A Randomized, Open-label, Phase III Study of SIM0270 Combined With Everolimus Versus Treatment of Physician's Choice in Patients With CDK4/6 Inhibitors Previously Treated , ER+/HER2- Locally Advanced or Metastatic Breast Cancer

This Phase III, randomized, open label, multicenter study will evaluate the efficacy and safety of SIM0270 combined with everolimus compared to physician's choice of treatment in subjects with ER+/HER2- locally advanced or metastatic breast cancer who have had previous treatment with CDK4/6 inhibitor.

开始日期2024-11-14

申办/合作机构

江苏先声药业有限公司

[+1]

NCT06654791

/ Active, not recruiting临床1期

A Phase I Clinical Study to Evaluate the Mass Balance of [14C]SIM0270 in Healthy Chinese Adult Subjects

This is a single-center, non-randomized, open-label, single-cohort, single-dose phase I clinical study in healthy Chinese adult male subjects.

开始日期2024-10-17

申办/合作机构

江苏先声药业有限公司

[+1]

NCT06536036

/ Completed临床1期

A Single Center, Randomized, Open Label, Single Dose, Two-Period, Crossover Phase I Study to Evaluate the Effect of Food (high-fat/standard Meal) on the Pharmacokinetics of SIM0270 in Healthy Adult Subjects in China

This is a randomized, open label, single dose, two-period, crossover trial phase I study.
The purpose of this study is to evaluate the food effect on the pharmacokinetics（PK） of SIM0270 after oral administration under fasted, standard meal, or high-fat diet conditions.

开始日期2024-07-23

申办/合作机构

江苏先声药业有限公司

100 项与 SIM0270 相关的临床结果

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100 项与 SIM0270 相关的转化医学

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100 项与 SIM0270 相关的专利（医药）

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项与 SIM0270 相关的文献（医药）

2025-08-01·DRUG METABOLISM AND DISPOSITION

The application of mechanistic absorption, distribution, metabolism and excretion studies and physiologically-based pharmacokinetic modeling in the discovery of the next-generation oral selective estrogen receptor degrader camizestrant to achieve an acceptable human pharmacokinetic profile

Article

作者: Klinowska, Teresa ; Sykes, Andy ; Sharma, Pradeep ; Pop-Damkov, Petar ; Gangl, Eric T ; Scott, James S ; Sarkar, Ujjal ; Fretland, Adrian J ; Andersson, Linda ; Markandu, Roshini ; McGinnity, Dermot F ; Morentin-Gutierrez, Pablo

Camizestrant (AZD9833) is a potent, next-generation oral selective estrogen receptor (ERα) degrader (SERD) and complete ERα antagonist. It is currently being investigated in multiple phase 3 clinical trials for the treatment of ER+/HER2-negative breast cancer. ER is a clinically validated target, and when camizestrant was progressed into the clinic, the only approved SERD was fulvestrant which is delivered via once-monthly intramuscular injections. Oral delivery of a SERD has proved challenging, often due to poor pharmacokinetic (PK) properties and/or short half-life (t_1/2). Camizestrant is designed to overcome these challenges as a low molecular weight, low lipophilicity base with good permeability characteristics. It has extensive tissue distribution (Vdss 4-19 L/kg) and high bioavailability in animals, yet dose-dependent bioavailability (from 2 to >90%) in dogs. The in vitro hepatic metabolic intrinsic clearance (CL_int) for camizestrant varied across species with CL_int determined in human hepatocytes (530 μL/min/g liver) lower than rat (5900 μL/min/g liver) and dog (5000 μL/min/g liver). The K_m determined in dog liver microsomes (0.3 μM) was lower compared to humans (1 μM) and rats (6 μM). Cytochrome P450 phenotyping studies determined metabolism in dogs is primarily mediated by CYP2D15 whereas CYP3A4/5 are the dominant cytochrome P450 isoforms in humans. A physiologically-based pharmacokinetic model was developed and validated based on the integrated mechanistic data which recapitulated the observed dose-dependent exposure in dogs. Human exposures were simulated based on this model which incorporated human-specific parameters and indicated that human clearance was independent of dose at pharmacologically relevant concentrations. The simulated human PK parameters and exposure profile(s) were appropriate for the progression of camizestrant into phase 1 clinical evaluation. Clinical exposure data confirmed the preclinical predictions and have enabled rapid exploration of ERα pharmacology in patients. SIGNIFICANCE STATEMENT: This study demonstrates that understanding interspecies in vitro and in vivo pharmacokinetic properties is imperative to making human-specific PK predictions for candidate drugs. For camizestrant, physiologically-based pharmacokinetic simulations hypothesized concentration-dependent metabolism as the underlying cause for nonlinear PK in the dog. The analysis predicted broadly linear PK in humans at pharmacologically relevant doses. Despite uncertainty raised by the data in dogs, confidence in the predicted human PK profile, using human-relevant data, led to the progression of camizestrant to the clinical.

