一项评估Saruparib（AZD5305）联合Camizestrant(AZD9833)相比医生选择的CDK4/6抑制剂联合内分泌治疗或联合AZD9833用于BRCA1、BRCA2或PALB2突变的激素受体阳性、HER2阴性（IHC 0、1+、2+/ISH未扩增）晚期乳腺癌患者一线治疗的随机、开放性、III期研究（EvoPAR-Breast01）

1.主要目的：根据PFS评估结果，证明AZD5305+AZD9833相对于医生选择的CDK4/6i+ET的优效性。 2.关键次要目的：根据OS评估结果，证明AZD5305+AZD9833相对于医生选择的CDK4/6i+ET的优效性。

开始日期2025-01-21

申办/合作机构

AstraZeneca AB

[+1]

NCT06547164

/ Completed临床1期

A Phase I, Open-label, 2 Part, Fixed Sequence Study to Assess the Effect of Co-administration of Camizestrant (AZD9833) on the Pharmacokinetics of Midazolam Exposure (CYP3A4/5 Substrate) and of Carbamazepine (CYP3A4/5 Inducer) on Camizestrant Exposure in Healthy Post Menopausal Female Participants

This study will be conducted in order to determine the effect of repeated oral doses of camizestrant on the pharmacokinetics (PK) of midazolam and to determine the effect of repeated oral titrated doses of carbamazepine on the PK of camizestrant in healthy post-menopausal female participants.

开始日期2024-08-27

申办/合作机构

AstraZeneca PLC

NCT06380751

/ Recruiting临床3期

A Randomised, Open-Label, Phase III Study of Saruparib (AZD5305) Plus Camizestrant Compared With Physician's Choice CDK4/6 Inhibitor Plus Endocrine Therapy or Plus Camizestrant for the First-Line Treatment of Patients With BRCA1, BRCA2, or PALB2 Mutations and Hormone Receptor Positive, HER2-Negative (IHC 0, 1+, 2+/ ISH Non-amplified) Advanced Breast Cancer (EvoPAR-Breast01)

The primary objective of the study is to measure efficacy of saruparib (AZD5305) plus camizestrant compared with physician's choice CDK4/6i plus ET in patients with BRCA1, BRCA2, or PALB2m, HR-positive, HER2-negative (defined as IHC 0, 1+, 2+/ ISH non-amplified) advanced breast cancer

开始日期2024-08-01

申办/合作机构

AstraZeneca PLC

100 项与 Camizestrant 相关的临床结果

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100 项与 Camizestrant 相关的转化医学

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100 项与 Camizestrant 相关的专利（医药）

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项与 Camizestrant 相关的文献（医药）

2025-08-11·CLINICAL CANCER RESEARCH

Camizestrant in combination with three globally approved CDK4/6 inhibitors in women with ER+, HER2- advanced breast cancer: Results from SERENA-1.

Article

作者: Ciruelos, Eva ; Mathewson, Alastair M ; Armstrong, Anne ; Ciardullo, Carmela ; Sykes, Andy ; Kabos, Peter ; Hamilton, Erika ; Victoria, Ivan ; Klinowska, Teresa ; Baird, Richard D ; Ruiz-Borrego, Manuel ; Oliveira, Mafalda ; Morrow, Christopher J ; Vaklavas, Christos ; Patel, Manish R ; Twelves, Chris J ; Yang, Jincheng ; Turner, Nicholas ; Moreno, Irene ; Zhang, Bairu ; Lindemann, Justin P O ; Bermejo de Las Heras, Begoña ; Incorvati, Jason

PURPOSE:

This trial investigated safety and tolerability of camizestrant with CDK4/6 inhibitors (CDK4/6i), in women with ER+, HER2- advanced breast cancer.

PATIENTS AND METHODS:

SERENA-1 (NCT03616587) is a Phase 1, multi-part, open-label study in women with refractory ER+, HER2- advanced breast cancer. Patients received oral once-daily camizestrant 75 or 150 mg plus abemaciclib; camizestrant 75, 150, or 300 mg plus palbociclib; or camizestrant 75 mg plus ribociclib 400 or 600 mg. Safety/ tolerability, pharmacokinetics, efficacy, and impact on ESR1m ctDNA was assessed.

