成为新药研发的热点之一。与传统抑制剂不同，它们无需直接抑制靶蛋白活性，而是通过降解疾病相关蛋白，有望靶向许多长期被认为“不可成药”的靶点。药明康德在TPD技术刚刚起步时，就开始布局相关能力和技术，积累了丰富的成功经验，搭建起集发现、合成、分析纯化和测试等能力于一体的一站式赋能平台。目前，该平台已成功支持超过120款TPD分子的开发，其中20余款顺利推进至临床阶段。近年来，基于诱导接近机制的研发已不再局限于TPD，还扩展至针对难以成药靶点的抑制剂开发，以及组织特异性药物的开发。本文将回顾2025年第三季度该领域的最新进展，并介绍药明康德的一体化CRDMO平台如何高效解决诱导接近药物开发过程中的诸多挑战。靶向蛋白降解：FDA受理PROTAC®疗法新药申请 Arvinas与辉瑞（Pfizer）宣布，美国FDA已受理为PROTAC®疗法vepdegestrant递交的新药申请（NDA），用于治疗既往接受过内分泌治疗、雌激素受体阳性（ER+）/人表皮生长因子受体2阴性（HER2-）且伴有ESR1突变的晚期或转移性乳腺癌患者。根据新闻稿，vepdegestrant是首个在乳腺癌患者中展现临床获益的PROTAC®疗法。若获批，该药物将成为首个获美国FDA批准的PROTAC®雌激素受体降解剂。除了Arvinas公司，C4 Therapeutics公司还公布了靶向IKZF1/3的在研蛋白降解疗法cemsidomide治疗多发性骨髓瘤患者的1期临床试验结果。截至2025年7月23日，75 µg剂量组的客观缓解率（ORR）为40%，100 µg剂量组的ORR为50%。该公司计划在2026年初启动注册性临床试验。 Monte Rosa Therapeutics公司开发的靶向NEK7的分子胶蛋白降解剂MRT-8102，在1期临床试验中已完成首例患者给药。这款口服选择性分子胶降解剂有望用于治疗与NLRP3、IL-1β和IL-6失调相关的炎症性疾病。值得注意的是，该公司还在《科学》杂志发表论文，详细介绍了其自主开发的人工智能（AI）和机器学习（ML）引擎如何发现可通过CRBN介导降解的人体蛋白，涵盖多种不同的蛋白结构域与类别。这一突破显著拓展了分子胶蛋白降解药物的可操作靶点空间。该公司还在9月15日宣布与诺华（Novartis）达成57亿美元的新研发合作协议，携手推动针对免疫介导疾病的创新降解剂研发。 TPD药物虽具广阔前景，但其开发也面临独特挑战。例如，PROTAC®分子由于分子量大、结构复杂，通常存在溶解度差和药代动力学性质不佳的问题。以下案例展示了药明康德旗下合全药业（WuXi STA）如何与合作伙伴携手，有效应对这些挑战。解决TPD药物开发痛点，加速创新疗法进入临床试验几年前，一家公司因PROTAC®分子的生产难题，选择与合全药业合作，希望在14个月内完成候选药物的生产，以支持IND申请及首次人体临床试验。然而，该候选分子的初始合成路线非常复杂，需要多达24个步骤，且最终产率仅为0.3%。此外，PROTAC®特定的分子结构进一步增加了产品结晶和纯化难度。同时，由于候选化合物分子量较大且水溶性低，其口服生物利用度只有0.9%。值得注意的是，在合成过程中还有三步涉及使用罕见金属钯（Pd）作为催化剂，这不仅带来潜在安全隐患，更显著提高了生产成本。针对上述问题，合全药业的工艺研发、生物催化及结晶工艺等团队协同攻关，重新设计了一条合成路线，将合成步骤从原来的24步缩减至16步，并在其中两个步骤中用生物催化剂替代了钯催化剂。为攻克结晶难题，团队采用高通量结晶筛选技术，迅速确定了符合纯度与产量要求的结晶工艺，并通过优化大幅提升了生产过程的总产率。这些改进不但极大提高了整体合成工艺的可放大性，也提升了合成效率并降低了成本。与此同时，合全药业的制剂研发团队针对药物口服生物利用度低的问题，进行了全面的生物利用度增强技术筛选，最终选定喷雾干燥制备固体分散体（SDD）技术进行制剂制备。这种技术将难溶药物以无定形状态高度分散在聚合物中，目前已成功应用于多种上市药物的制剂开发中。借助SDD技术，候选化合物药片制剂的口服生物利用度提高了约30倍，为后续临床应用奠定了坚实基础。合全药业一体化CRDMO平台的整合能力，使多个团队能够并行推进原料药与制剂开发，高效协作，加速破解PROTAC®分子开发中的难题。最终，团队仅用了12个月就完成了支持IND申请所需的候选药物生产和制剂制备，顺利供应首次人体临床研究用药，比合作伙伴原定时间提前了2个月。超越蛋白降解：分子胶抑制剂获突破性疗法认定 TPD只是诱导接近机制在新药开发中的一种应用。分子胶通过将靶点蛋白与呈递蛋白（presenter proteins）结合，形成复合表面，从而突破传统药物对活性位点的依赖，让小分子能够靶向更多“不可成药”的靶点，显著拓展了治疗可能性。例如，Revolution Medicines公司研发的RAS抑制剂elironrasib成功招募了cyclophilin这一呈递蛋白，实现了对激活状态下KRAS G12C蛋白的特异性靶向与抑制。今年7月，该药物获得FDA授予的突破性疗法认定，用于治疗携带KRAS G12C突变的非小细胞肺癌（NSCLC）患者。Elironrasib单药治疗在既往未接受KRAS抑制剂的经治NSCLC患者中达到56%的ORR和94%的疾病控制率（DCR）；与pembrolizumab联用时，一线治疗的ORR更是高达100%，显示出可喜的初步疗效。 Halda Therapeutics公司的调节诱导接近靶向嵌合体（RIPTAC）则代表另一种新策略。这类异双功能分子的一端结合富集于癌细胞中的靶点蛋白，另一端结合细胞生存必需的关键蛋白。当细胞同时表达这两种蛋白时，RIPTAC分子将两者结合形成复合体，使关键蛋白失活，从而诱导癌细胞死亡。今年8月，Halda Therapeutics宣布与VantAI达成研发合作，利用VantAI的人工智能和结构蛋白组学发现平台，开发治疗癌症和免疫疾病的下一代RIPTAC药物。越来越多开发诱导接近药物的公司开始利用人工智能技术加速新药发现，除了Halda Therapeutics与VantAI的合作，Revolution Medicines在7月与Iambic Therapeutics也达成研发合作，利用Iambic公司基于AI的蛋白-配体结构预测模型和图像神经网络模型来发现创新候选药物。今年8月，致力于分子胶药物开发的Proxygen宣布与洛桑联邦理工学院（EPFL）建立战略研究合作关系。这一合作旨在将高通量体外筛选与先进计算设计相结合，以系统性地预测和验证新底物-连接酶相互作用，并设计能够诱导靶向蛋白降解的化学分子。非降解性分子胶的开发也得到投资人的关注。今年9月，Rapafusyn Pharmaceuticals宣布完成4400万美元A轮融资。该公司的RapaGlue平台已展现出生成高协同非降解型分子胶的能力，这些分子胶具有较高的细胞膜通透性，可用于调控蛋白-蛋白相互作用、转录因子、转运蛋白、离子通道、酶等多种难以成药靶点。