2025-06-24·Clinical Pharmacology in Drug Development

Disposition and Absolute Bioavailability of Oral Imlunestrant in Healthy Women: A Phase 1, Open-Label Study.

Article

作者: Hall, Stephen ; Cassidy, Kenneth ; Datta-Mannan, Amita ; Czeskis, Boris ; Shanks, Elaine ; Rodriguez Cruz, Vivian ; Yuen, Eunice

Imlunestrant (LY3484356) is a next-generation orally bioavailable selective estrogen receptor degrader being investigated for the treatment of estrogen receptor-positive advanced breast and endometrial cancers. This Phase 1, open-label, 2-part study evaluated the disposition and absolute bioavailability of [¹⁴C]-imlunestrant in 16 US-based healthy women (aged 36-65 years) of non-childbearing potential. Part 1 participants (N = 8) received an oral dose of 400-mg [¹⁴C]-imlunestrant solution (100 µCi). Part 2 participants (N = 8) received an oral dose of 2 × 200-mg imlunestrant tablets followed by approximately 45 µg [¹⁴C]-imlunestrant (approximately 1 µCi) given as a 15-minutes infusion 4 hour later. Blood, fecal, and urine samples were collected. Total radioactivity was primarily eliminated in feces (97.3%) with trace amounts recovered in urine (0.278%), suggesting minimal renal clearance. Imlunestrant accounted for most of the radioactive dose in feces (61.8%), followed by metabolite M2 (20.9%), metabolites M5 + M10 (coeluted), M7, M8, M9, and M11 (5.1% or less for each). Absolute bioavailability of imlunestrant after oral administration relative to intravenous administration was 10.9% based on dose-normalized area under the concentration-time curve from time zero to infinite time. Imlunestrant was well tolerated as an oral solution or as a tablet/intravenous dose. Eight participants reported mild/moderate treatment-related adverse events that resolved by the end of the study.

2025-06-12·JOURNAL OF MEDICINAL CHEMISTRY

Discovery and Characterization of PVTX-321 as a Potent and Orally Bioavailable Estrogen Receptor Degrader for ER+/HER2– Breast Cancer

Article

作者: Russell, Mike ; Chen, Zhixiang ; Lowenstein, Cassandra ; Havens, Courtney G. ; Strickland, Corey ; Rej, Rohan Kalyan ; Nagilla, Rakesh ; Deng, Qiaolin ; Wu, Wenxue ; Behshad, Elham ; Vidal, Brian ; Sui, Zhihua ; Zhang, Weihong ; Acharyya, Ranjan Kumar ; Zhang, Xuqing ; Kirchhoff, Paul ; Samanta, Debangshu ; Rice, Cory T. ; Wang, Shaomeng ; Xu, Guozhang ; Wu, Dimin ; Priestley, E. Scott ; Orth, Peter ; Jolivette, Larry ; Mohammad, Helai P.