RESULTS:

By September 16, 2024 (data cut-off), 53 patients had received camizestrant plus abemaciclib, 78 plus palbociclib, and 60 plus ribociclib. Patients had a median of 2 (range 0-7) prior regimens for advanced disease; 83% had received a prior CDK4/6i and 59% prior fulvestrant. The most common TEAE for camizestrant 75 mg (Phase 3 dose) plus each CDK4/6i were diarrhoea (with abemaciclib [87.5%]), and neutropenia (with palbociclib [80%] and ribociclib [32.1% for 400 mg, 53.1% for 600 mg]). Median camizestrant tmax was ~4 hours post dose across combinations, with an estimated half-life of 9.5-17 hours. No clinically meaningful drug-drug interactions. were evident. In this heavily pre-treated population, CBR24 was 49.5% and median PFS was 7.4 months (95% CI: 5.3-9.3), with anti-tumor activity across all combinations, including patients previously treated with CDK4/6i and/or fulvestrant, with or without ESR1m.

CONCLUSION:

Camizestrant is well-tolerated, with anti-tumor activity in combination with CDK46i. These results support evaluation of camizestrant 75 mg plus standard CDK4/6i doses in Phase 3 trials.

2025-08-07·NEW ENGLAND JOURNAL OF MEDICINE

First-Line Camizestrant for Emerging ESR1 -Mutated Advanced Breast Cancer

Article

作者: Klinowska, Teresa ; Janni, Wolfgang ; Moreau, Lionel ; Huang-Bartlett, Cynthia ; McClain, Sasha ; Kalinsky, Kevin ; Pascual, Javier ; Fasching, Peter A. ; Jung, Kyung Hae ; Nowecki, Zbigniew ; Cristofanilli, Massimo ; Brufsky, Adam ; Bidard, François-Clément ; Gal-Yam, Einav Nili ; Chen, Shin-Cheh ; Pernas, Sonia ; Iwata, Hiroji ; Ma, Cynthia ; Turner, Nicholas C. ; Chia, Stephen ; He, Wei ; Bianchini, Giampaolo ; Mayer, Erica L. ; Karadurmus, Nuri ; Park, Yeon Hee

BACKGROUND:

Mutations in ESR1 are the most common mechanism of acquired resistance to treatment with an aromatase inhibitor plus a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor for advanced breast cancer. Camizestrant, a next-generation selective estrogen-receptor (ER) degrader and complete ER antagonist, has shown antitumor activity in ER-positive advanced breast cancer.

METHODS:

We tested patients with advanced breast cancer with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative tumors for ESR1 mutations in circulating tumor DNA (ctDNA) once every 2 to 3 months. All the patients had received at least 6 months of first-line therapy with an aromatase inhibitor plus a CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib). Patients who were found to have an ESR1 mutation and did not have radiologic progression were assigned in a 1:1 ratio to switch to camizestrant (75 mg once daily) with a continued CDK4/6 inhibitor plus placebo in place of an aromatase inhibitor or to continue to receive an aromatase inhibitor plus a CDK4/6 inhibitor plus placebo in place of camizestrant. The primary outcome was investigator-assessed progression-free survival.

RESULTS:

A total of 3256 patients were tested for an ESR1 mutation. The 315 eligible patients were assigned to switch to camizestrant (157 patients) or to continue to receive an aromatase inhibitor (158 patients). At an interim analysis at a median follow-up of 12.6 months, the median progression-free survival was 16.0 months (95% confidence interval [CI], 12.7 to 18.2) in the camizestrant group and 9.2 months (95% CI, 7.2 to 9.5) in the aromatase-inhibitor group (hazard ratio for progression or death, 0.44; 95% CI, 0.31 to 0.60; P<0.0001). The median time until a deterioration in the patient-reported global health status and quality of life occurred was 21.0 months with camizestrant and 6.4 months with an aromatase inhibitor (hazard ratio, 0.54; 95% CI, 0.34 to 0.84). The frequency of discontinuation because of adverse events was 1.3% with camizestrant and 1.9% with an aromatase inhibitor.