一体化平台助力分子胶早期发现药明康德一体化平台的能力不但涵盖PROTAC®，还包括分子胶、以及多种新兴双功能分子。以分子胶药物发现为例，其早期研发阶段中无偏倚药物筛选的低命中率始终是一大挑战。为助力合作伙伴有效应对这一难题，药明康德采取了“双轨并进”的策略，构建起一套兼顾广度与深度的化合物库体系：一方面，通过多样化的DNA编码化合物库（DEL）大范围探索新靶点；另一方面，借助聚焦化合物库精细化研究已知蛋白体系，提升发现效率。 ▲药明康德分子胶发现平台（图片来源：参考资料[15]）在分子胶药物的早期发现过程中，药明康德不仅依赖DNA编码化合物库进行筛选，还不断引入并整合多种先进技术，以助力合作伙伴拓展分子胶药物的发现能力。其中，亲和筛选质谱（ASMS）提供无标记筛选手段。药明康德构建了一个涵盖超过37万个小分子的广谱化合物库，通过比较这些分子在单蛋白与双蛋白条件下的质谱信号差异，精准识别出能够促进蛋白–蛋白相互作用的潜在分子胶候选物，从而识别出潜在促互作的小分子。与此同时，公司还部署高通量筛选（HTS）技术。在“一孔一化合物”的自动化运行模式下，结合蛋白结合能力或降解能力等功能性实验，HTS能迅速锁定具备生物活性的候选分子，大幅提升筛选效率与准确性。通过将ASMS与HTS等多维筛选工具与DEL平台深度融合，药明康德打破了单一筛选方式的限制，让更多不同类型的靶点进入分子胶研究视野，进一步拓宽了分子胶在多类靶点上的研发空间。展望未来 Broad研究所联合创始人Stuart Schreiber博士在2024年发表的一篇评论文章中指出，基于诱导接近作用的分子胶和双功能化合物为药物发现提供了创新模式。这一模式可以通过新颖的方式调控具有挑战性的靶点，包括稳定、降解、易位、激活，以及重塑转录回路。对于精准医疗而言，这可能提供了一个独特的机会，将“合适的药物在合适的时间、用于合适的患者，在合适的组织中生效”这一理念变为现实。药明康德将继续秉持“让天下没有难做的药，难治的病”的愿景，依托全球研发基地与生产网络，以独特的一体化、端到端的CRDMO模式，助力包括靶向蛋白降解剂在内的诱导接近药物的开发，帮助合作伙伴将科学创新转化为惠及全球患者的变革性药物。 CRDMO: Q3 2025 Review of Induced Proximity Drugs The induced proximity mechanism regulates target function by bringing proteins or nucleic acids into close proximity to form complexes. Targeted protein degraders (TPDs) developed on this basis have become one of the hottest areas in drug discovery. Unlike traditional inhibitors, TPDs do not need to block target activity directly; instead, they eliminate disease-related proteins, opening opportunities to tackle many proteins once deemed “undruggable.” When TPD technology was still in its infancy, WuXi AppTec started building relevant capabilities. Since then, the company has established a comprehensive, integrated platform encompassing discovery, synthesis, purification, analysis, and testing. To date, this platform has supported the development of more than 120 TPD molecules, with over 20 advancing to clinical stages. In recent years, induced proximity has extended beyond TPDs to include inhibitors for hard-to-drug targets and tissue-specific therapies. This article reviews the latest developments in Q3 2025 and highlights how WuXi AppTec’s integrated CRDMO platform helps overcome the unique challenges of developing induced-proximity medicines. Targeted Protein Degradation: FDA Accepts NDA for a PROTAC® Therapy In a major regulatory milestone, Arvinas and Pfizer announced that the U.S. FDA has accepted the New Drug Application (NDA) for the PROTAC® therapy vepdegestrant. The application covers patients with advanced or metastatic breast cancer who have received prior endocrine therapy and are ER+/HER2− with ESR1 mutations. According to the companies, vepdegestrant is the first PROTAC® therapy to demonstrate clinical benefit in breast cancer. If approved, it will become the first FDA-approved PROTAC® estrogen receptor degrader. Other companies are also making progress. C4 Therapeutics reported Phase 1 clinical results for its protein degrader cemsidomide in multiple myeloma. As of July 23, 2025, the objective response