Estrogen receptor α (ERα) is a key therapeutic target in ER+/HER2- breast cancer, but ESR1 mutations drive resistance to endocrine therapies. Heterobifunctional degraders (HBDs) targeting ERα offer a promising strategy to overcome this resistance. Here, we report PVTX-321 (16a), a potent ER HBD derived from a novel spirocyclic cereblon ligand and an ERα binder. PVTX-321 achieves a DC₅₀ of 0.15 nM in MCF-7 cells and acts as a strong antagonist (IC₅₀ = 59 nM), suppressing proliferation in ERα+ cell lines, including mutant variants (Y537S, D538G). It demonstrates favorable oral bioavailability, dose-dependent ERα degradation in vivo and induces tumor regression at 10 mg/kg (QD) in MCF-7 xenografts. With minimal CYP inhibition and a strong preclinical safety profile, PVTX-321 is a promising candidate for advancing ER+/HER2- breast cancer treatment.

项与 SIM0270 相关的新闻（医药）

2025-07-25

·医药观澜

乳腺癌治疗新曙光：靶向蛋白降解迎突破，多类疗法并进，为患者点燃新希望

编者按：2025年上半年，乳腺癌领域各类研发管线迎来重要进展，尤其是靶向蛋白降解（TPD）领域的突破引起行业高度关注。乳腺癌发病率高居所有女性恶性肿瘤首位。尽管诊疗水平不断提升，但该领域仍然面临诸多未竟需求，促使科学界探索更优的治疗方案。作为全球医药及生命科学行业创新的赋能者，药明康德也将持续通过一体化、端到端的CRDMO平台，为全球合作伙伴提供赋能，助力包括乳腺癌在内各类疾病的新药开发，为患者带来更多突破性的治疗方案。乳腺癌是全球女性健康面临的重大威胁。根据美国癌症协会《2024年癌症统计报告》（Cancer statistics，2024），乳腺癌已占据女性新发癌症病例的32%，高居所有女性恶性肿瘤首位。该协会还预测2025年仅在美国就将有约4.2万女性死于乳腺癌，这一严峻现实凸显了开发更有效治疗策略的紧迫性。当前，乳腺癌患者已有丰富的治疗选择，包括手术、放化疗、内分泌治疗、靶向治疗等，然而临床治疗仍面临诸多挑战，比如耐药性、副作用，以及某些特定亚型的乳腺癌（例如三阴性乳腺癌）患者依然缺乏针对性药物等等。这些治疗挑战促使研究领域持续探索更多更优的治疗策略。通过公开资料梳理，除了已获批上市的新药，当下还有数百款新药在临床研究阶段探索治疗乳腺癌的潜力，涵盖小分子和抗体，ADC等各类偶联药物、核酸和多肽药物，以及溶瘤病毒药物等等。剑指耐药性，靶向蛋白降解迎新突破，明星PROTAC分子申请上市小分子靶向疗法在过去十余年间取得重要突破，数十款小分子靶向新药已经获批治疗乳腺癌。当下，还有大量小分子新药在研，包含EGFR、PI3K/AKT/mTOR（PAM）等癌症信号通路抑制剂，以及基于表观遗传、细胞凋亡、合成致死等机制的新药。在小分子靶向治疗方面，耐药性的发生是一大挑战。导致乳腺癌靶向治疗耐药的一大原因是部分传统抑制剂仅能阻断蛋白功能而无法彻底清除致病蛋白。面对这一治疗瓶颈，靶向蛋白降解（TPD）技术展现出独特优势，近年来在包括乳腺癌在内的多种疾病治疗领域均受到广泛关注。这类小分子通过利用细胞的天然蛋白质降解机制特异性降解致病蛋白，不仅能克服传统激酶抑制剂的耐药性问题，更可靶向以往“不可成药”靶点，从而推动乳腺癌治疗模式从“功能抑制”到“蛋白清除”的转变。今年6月，由Arvinas和辉瑞（Pfizer）联合开发的PROTAC新药vepdegestrant已经向美国FDA递交上市申请，用于治疗既往接受过内分泌治疗的雌激素受体阳性（ER+）/人表皮生长因子受体2阴性（HER2-）、ESR1突变的晚期或转移性乳腺癌患者。