CONCLUSIONS:

In patients with ER-positive, HER2-negative advanced breast cancer with an ESR1 mutation that emerged during treatment, those who were switched to camizestrant with continuation of a CDK4/6 inhibitor during first-line therapy had significantly longer progression-free survival than those who maintained the aromatase-inhibitor combination. (Funded by AstraZeneca; SERENA-6 ClinicalTrials.gov number, NCT04964934.).

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.

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项与 Camizestrant 相关的新闻（医药）

2025-08-05

·Firstwordpharma

AstraZeneca taps SOPHiA GENETICS' AI to advance breast cancer research

SOPHiA GENETICS is deepening its long-standing alliance with AstraZeneca. Under the new collaboration, SOPHiA's multimodal AI Factories will be used to study the therapeutic efficacy, real-world performance and value of treatments for specific types of breast cancer. The multi-year initiative will also further support development of a tailored, AI-powered predictive model aimed at optimising outcomes for patients undergoing breast cancer treatment. "Our platform is purpose-built to manage complex healthcare data environments, and this collaboration reinforces our shared commitment to driving better patient outcomes through trusted, federated analytics powered by data and AI," Ross Muken, president of SOPHiA GENETICS, said in a release Tuesday. The company's AI Factories are proprietary analytical engines embedded in the SOPHiA DDM Platform that integrate and analyse multiple data types — including genomics, imaging and clinical data — to train predictive AI models for precision medicine. AstraZeneca will use the platform to uncover insights that could help improve treatment strategies for patients with breast cancer receiving its therapies. The partners will also work on gathering real-world evidence across Europe and North America to identify key drivers of treatment response, address knowledge gaps and support more informed clinical decision-making. "A core component of our AI strategy has been rooted in the deployment of frontier AI solutions across oncology clinical development," said Jorge Reis-Filho, chief AI and data scientist at AstraZeneca. "Fine tuning and augmenting our models with multimodal data — including our own data and the data that will be generated as part of this collaboration — is helping us to generate a more holistic understanding of disease biology and biomarkers to tailor the most effective treatment to patients living with cancer." AstraZeneca's breast cancer portfolio spans multiple subtypes. For HR+/HER2- breast cancer, approved treatments include oestrogen receptor antagonist Faslodex (fulvestrant) and PARP inhibitor Lynparza (olaparib), for patients with BRCA mutations. The company recently introduced capivasertib, an AKT inhibitor, and is developing camizestrant, an oral selective estrogen receptor degrader (SERD). In HER2+ and HER2-low disease, AstraZeneca co-develops the HER2-directed antibody-drug conjugate (ADC) Enhertu (trastuzumab deruxtecan) with Daiichi Sankyo. Another ADC, Datroway (datopotamab) deruxtecan, was recently approved for HR+/HER2- breast cancer following endocrine therapy. In triple-negative breast cancer, the PD-L1 inhibitor Imfinzi (durvalumab) is being studied in combination regimens. The partnership between SOPHiA and AstraZeneca began in 2023 to accelerate oncology drug development and support more targeted treatment strategies using SOPHiA's multimodal AI capabilities. The collaboration broadened in scope in late 2023 with the inclusion of Memorial Sloan Kettering Cancer Center, aiming to scale access to MSK's MSK‑ACCESS and MSK‑IMPACT genomic assays via the SOPHiA DDM cloud platform. AstraZeneca provided support to broaden deployment globally. During 2024, the partners rolled out MSK‑ACCESS powered by SOPHiA DDM across multiple institutions. By April 2025, the collaboration further expanded to reach 30 clinical institutions worldwide.