rate (ORR) was 40% in the 75 µg cohort and 50% in the 100 µg cohort. A registrational trial is planned for early 2026. Meanwhile, Monte Rosa Therapeutics announced that the first subjects have been dosed in a Phase 1 study evaluating MRT-8102, a NEK7-directed molecular glue degrader being developed for the treatment of inflammatory conditions driven by the NLRP3 inflammasome, IL-1β, and IL-6. Adding to this progress, Monte Rosa published a paper in Science describing how its proprietary AI and ML engine identified human proteins potentially amenable to CRBN-mediated degradation. The findings, spanning diverse protein domains and classes, significantly broaden the actionable target space for molecular glue degrader discovery. On September 15, the company also announced an agreement to collaborate with Novartis to develop novel degraders for immune-mediated diseases. While clinical advances are encouraging, TPDs still pose unique development hurdles. For example, due to their large molecular weight and structural complexity, PROTAC® compounds often suffer from poor solubility and suboptimal pharmacokinetics. The following case study illustrates how WuXi STA, an integral part of WuXi AppTec, collaborated with a partner to address these challenges effectively. Addressing Key Bottlenecks in TPD Drug Development Several years ago, a biotech company developing a PROTAC® candidate faced synthetic challenges and turned to WuXi STA for support. The goal was to complete the production of drug substance and clinical trial material within 14 months to support an IND filing and FIH trial. However, the original synthesis route involved 24 steps and yielded only 0.3%. Crystallization and purification proved difficult due to the compound’s unique structure. Compounding the challenge, the candidate’s high molecular weight and poor solubility resulted in oral bioavailability of only 0.9%. Moreover, three steps in the synthesis relied on a palladium (Pd) catalyst, raising safety concerns and increasing production costs. To resolve these issues, WuXi STA’s process chemistry, biocatalysis, and crystallization teams worked in concert to redesign the synthesis route, reducing the number of steps from 24 to 16 and replacing palladium with biocatalysts in two steps. To tackle crystallization bottlenecks, high-throughput crystallization screening identified suitable conditions that met both purity and yield requirements. These changes significantly improved the scalability and efficiency of the synthetic route while reducing costs. Simultaneously, WuXi STA’s formulation team addressed the low oral bioavailability by exploring a range of enabling technologies and ultimately selected spray-dried dispersion (SDD) to prepare a solid dosage form. SDD disperses poorly soluble compounds in an amorphous state within a polymer matrix and has been successfully used in several approved drugs. With this approach, the candidate’s