这意味着靶向蛋白降解剂领域有望在近期迎来重要里程碑，也代表着乳腺癌治疗领域的新突破。Vepdegestrant是一款PROTAC雌激素受体降解剂，已经获得FDA授予的突破性疗法认定。若获批，该药将成为首个获美国FDA批准的PROTAC雌激素受体降解剂。通过公开渠道梳理，当下全球范围内还有数十款靶向蛋白降解剂正在临床阶段探索治疗乳腺癌的潜力，在乳腺癌新药管线中占据重要部分。这些蛋白降解剂包括了雌激素受体降解剂（SERD）、PROTAC、分子胶等类型，靶点涵盖ER、BRD4、CDK2、CDK4/6等乳腺癌领域的经典靶点。TPD技术在包括乳腺癌在内多个治疗领域的快速突破，离不开全球医药产业生态圈的共同努力。以PROTAC为例，这类分子复杂的化学结构显著增加了合成工艺开发的难度，其分子量大导致溶解性差、口服生物利用度低，成为阻碍它们迈向临床开发的重要因素。早在近十年前这项技术刚起步时，药明康德便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PROTAC分子的开发，其中20余款顺利推进至临床阶段。作为赋能全球靶向蛋白降解药物开发的重要平台之一，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性蛋白降解剂类型。例如，诱导细胞外或细胞膜蛋白进入溶酶体进行降解的溶酶体靶向嵌合体（LYTAC），将抗体与蛋白降解剂偶联产生的蛋白降解剂-抗体偶联药物（DAC），诱导靶蛋白被自噬体吞噬降解的自噬靶向嵌合小分子（AUTAC），以及靶向降解特定RNA的核糖核酸酶靶向嵌合体（RIBOTAC）等。上半年，还有多款基于TPD技术的创新疗法在乳腺癌治疗领域取得重要突破。例如：阿斯利康（AstraZeneca）公布了其下一代口服SERD药物camizestrant与CDK4/6抑制剂联用一线治疗HR+/HER2-晚期乳腺癌患者的3期临床数据，联合疗法将疾病进展或死亡风险降低56%。罗氏（Roche）在研的口服SERD药物giredestrant联合免疫治疗及CDK4/6抑制剂的1/2期临床试验结果显示，三联疗法治疗ER+/HER2-局部晚期或转移性乳腺癌患者表现出良好耐受性，且在ESR1突变型乳腺癌患者中优势更显著。先声药业在研的新型可透脑SERD分子SIM0270联合CDK4/6抑制剂在ER+/HER2-晚期乳腺癌患者中开展的1期研究结果显示，确认的客观缓解率（ORR）和临床获益率（CBR）分别为41.5%和82.5%，基线存在ESR1突变的患者ORR和CBR分别为87.5%和100%。百时美施贵宝在研的BMS-986449完成了1/2期临床研究患者招募，针对适应症涵盖三阴性乳腺癌。这是一款Cereblon E3连接酶调节药物（CELMoD）类分子胶降解剂，能够选择性降解调节性T细胞（Tregs）中的关键转录因子Helios（IKZF2）和Eos（IKZF4），通过重塑Tregs为效应型细胞，增强机体的抗肿瘤免疫应答。这些进展正在共同推动着靶向蛋白降解疗法在乳腺癌治疗中的应用边界不断拓展。图片来源：123RF多种疗法类型齐头并进，展现治疗潜力除了TPD之外，今年上半年还有多种类型的新药在乳腺癌治疗领域取得了多项重要进展，涉及抗体、ADC以及癌症疫苗等。比如在ADC领域，阿斯利康与第一三共开发的靶向Trop2的ADC药物Datroway（datopotamab deruxtecan）于年初获得FDA批准，用于治疗HR阳性、HER2阴性的成年乳腺癌患者，3期试验显示其可降低37%的疾病进展或死亡风险。同样由这两家公司联合开发的HER2靶向ADC药物Enhertu（trastuzumab deruxtecan）也于1月获FDA批准用于HR阳性、HER2低表达及超低表达乳腺癌，同时一项3期临床试验证明，该产品联合帕妥珠单抗一线治疗HER2阳性转移性乳腺癌可显著延长无进展生存期（PFS）超过3年。吉利德科学公司（Gilead Sciences）的Trop-2靶向ADC药物Trodelvy（sacituzumab govitecan）在3期试验中显示，对不适合接受PD-1/PD-L1抑制剂治疗的转移性三阴性乳腺癌（mTNBC）患者的一线治疗PFS优于标准化疗，有望成为首个适用于所有一线mTNBC患者的ADC药物。荣昌生物的HER2靶向ADC维迪西妥单抗在中国获批用于HER2阳性肝转移晚期乳腺癌，并在中国提交了针对HER2低表达乳腺癌适应症的上市申请。