上市批准抗体药物偶联物

2025-07-31

·空之客

【医苑观畴】2025年二季度海外药企进展更新：阿斯利康AZN

1整体表现AZN在去年底中国区高管被查导致的股价急跌后，随着业绩极其刚健的成长，又迅速回稳到$220b左右，从大趋势上仍延续着“戴维斯双击”的范式。二季度核心业务收入同比增长11%、EPS同比增长12%，在MNC中处于靠前的水平；更令人赏心悦目的是，在肿瘤/心血管/呼吸/罕见病等板块、美/欧/中等市场的增长都非常均衡（即使是粗了大事的中国市场也保持着5%正增长）。全年指引基本维持不变，收入同比增长预计5-10%、EPS同比增长预计10-15%。2已上市产品分产品的增量来源将AZN的均衡性展露无遗，有5-10个产品都能贡献可观的增量，且都还没临近LOE，甚至后面还有一串“长尾”的增量品种（有趣的是“others”才是业绩增量的主要来源），这就能够对未来相当长时间的增长提供支撑。AZN可以说这几年是扛起了肿瘤一哥的大旗，肿瘤板块坐拥五个以上的重磅品种，而且近期都还在神奇地持续快速爬坡：Osimertinib在上市多年的情况下，在LAURA、FLAURA、ADAURA等系列试验支持下占住了EGFRm NSCLC各线的中坚地位，销售额仍在持续爬升，单季突破$1.8b、LTM累计已接近$6.9b，在这个卷疯了的适应症里展现出惊人的统治力；Durvalumab看似在PD-(L)1队伍中排不上号，但通过BTC/HCC/SCLC等差异化适应症，也不声不响爬到单季$1.5b、LTM累计$5.2b、增速保持在20%以上；Acalabrutinib与泽布替尼共同侵蚀着Ibrutinib的份额，特别是在1L CLL&MCL，LTM累计$3.3b，不过从上季度正式被泽布替尼反超后，差距大概率要被拉大；Olaparib仍旧是PARP抑制剂中的带头大哥，加上MRK的部分LTM累计达到$4.4b；备受关注的Enhertu，主要其实是靠DS带飞，特别是在HER2 Low乳腺癌和泛肿瘤等适应症在美国市场获批和中国市场纳入医保目录后，近几个季度持续爬坡，单季度稳稳站到$1b大关以上，总算有点对得起ADC一哥的咖位。心血管板块就靠大腿Dapagliflozin的炸裂表现带飞，在心衰和CKD两大适应症获批后，销售额爬升姿态完全不似已经上市超过10年的老药，单季冲破$2b大关后维持着10%增速一路上攻、LTM累计已接近$8.1b，在降糖领域已经有GLP-1这种毁天灭地大杀器存在的情况下依然十分耀眼。吸入制剂板块的Symbicort和Pulmicort等传统强势品种依然保持平稳，Breztri在LTM累计$1.1b。自免板块虽然没有那么闪耀的超重磅品种，但也都还算有看点，特别是TSLP单抗Tezepelumab上市两年来爬坡势头不错。在后新冠时代，传染病板块主要靠RSV，不过Nirsevimab上市后的体量还远不及预期，LTM累计$712m。收购Alexion得到的C5 franchise近期愈发不景气，gMG和PNH等重要适应症的竞争日趋激烈、再加上Part D的重拳，Ravulizumab增长明显遇到天花板，而Eculizumab在生物类似药上市后持续下滑，导致二者合计LTM累计销售额下滑到$6.3b，看起来跟当初$39b的收购对价渐行渐远；至于刚获批的TTR ASO产品Eplontersen，在ATTR-CM适应症之前估计销售额都还上不得台面。3在研管线近期AZN虽然没有前两年那样锋芒毕露，但依然以明确的思路和标准的动作向前推进，看每个季度的进展脑海中都能清晰浮现出其攻城略地的路径，只能用“稳如老狗”来形容。前两天还在感叹Roche从前“肿瘤一哥”的宝座滑落后的惨淡（参见【医苑观畴】2025年二季度海外药企进展更新：罗氏ROG），反观如今的AZN在肿瘤的布局堪称军容壮盛，既有势如破竹的尖兵，又有阵法严整的中军，还有力挽狂澜的奇兵。大杀器Enhertu在二线站稳脚跟后，终于在一线迎来历史性突破，在ASCO上公布的DESTINY-Breast09三期临床试验中，T-DXd联合Pertuzumab与标准治疗方案“妥妥组合”（Taxane+Herceptin+Perjeta，THP）对照，mPFS对比为40.7 vs 26.9个月（HR=0.56）、PFS2亦有优势（HR=0.6），ORR对比为85.1% vs 78.6%、mDOR也显著延长，OS尚不成熟、但已有改善趋势，这一结果将十多年前CLEOPATRA试验所定义的1L HER2+ BC金标准直接向上拔高了14个月的PFS，绝对具有里程碑意义。此外，另一项重要的三期临床DESTINY-Breast11试验也公布取得积极结果，针对早期患者的新辅助治疗，T-DXd联合THP与标准化疗方案联合THP，显著提高pCR，具体数据等ESMO。Osimertinib也终于在1L NSCLC上一锤定音，从去年公布了FLAURA2的惊艳PFS结果后，Osi联合化疗是否应该成为一线SOC尚存在少许争议，毕竟chemo-free还是拥趸颇多，终于完整OS分析也达到显著性，为Osi+chemo登顶一线标准疗法再加一波助力。