oral bioavailability improved by approximately 30-fold—supporting further clinical advancement. Thanks to WuXi STA’s integrated CRDMO model, API process development and formulation were advanced in parallel by multiple teams working seamlessly together. Ultimately, they delivered IND-enabling materials and clinical trial materials within just 12 months—two months ahead of schedule. Beyond Protein Degradation: Molecular Glue Inhibitor Receives Breakthrough Designation Induced proximity is not limited to protein degradation. Molecular glues, which bind a target protein and a presenter protein to form composite binding surfaces, bypass the need to interact with active sites. This allows small molecules to reach a broader range of targets, including those once considered undruggable. A notable example comes from Revolution Medicines. Its RAS inhibitor elironrasib recruited cyclophilin as a presenter protein to selectively target and inhibit active-state KRAS G12C. In July, the FDA granted Breakthrough Therapy Designation for elironrasib in KRAS G12C-mutant NSCLC. Phase 1 data were compelling: in previously treated patients without prior KRAS inhibitors, monotherapy achieved a 56% ORR and 94% disease control rate (DCR). In combination with pembrolizumab as first-line therapy, the ORR reached 100%, signaling strong early potential. Halda Therapeutics is advancing another strategy with Regulated Induced Proximity Targeting Chimeras (RIPTACs). These heterobifunctional molecules bind a cancer-enriched target protein on one end and an essential survival protein on the other. By bringing the two together, RIPTACs inactivate the survival protein, triggering cancer cell death. In August, Halda announced a partnership with VantAI to apply AI and structural proteomics in the discovery of next-generation RIPTACs for cancer and immune diseases. Revolution Medicines also entered a collaboration with Iambic Therapeutics in July, leveraging AI-based protein-ligand prediction and neural network models to accelerate novel candidate discovery. In August, Proxygen announced a strategic research collaboration with EPFL (the Swiss Federal Institute of Technology in Lausanne). The collaboration aims to build a next-generation discovery paradigm that bridges high-throughput in vitro screening with state-of-the-art in silico design. Non-degrading molecular glues also attracted investors’ attention. In September, Rapafusyn Pharmaceuticals announced the closing of its oversubscribed Series A financing round ($44 million). Its RapaGlue platform has demonstrated the ability to create highly cooperative non-degrading molecular glues with high cell membrane permeability to modulate protein–protein interactions, transcription factors, transporters, ion channels, enzymes, and others. WuXi AppTec’s integrated platform supports not only PROTAC® development but also molecular glues and other bifunctional modalities. By uniting