抗体领域也迎来新进展，比如今年5月，《柳叶刀-肿瘤学》（The Lancet Oncology）发表的一项研究结果显示，既往经治的HR+/HER2+转移性乳腺癌患者接受泽尼达妥单抗（百济神州和Zymeworks联合开发的一款HER2靶向双特异性抗体）联合哌柏西利和氟维司群的治疗，安全性可控且显示出具有前景的抗肿瘤活性，疾病控制率为91.3%。癌症疫苗疗法领域也迎来新进展，比如BriaCell Therapeutics在研的癌症疫苗Bria-IMT联合免疫检查点抑制剂的2期试验结果显示，该治疗方案在HR+转移性乳腺癌患者中的总生存期优于现有ADC药物。在三阴性乳腺癌患者中，Bria-IMT联合免疫检查点抑制剂治疗方案的生存数据则与一款ADC药物相当，但依然显著优于化疗治疗组，生存率提高约70%。Bria-IMT方案是一种基于异体全细胞的免疫疗法，可刺激患者的免疫系统诱导靶向杀死癌细胞。随着对乳腺癌生物学特性认知的不断深入以及药物研发的突破性进展，乳腺癌领域的治疗格局正在发生变化。在这场对抗乳腺癌的征程中，作为全球医药健康产业的积极贡献者，药明康德始终致力于通过一体化CRDMO模式，助力全球医药创新，为客户、为行业、为患者创造价值，助力合作伙伴加速更多好药新药问世。参考资料：[1] Wang, Zhenjie et al. “PROTAC: Novel degradable approach for different targets to treat breast cancer.” European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences vol. 198 (2024): 106793. doi:10.1016/j.ejps.2024.106793[2] Siegel RL, Giaquinto AN, Jemal A. Cancer statistics, 2024. CA Cancer J Clin. 2024; 74(1): 12-49. doi:10.3322/caac.21820[3] Jin, Yerim, and Yeongju Lee. “Proteolysis Targeting Chimeras (PROTACs) in Breast Cancer Therapy.” ChemMedChem vol. 19,23 (2024): e202400267. doi:10.1002/cmdc.202400267[4] Zhong, G., Chang, X., Xie, W. et al. Targeted protein degradation: advances in drug discovery and clinical practice. Sig Transduct Target Ther 9, 308 (2024). https://doi.org/10.1038/s41392-024-02004-x[5] Key Statistics for Breast Cancer. Retrieved July 7,2025.From https://www.cancer.org/cancer/types/breast-cancer/about/how-common-is-breast-cancer.html[6] Nolan, Emma et al. “Deciphering breast cancer: from biology to the clinic.” Cell vol. 186,8 (2023): 1708-1728. doi:10.1016/j.cell.2023.01.040[7] Leon-Ferre, Roberto A, and Matthew P Goetz. “Advances in systemic therapies for triple negative breast cancer.” BMJ (Clinical research ed.) vol. 381 e071674. 30 May. 2023, doi:10.1136/bmj-2022-071674[8] Matthias Hinterndorfer et al. Targeted protein degradation for cancer therapy. Nature Reviews Cancer（2025）版权说明：本文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。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。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。