Durvalumab也老夫聊发少年狂，在ASCO上公布的三期临床MATTERHORN试验结果中，针对围手术期的胃癌患者，Durvalumab联合标准化疗方案FLOT与单独FLOT相比，EFS改善非常显著（HR=0.71），pCR对比为19% vs 7%，OS虽未成熟但也获益趋势显著（HR=0.78）。此外，针对HR-NMIBC的三期临床POTOMAC试验也取得积极结果，Durvalumab联合标准疗法BCG与单独BCG相比DFS改善显著。口服SERD药物Camizestrant同样在ASCO上公布了三期临床SERENA-6试验中期分析的具体数据，针对一线ESR1m HR+/HER2- BC患者，Camizestrant联合CDK4/6抑制剂与AI+CDK4/6相比，mPFS为16.0 vs 9.2个月（HR=0.44），PFS2的HR=0.52，OS尚不成熟。这一结果不仅使得Camizestrant成为首个成功挤入一线的新一代口服SERD（sNDA已提交），而且更有意义的是在内分泌治疗作为HR+ BC治疗基石的情况下，一旦出现ESR1突变、即使未出现影像学进展，可立即从AI换药成SERD，有望改写整个领域的治疗范式。就算是一路走背字的Dato-DXd，也在经历了一系列溃败后终于守住了最后防线。从去年公布TROPION-Lung01试验OS不显著（参见【药海听涛】从PFS到OS的崩坏：看Dato-DXd肺癌三期数据变迁）并随后撤回2L non-sq NSCLC的BLA，重新提交的2L+ EGFRm NSCLC的BLA总算获得FDA的加速批准。这一批准的基础，是从整体并无OS获益的TL-01试验以及单臂的TL-05试验中刨出了117例EGFRm亚组结果，虽然说从non-sq退到EGFRm空间被大幅压缩了、且冲击1L难度增加，但好歹保住了获批这条底线，才更有底气地去搏AVANZAR这种试验，我愿将其视为堪称“中原皮旅”般的操作。心血管板块也出现重磅进展，当年以$1.8b收购Cincor得到的ALDOS抑制剂Baxdrostat，在三期临床BaxHTN试验中取得积极结果，在给药12周后，1/2mg两个剂量组相比安慰剂组都对收缩压有显著降低，且所有次要终点也都达到。在很多年都没有出现新机制药物的高血压领域，Baxdrostat无疑拥有了超重磅的潜力，甚至意味着AZN集齐了降糖（oGLP-1, SGLT-2）、降脂（oPCSK9, Lp(a)）、降压（ALDOS）等全套七龙珠。当年“冤大头”式收购Alexion得到的C5单抗Gefurulimab，总算也在上述前两代C5日渐式微的情况下，又让这笔收购巨款听了个响儿。在治疗AChR抗体阳性的gMG三期临床PREVAIL试验中，Gefurulimab达到所有主要和次要终点，其中26周时MG-ADL评分较基线得到显著改善。不过以当前gMG这种卷的程度（各路CAR-T、TCE、FcRn、APRIL/BAFF都在玩命招呼），C5到底能争下多少份额还有待观察。本季度最重要的BD交易，当属以$425m upfront + $575m milestone收购invivo CAR-T平台企业EsoBiotec，也打响了MNC争夺这一领域的第一枪。除此以外，还值得关注的进展包括：ICS/LABA/LAMA三联药物Breztri在KALOS和LOGOS两项治疗哮喘的三期临床中达到主要终点；而坏消息也是有的：轻链型淀粉样变性药物Anselamimab在三期临床CARES试验中未能达到主要终点，上一代C5单抗Eculizumab治疗狼疮肾炎的二期临床失败，另有靶向GPC3和Claudin18.2的CAR-T产品被移除出管线。在此还是要感叹AZN管线布局之严整，在不同疾病领域、以不同分子类型、处于不同确定性水平，长短结合、快慢有序，观之如戚家军鸳鸯阵，真的有那么一种孙子所云的“以正合、以奇胜”之感。番外重要中国资产交易作为全球肿瘤扛把子，AZN迟迟没有在PD1/VEGF上表态，自然也成为诸多中国公司盯着的潜在大买主。就在这个季度，公司首次将IO双抗单独作为一个策略写进了NSCLC的布局，然而目前这个策略的支柱是PD1/TIGIT和PD1/CTLA4，且分析师们拐弯抹角地试探对VEGF态度时，也得到了模棱两可的回答，你要说他们心里真的指望TIGIT和CTLA4这路货色能实现如此宏大的愿望，反正我我是不太信的。另一个备受瞩目的与中国企业合作的品种ECC-5004，已经有略长时间没有更新临床进展，甚至一度陷入了不利的传闻，这个季度终于悄然在附录里更新了糖胖二期临床SOLSTICE试验完成给药的信息。阿斯利康AZN往期季报分析：【医苑观畴】主流技术方向谁说了算：2022年上半年全球大药企核心产品管线进展总览【医苑观畴】主流技术方向谁说了算：2022年下半年全球大药企核心产品管线进展总览【医苑观畴】2023年上半年全球大药企核心进展总览【医苑观畴】2024年一季度海外药企进展更新：阿斯利康AZN【医苑观畴】2024年二季度海外药企进展更新：阿斯利康AZN【医苑观畴】2025年一季度海外药企进展更新：阿斯利康AZN