cutting-edge screening technologies, tailored library design, and deep scientific expertise, WuXi AppTec offers a fully integrated platform for molecular glue discovery. This approach supports partners across: Hit identification and validation Mechanistic characterization and degradation profiling Lead optimization and SAR development Outlook Looking ahead, the potential of induced proximity continues to grow. In a 2024 commentary, Dr. Stuart Schreiber, co-founder of the Broad Institute, highlighted molecular glues and bifunctional compounds as an innovative paradigm in drug discovery—capable of stabilizing, degrading, translocating, activating targets, as well as rewiring transcriptional circuits. For precision medicine, this may enable the long-sought goal of delivering “the right drug to the right patient at the right time—and in the right tissue.” Guided by its vision that “every drug can be made and every disease can be treated”, WuXi AppTec remains committed to leveraging its unique, fully integrated, end-to-end CRDMO model to help partners transform scientific innovation into transformative therapies for patients worldwide. 参考资料： [1] Arvinas Announces FDA Acceptance of the New Drug Application for Vepdegestrant for the Treatment of ESR1m, ER+/HER2- Advanced Breast Cancer. Retrieved August 20, 2025, from https://www.globenewswire.com/news-release/2025/08/08/3130368/0/en/Arvinas-Announces-FDA-Acceptance-of-the-New-Drug-Application-for-Vepdegestrant-for-the-Treatment-of-ESR1m-ER-HER2-Advanced-Breast-Cancer.html [2] C4 Therapeutics Reports Second Quarter 2025 Financial Results and Recent Business Highlights. Retrieved August 20, 2025, from https://ir.c4therapeutics.com/news-releases/news-release-details/c4-therapeutics-reports-second-quarter-2025-financial-results [3] Monte Rosa Announces Publication in Science of Key Insights that Enable Next Generation Molecular Glue Degrader Medicines. Retrieved August 20, 2025, from https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-announces-publication-science-key-insights-enable [4] Monte Rosa Therapeutics Announces First Subjects Dosed in Phase 1 Study of MRT-8102, a NEK7-Directed Molecular Glue Degrader for the Treatment of Multiple Inflammatory Diseases. Retrieved August 20, 2025, from https://ir.monterosatx.com/news-releases/news-release-details/monte-rosa-therapeutics-announces-first-subjects-dosed-phase-1 [5] SEED Therapeutics Named Finalist for 2025 Prix Galien USA “Best Start-Up” Award. Retrieved August 20, 2025, from https://seedtherapeutics.com/seed-therapeutics-named-finalist-for-2025-prix-galien-usa-best-start-up-award/ [6] Revolution Medicines Announces FDA Breakthrough Therapy Designation for Elironrasib. Retrieved August 20, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-fda-breakthrough-therapy-0 [7] Revolution Medicines Announces Publication of a Peer-Reviewed Research Paper in Science on the Discovery and Development