抗体药物偶联物蛋白降解靶向嵌合体

2025-05-26

·先声药业

先声再明创新药18项研究将亮相2025年ASCO年会

全球临床肿瘤学盛会——2025年美国临床肿瘤学会（ASCO）年会将于5月30日至6月3日在美国芝加哥举行。先声再明苏维西塔单抗、SIM0270（新一代口服SERD分子）两款在研创新药，科赛拉®、恩维达®、恩度®三款已上市创新药共18项研究被大会收录，将向全球肿瘤科学界展示最新临床数据。先声再明产品相关研究入选摘要总数18篇，其中两项同时涉及2款产品（恩度®+恩维达®、恩维达®+科赛拉®）苏维西塔单抗：完成首个铂耐药卵巢癌人群OS获益显著的血管靶向药Ⅲ期临床试验在化疗基础上联合苏维西塔单抗显著改善了铂耐药卵巢癌患者的预后，且安全性可管理。试验组较对照组OS的延长具有统计学意义（HR 0.768， p=0.0304），死亡风险降低23%，中位OS为15.31 vs 14.03个月，2年生存率提高约50%（33.0% vs 22.3%），PFS、ORR及DCR等均明显改善。类型：壁报作者：中国医学科学院肿瘤医院吴令英教授等摘要号：5554（展板号452）SIM0270：新型口服SERD进入临床Ⅲ期该随机、开放标签 Ⅲ 期临床试验正在进行中，计划在中国约 50 个研究中心入组 460 名患者。主要终点为由盲法独立审查委员会 (BIRC) 评估的无进展生存期 (PFS)。次要终点包括由研究者评估的 PFS、总生存期 (OS)、客观缓解率 (ORR)、缓解持续时间 (DoR)、临床获益率 (CBR)、至疾病进展时间 (TTP)、安全性、药代动力学 (PK) 和患者报告结局 (PRO)。类型：壁报作者：复旦大学附属肿瘤医院吴炯教授等摘要号：TPS1128 （展板号：103a）SIM0270与哌柏西利联合使用，对晚期乳腺癌患者用表现出可接受的安全性和耐受性，对 ER+/HER2-晚期乳腺癌患者有良好的临床疗效。疗效可评估的患者中，确认的总缓解率 (ORR)为 41.5%，临床获益率(CBR) 为 82.5%。中位PFS 未达到 (NR)。在基线时存在 ESR1 突变的患者中，ORR 和 CBR 分别为 87.5% (7/8) 和 100% (8/8)。类型：壁报作者：复旦大学附属肿瘤医院吴炯教授等摘要号：1069 （展板号47）科赛拉®（注射用曲拉西利）探索多瘤种化疗骨髓保护类型：在线出版作者：复旦大学附属肿瘤医院王佳蕾教授等摘要号：e20562类型：在线出版作者：新乡医学院第一附属医院姬颖华教授等摘要号：e15109 类型：在线出版作者：Baylor大学医学中心Varada Salimath等摘要号：e20134类型：在线出版作者：印第安纳大学医学院Weston He等摘要号：e20116恩维达®（恩沃利单抗）生物标志物与联用方案不断丰富该研究的第一部分确定了tTMB ≥ 13 mut/Mb作为高肿瘤突变负荷的阈值。初步疗效结果显示，tTMB ≥ 13 mut/Mb患者的 ORR 和 DOR（33.3% 和 20.2 个月）高于 tTMB < 13 mut/Mb 患者（4.3% 和 3.8 个月）。TMB 可作为预测既往接受过治疗的晚期实体癌患者对恩沃利单抗疗效的生物标志物。类型：壁报作者：北京大学肿瘤医院李健教授等摘要号：2595（展板号：242）恩沃利单抗联合卡铂和依托泊苷对于 ES-SCLC 患者具有良好的临床疗效且安全性可控。31例患者中ORR为87.1%，DCR为100%（95% CI，88.8%-100%）。中位DoR为5.47个月，中位PFS为6.43个月，中位OS为20个月。类型：壁报作者：中国人民解放军总医院焦顺昌教授等摘要号：8090（展板号：211）类型：在线出版作者：河南省胸科医院李瑞杰教授等摘要号：e14610类型：在线出版作者：河南省人民医院魏立教授等摘要号：e20510类型：在线出版作者：安徽医科大学第一附属医院张梅教授等摘要号：e16385类型：在线出版作者：苏州大学附属第一医院李伟教授等摘要号：e16231类型：在线出版作者：上海市第六人民医院周陈亮教授等摘要号：e23506类型：在线出版作者：福建医科大学附属协和医院康明强教授等摘要号：e16115类型：在线出版作者：浙江大学邵逸夫医院陈鸣宇教授等摘要编号：e16289恩度®（重组人血管内皮抑制素）双恩联合减毒增效恩沃利单抗+恩度与化疗联合使用可获得良好的临床结果，且安全性可控。26例患者中ORR为65.4%，DCR为96.2%。中位PFS（mPFS）为12.4个月，1年PFS率为59.9%。中位总生存期 (mOS) 为 24.6 个月，1 年总生存率为 70.7%，2 年总生存率为 54.7%。33.3%的患者出现免疫相关 AE，未观察到新的AE。类型：壁报作者：山东大学齐鲁医院刘联教授等摘要号：8573（展板号：53）类型：在线出版作者：浙江省肿瘤医院陈晓钟教授等摘要号：e18016先声再明是先声药业集团旗下专注于抗肿瘤创新药研发、生产和商业化的生物医药公司，2023年起独立运营，致力于以突破性治疗手段, 解决中国乃至全球肿瘤领域巨大的未满足临床需求。再明着力打造高价值创新管线，已上市产品组合包含科赛拉®、恩维达®、恩度®、恩立妥®4款创新药。再明与全球合作伙伴的协同创新，为临床提供更有效的治疗手段，让更多肿瘤患者再现生机与光明。媒体联络：pr@zaiming.com编辑 | 李逸玲审校 | 周涛杨晨审核 | 耿猛唐任宏