抗体药物偶联物

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

100 项与 Camizestrant 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
HR阳性/HER2阴性乳腺癌	申请上市	澳大利亚	AstraZeneca PLC	2025-05-05
晚期乳腺癌	临床3期	美国	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	中国	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	日本	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	阿根廷	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	澳大利亚	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	奥地利	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	巴西	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	保加利亚	AstraZeneca PLC	2024-08-01
晚期乳腺癌	临床3期	加拿大	AstraZeneca PLC	2024-08-01

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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


NCT04964934 (SERENA-6, Pubmed \| N Engl J Med)	临床3期	ER阳性/HER2阴性乳腺癌 \| HR阳性/HER2阴性乳腺癌一线	315	Camizestrant 75 mg once daily + CDK4/6 inhibitor + Placebo	廠餘網繭壓築夢艱鏇醖(觸築鏇遞範淵製範鹹窪) = 膚積夢鬱襯鑰繭蓋蓋糧選醖繭鏇夢觸鹹繭製蓋 (壓簾糧餘淵選膚鑰艱餘, 12.7 ~ 18.2)	积极	2025-08-07
				Aromatase inhibitor + CDK4/6 inhibitor + Placebo	廠餘網繭壓築夢艱鏇醖(觸築鏇遞範淵製範鹹窪) = 夢顧繭餘蓋壓壓網製蓋選醖繭鏇夢觸鹹繭製蓋 (壓簾糧餘淵選膚鑰艱餘, 7.2 ~ 9.5)
NCT04964934 (SERENA-6, BusinessWire) 人工标引	临床3期	ER阳性/HER2阴性/ESR1突变乳腺癌一线 HR Positive \| HER2 Negative \| ESR1 Mutation	315	Camizestrant + CDK4/6i	繭繭壓簾夢網蓋製膚鏇(壓觸糧構醖願網憲鏇願) = a highly statistically significant and clinically meaningful improvement in the primary endpoint of progression-free survival (PFS). 憲壓鑰築齋築鹽窪構選 (蓋餘鹹廠網鏇鑰遞遞築 ) 更多	积极	2025-02-26
NCT04588298 (SERENA-3, CTgov)	临床2期	ER阳性/HER2阴性乳腺癌 \| HER2 阴性乳腺癌	135	AZD9833 (AZD9833 75 mg (Stage 1 + 2))	壓夢憲鑰簾夢糧醖淵築(餘鏇襯壓簾襯積鹹選齋) = 遞製選窪簾膚壓鏇鹹糧夢壓鬱餘範範觸鏇鏇鬱 (窪選鏇夢獵襯艱網構鑰, 窪憲鹽餘築鹹築觸齋選 ~ 鹹夢範醖遞願窪餘醖網) 更多	-	2025-01-24