of Zoldonrasib, a RAS(ON) G12D-Selective Inhibitor. Retrieved August 20, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-announces-publication-peer-reviewed [8] VantAI and Halda Therapeutics Forge Alliance to Discover Next-Generation RIPTAC Medicines. Retrieved August 20, 2025, from https://haldatx.com/vantai-and-halda-therapeutics-forge-alliance-to-discover-next-generation-riptac-medicines/ [9] Arvinas Reports Second Quarter 2025 Financial Results and Provides Corporate Update. Retrieved August 20, 2025, from https://ir.arvinas.com/news-releases/news-release-details/arvinas-reports-second-quarter-2025-financial-results-and [10] Targeted Protein Degrader. Retrieved August 20, 2025, from https://rcs.wuxiapptec.com/wp-content/uploads/RCS_Targeted-Protein-Degrader_20250818.pdf [11] Revolution Medicines and Iambic Announce Technology and Research Collaboration Using Iambic’s AI Discovery Tools to Pursue New Drug Candidates. Retrieved August 27, 2025, from https://ir.revmed.com/news-releases/news-release-details/revolution-medicines-and-iambic-announce-technology-and-research [12] Schreiber (2024). Molecular glues and bifunctional compounds: Therapeutic modalities based on induced proximity. Cell Chemical Biology, DOI: 10.1016/j.chembiol.2024.05.004 [13] Rapafusyn Pharmaceuticals Closes Over-Subscribed $44 Million Series A Financing to Advance Its Non-Degrading Molecular Glue Drug Discovery Platform. Retrieved September 11, 2025, from https://www.globenewswire.com/news-release/2025/09/04/3144896/0/en/Rapafusyn-Pharmaceuticals-Closes-Over-Subscribed-44-Million-Series-A-Financing-to-Advance-Its-Non-Degrading-Molecular-Glue-Drug-Discovery-Platform.html [14] Proxygen and EPFL Launch Strategic Collaboration to Advance AI-Driven Glue Discovery. Retrieved September 11, 2025, from https://www.globenewswire.com/news-release/2025/08/26/3139189/0/en/Proxygen-and-EPFL-Launch-Strategic-Collaboration-to-Advance-AI-Driven-Glue-Discovery.html [15] Molecular Glues Discovery: Challenges and Opportunities. Retrieved July 4, 2025 from https://wuxibiology.com/resource/discovery-of-molecular-glues-challenges-and-opportunities/ 免责声明：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：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

蛋白降解靶向嵌合体临床1期临床结果细胞疗法

100 项与维普地司他相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
ER阳性/HER2阴性/ESR1突变乳腺癌	申请上市	美国	Arvinas, Inc.	2025-06-06
ER阳性/HER2阴性乳腺癌	临床3期	美国	Arvinas Estrogen Receptor, Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	美国	Pfizer Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	中国	Arvinas Estrogen Receptor, Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	中国	Pfizer Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	日本	Arvinas Estrogen Receptor, Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	日本	Pfizer Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	阿根廷	Pfizer Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	阿根廷	Arvinas Estrogen Receptor, Inc.	2023-03-03