临床结果ASCO会议临床3期

2025-04-23

·PipelineReview

Ensem Therapeutics Announces U.S. FDA IND Clearance to Initiate Clinical Development of ETX-636

– First-in-human trial of ETX–636 to begin in Q2 2025 in patients with tumors harboring an activating PI3K α mutation, including breast cancer – ETX-636 preclinical data to be presented at the AACR annual meeting, showcasing superior potency and selectivity for all mutant forms of PI3K α while sparing wildtype PI3Kα WALTHAM, MA, USA I April 22, 2023 I Ensem Therapeutics, Inc. (ENSEM) today announced the clearance of its Investigational New Drug (IND) application by the U.S. Food and Drug Administration (FDA) for ETX-636, a potential best-in-class novel allosteric pan-mutant-selective PI3Kα inhibitor and degrader, with its first-in-human study anticipated in the second quarter of 2025. In addition, ENSEM will present preclinical data on April 28 th at the American Association for Cancer Research (“AACR”) Annual Meeting in Chicago, Illinois, supporting a differentiated profile of ETX-636 and its potential to deliver clinical benefit to patients with tumors harboring activating PI3Kα mutations. Mutant PI3Kα is a key and frequent oncogenic driver across a broad spectrum of cancers, including up to 40 percent of hormone receptor-positive (HR+) /HER2-negative advanced breast cancers. However, wildtype PI3Kα is central to glucose homeostasis, and ATP-binding-site inhibitors target both mutant and wildtype PI3Kα, resulting in hyperglycemia which limits the clinical utility of these therapeutics. “Targeting mutant PI3Kα within tumors while sparing wildtype PI3Kα in normal tissues represents a significant clinical challenge, which ETX-636 overcomes. The IND clearance is an important milestone for the company, and we are laser-focused on driving ETX-636 through clinical development,” said Shengfang Jin, PhD, CEO and Co-Founder of ENSEM. Dr. Jin noted that ETX-636 is the second novel ENSEM compound entering clinical development. ETX-197, an oral selective CDK2 inhibitor licensed to BeOne and being developed as BG-68501, is currently undergoing Phase 1 clinical development in advanced or metastatic solid tumors associated with CDK2 dependency. Jeffery Kutok, MD, PhD, ENSEM’s Chief Scientific Officer, added, “ETX-636 is a potent pan mutant-specific allosteric PI3Kα inhibitor and degrader, which differentiates it from other compounds in its class. We are excited to evaluate ETX-636’s therapeutic potential in patients in our upcoming clinical trial. ENSEM also eagerly anticipates INDs for additional pipeline programs in 2026.” The initial first-in-human, Phase 1/2 study will evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of ETX-636 in participants with advanced solid tumors harboring a PI3Kα mutation. ETX-636 will be administered alone and in combination with fulvestrant, a selective estrogen receptor degrader approved for the treatment of advanced hormone receptor HR+/HER2- breast cancer. Poster Details About ETX-636 ETX-636 was designed to optimally fit into a specific allosteric binding site in p110α, the catalytic subunit of PI3Kα. This allosteric binding site has been shown to selectively inhibit multiple activating mutant forms of PI3Kα, including hotspot kinase and helical domain PI3Kα mutants, while sparing wildtype PI3Kα. The selectivity of ETX-636 for mutant PI3Kα greatly reduces the risk for hyperglycemia and other wildtype PI3Kα-related adverse events compared to non-mutant selective PI3Kα inhibitors. In addition to its potent inhibitory effect on mutant PI3Kα catalytic activity, ETX-636 also leads to proteasome-dependent degradation of mutant PI3Kα, while sparing wildtype protein (a feature not seen with other pan-mutant allosteric inhibitors). This dual mechanism of action results in deep and durable pathway inhibition and induces concordant tumor regression in kinase and helical domain PI3Kα-mutant breast cancer xenograft models as monotherapy and in combination with fulvestrant. In preclinical toxicology studies, blood glucose levels after dosing in multiple species indicate that ETX-636 did not disrupt glucose homeostasis at predicted human efficacious doses. About Ensem Therapeutics ENSEM is a pioneering drug discovery and development company that leverages its unique Kinetic Ensemble ® platform to advance innovative small molecule precision medicines for oncology. ENSEM integrates AI deep learning and advanced computational and cutting-edge experimental methodologies to identify non-obvious binding pockets and accelerate structure-based drug design, with a focus on high-value and difficult-to-drug targets. For more information, please visit www.ensemtx.com , or engage with us on LinkedIn . SOURCE: Ensem Therapeutics