ER阳性/HER2阴性乳腺癌	临床3期	澳大利亚	Arvinas Estrogen Receptor, Inc.	2023-03-03

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05549505 (CTgov)	临床2期	ER阳性/HER2阴性乳腺癌	152	Surgical resection of breast tumor+ARV-471 (Arm A: ARV-471 (Experimental))	範簾簾範製鹽醖廠鬱鹽 = 醖醖衊選構製齋窪艱鏇構鑰構醖膚製襯淵夢構 (壓鑰憲網積遞構鬱選遞, 艱餘餘淵築鹹鬱糧醖構 ~ 範夢構壓蓋齋糧積鹹蓋) 更多	-	2025-08-29
				Surgical resection of breast tumor+anastrozole (Arm B: Anastrozole)	範簾簾範製鹽醖廠鬱鹽 = 築鏇齋膚夢遞窪襯襯壓構鑰構醖膚製襯淵夢構 (壓鑰憲網積遞構鬱選遞, 範積夢遞廠廠憲鑰選艱 ~ 齋餘築鬱夢鑰鬱構醖築) 更多
NCT05654623 (VERITAC-2, Pubmed \| N Engl J Med)	临床3期	晚期乳腺癌	624	Vepdegestrant 200 mg	廠製積餘鑰餘廠獵艱糧(淵簾糧願構鏇製艱餘蓋) = in 2.9% and 0.7% of the patients, respectively 構遞醖糧膚範襯襯繭壓 (糧衊鏇鏇選鹹廠衊糧遞 ) 更多	积极	2025-08-07
				Fulvestrant 500 mg
NCT05654623 (VERITAC-2, ASCO2025 \| Company_Website) 人工标引	临床3期	ER阳性/HER2阴性乳腺癌 ER Positive \| HER2 Negative	624	Vepdegestrant	範淵膚範獵網鏇遞鬱窪(遞網齋獵製築膚衊鬱製) = 膚網繭積觸積範範選廠夢夢窪衊廠積遞選齋顧 (築鬱鏇窪蓋鏇糧製鑰壓, 3.6–5.3) 更多	积极	2025-05-30
				fulvestrant	範淵膚範獵網鏇遞鬱窪(遞網齋獵製築膚衊鬱製) = 夢蓋製憲蓋蓋窪觸餘鏇夢夢窪衊廠積遞選齋顧 (築鬱鏇窪蓋鏇糧製鑰壓, 2.2–3.8) 更多
NCT05654623 (VERITAC-2, Company_Website) 人工标引	临床3期	ER阳性/HER2阴性乳腺癌 ESR1 Mutation	-	Vepdegestrant (ESR1 mutant)	獵蓋鑰繭築襯蓋糧製網(構鑰鏇壓衊鏇範顧選糧) = The results exceeded the pre-specified target hazard ratio of 0.60 in the ESR1m population. The trial did not reach statistical significance in improvement in PFS in the intent-to-treat (ITT) population. 觸鏇壓鏇廠艱積窪範願 (鏇衊簾遞齋醖襯繭製顧 )	不佳	2025-03-11
				fulvestrant (ESR1 mutant)
NCT05548127 (TACTIVE-U, GlobeNewswire) 人工标引	临床1期	ER阳性/HER2阴性乳腺癌三线	16	Vepdegestrant + Abemaciclib	顧淵壓醖顧構選鏇簾鑰(繭範範簾醖醖製構齋衊) = None 觸憲築築膚繭獵獵獵蓋 (襯鬱艱鹽鑰襯顧鏇顧蓋 ) 更多	积极	2024-12-10
				Vepdegestrant + Abemaciclib (mutant ESR1)
NCT05463952 (Pubmed \| Int J Clin Oncol)	临床1期	局部晚期不能切除的乳腺癌 \| 乳腺癌 \| ER阳性乳腺癌 ... estrogen receptor (ER) 更多	6	Vepdegestrant 200 mg QD	鑰簾構衊廠積夢遞蓋齋(遞鬱積構糧遞淵艱築淵) = Four (66.7%) patients experienced adverse events; none led to dose reduction or discontinuation 鑰簾膚衊繭構築襯餘淵 (繭蓋餘襯蓋製淵範積願 ) 更多	-	2024-11-20
NCT05538312 (CTgov)	临床1期	-	12	ARV-471 (Period 1: ARV-471 200 mg)	願壓廠夢壓醖範醖範鏇(鹹糧夢蓋憲窪醖衊糧顧) = 襯餘遞網網鏇觸壓鏇繭構選膚繭膚簾鬱願膚艱 (構蓋繭鏇積淵窪醖衊淵, 23) 更多	-	2024-09-23
				Itraconazole+ARV-471 (Period 2: ARV-471 200 mg + Itraconazole 200 mg)	願壓廠夢壓醖範醖範鏇(鹹糧夢蓋憲窪醖衊糧顧) = 鬱製鑰觸構衊糧鹽夢壓構選膚繭膚簾鬱願膚艱 (構蓋繭鏇積淵窪醖衊淵, 24) 更多
NCT05463952 (CTgov)	临床1期	局部晚期不能切除的乳腺癌 \| 乳腺癌 \| ER阳性乳腺癌 ... 更多	6	ARV-471	積獵範淵糧選鑰製餘醖 = 鹹顧鏇廠範鬱遞壓積淵鹽淵願鹽廠蓋糧顧獵餘 (鹹觸範願餘鹹窪壓願鹽, 範範鹽鬱餘襯願壓襯憲 ~ 餘願範選憲觸餘鏇蓋蓋) 更多	-	2024-09-23
NCT05673889 (CTgov)	临床1期	-	24	Dabigatran (Period 1: Dabigatran 75 mg)	簾願遞襯選夢鬱鏇簾顧(簾膚鏇願鬱構廠鹽廠選) = 積鏇壓簾糧積觸簾膚範蓋廠襯襯鹽觸積醖醖膚 (衊憲鑰襯網鹹觸遞糧餘, 94) 更多	-	2024-08-16
				ARV-471+Dabigatran (Period 2: Dabigatran 75 mg + ARV-471 200 mg)	簾願遞襯選夢鬱鏇簾顧(簾膚鏇願鬱構廠鹽廠選) = 繭齋獵鏇餘淵簾鹹願糧蓋廠襯襯鹽觸積醖醖膚 (衊憲鑰襯網鹹觸遞糧餘, 66) 更多
NCT05652660 (CTgov)	临床1期	-	12	Rosuvastatin (Period 1: Rosuvastatin)	糧顧顧膚齋鏇獵觸鹹憲(鹽繭膚獵鏇網憲構願鹹) = 淵膚齋遞範餘製憲憲淵範網餘構壓製製夢構淵 (觸鑰齋淵鑰衊鹽廠願觸, 53) 更多	-	2024-07-26
				Rosuvastatin+ARV-471 (Period 2: ARV-471 + Rosuvastatin)	糧顧顧膚齋鏇獵觸鹹憲(鹽繭膚獵鏇網憲構願鹹) = 艱醖鏇艱製鬱簾淵膚遞範網餘構壓製製夢構淵 (觸鑰齋淵鑰衊鹽廠願觸, 48) 更多