临床申请临床1期AACR会议

100 项与 SIM0270 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
ER阳性/HER2阴性乳腺癌	临床3期	中国	南京再明医药有限公司	2024-11-14
ER阳性/HER2阴性乳腺癌	临床3期	中国	江苏先声药业有限公司	2024-11-14
局部晚期乳腺癌	临床3期	中国	江苏先声药业有限公司	2024-11-14
HEGF2阴性乳腺癌	临床1期	中国	江苏先声药业有限公司	2022-05-18

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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


NCT05293964 (Phase I study, ASCO2025)	临床1期	ER阳性/HER2阴性乳腺癌 ESR1 mutation	44	SIM0270 + Palbociclib	膚窪顧餘簾衊簾鹽餘鹹(鏇窪壓積窪鑰遞顧糧糧) = 壓艱獵製鬱遞廠糧觸積顧襯築鑰顧窪壓艱鏇鏇 (蓋憲範願範獵窪鹹獵廠 ) 更多	积极	2025-05-30
NCT05293964 (SABCS2024) 人工标引	临床1期	ER阳性/HER2阴性乳腺癌 HER2 Negative \| ER Positive	51	SIM0270 60mg	顧鹹鬱淵鹽簾鹽鏇製衊(簾遞蓋廠獵憲鹹鑰齋鏇) = 鹹鏇簾鑰鹽願蓋膚構繭鹹齋蓋選壓簾糧顧鹹餘 (遞夢蓋積窪齋廠夢顧窪 ) 更多	积极	2024-11-26
NEWS 人工标引	临床1期	ER阳性/HER2阴性乳腺癌 HER2 Negative \| ER Positive \| ESR1 Mutation	57	SIM0270	積積襯積選鹹壓艱蓋膚(齋齋網壓夢願遞襯襯醖) = 範獵簾餘鹹膚鹹憲餘網鹽願積廠醖鹹鏇夢積鑰 (壓壓築獵廠衊夢顧鑰鹹 ) 更多	积极	2023-12-12
NEWS 人工标引	临床1期	ER阳性/HER2阴性乳腺癌 HER2 Negative \| ER Positive \| ESR1 Mutation	57	SIM0270 (ESR1突变)	齋膚範繭憲製艱獵衊齋(構選鹽築憲鬱夢範繭選) = 範醖鹽膚艱糧憲憲糧築衊壓餘夢艱廠蓋簾顧窪 (顧膚遞積網壓鏇遞餘壓 )	积极	2023-12-12