				AZD9833 (AZD9833 150 mg (Stage 1 + 2))	壓夢憲鑰簾夢糧醖淵築(餘鏇襯壓簾襯積鹹選齋) = 積遞衊獵窪夢顧獵艱餘夢壓鬱餘範範觸鏇鏇鬱 (窪選鏇夢獵襯艱網構鑰, 網構繭製衊艱構糧襯鹽 ~ 衊廠糧鬱壓遞築網襯鹹) 更多
NCT04214288 (SERENA-2, Literature) 人工标引	临床2期	ER阳性/HER2阴性乳腺癌 HER2 Negative	240	camizestrant 75 mg	廠廠製積壓糧夢壓範範(鑰膚鏇齋淵選糧蓋鹹獵) = 築製夢淵壓築繭鏇鏇蓋鏇糧獵膚餘鬱觸襯繭觸 (齋餘顧蓋衊糧壓鏇築醖, 3.7–10.9) 更多	积极	2024-11-09
				camizestrant 150 mg	廠廠製積壓糧夢壓範範(鑰膚鏇齋淵選糧蓋鹹獵) = 獵繭壓齋鏇蓋廠獵鬱蓋鏇糧獵膚餘鬱觸襯繭觸 (齋餘顧蓋衊糧壓鏇築醖, 5.5–12.9) 更多
NCT04588298 (SERENA-3, ESMO2024)	临床2期	-	-	Camizestrant 75 mg	網蓋遞鹹夢襯廠獵鹽範(簾衊齋製醖鬱鹹構製網) = 構壓壓壓遞餘糧顧選範衊壓憲網觸蓋醖窪簾築 (膚鏇憲壓鏇構選窪範齋 ) 更多	积极	2024-09-16
				Camizestrant 150 mg	網蓋遞鹹夢襯廠獵鹽範(簾衊齋製醖鬱鹹構製網) = 願鹽窪築遞積廠遞範構衊壓憲網觸蓋醖窪簾築 (膚鏇憲壓鏇構選窪範齋 ) 更多
NCT03616587 (SERENA-1, Pubmed) 人工标引	临床1期	ER阳性/HER2阴性乳腺癌二线 ER Positive \| HER2 Negative	108	Camizestrant 25 mg	齋淵膚蓋選淵蓋繭鏇鹽(遞鑰膚餘醖鹹獵鑰範鏇) = 82.4% of which were grade 1 or 2. The most common TRAEs were visual effects (56%), (sinus) bradycardia (44%), fatigue (26%), and nausea (15%). There were no TRAEs grade 3 or higher, or treatment-related serious adverse events at doses ≤150 mg. 醖醖繭鬱鏇廠積願選憲 (齋淵鹹鏇遞製鏇淵糧壓 ) 更多	积极	2024-05-08
				Camizestrant 75 mg
NCT04214288 (SERENA-2, CTgov)	临床2期	ER阳性/HER2阴性乳腺癌	240	fulvestrant	製壓襯觸觸構鹽構齋構(鏇願範範構鬱膚觸醖憲) = 製範繭衊蓋築糧簾鏇蓋繭獵淵齋觸鏇觸繭願憲 (夢繭鏇製廠觸醖齋構齋, 積鬱製鹽鹹選鏇築壓壓 ~ 選醖餘製繭選鹹鹹鹽簾) 更多	-	2023-12-12
NCT04711252 \| NCT03616587 \| NCT04964934 (SERENA-4, SERENA-6, SERENA-1, SABCS2023)	N/A	辅助 ESR1wt \| ESR1m \| Y537S mutation	-	Camizestrant (AZD9833) 75 mg	鑰願構齋醖醖夢構鏇餘(鹽憲鹹衊製鹽糧廠膚餘) = 餘觸淵壓鏇選淵鑰艱醖壓遞壓襯顧遞範窪艱廠 (夢選觸範鑰襯鹽襯夢夢 )	-	2023-03-01
				Placebo	鑰願構齋醖醖夢構鏇餘(鹽憲鹹衊製鹽糧廠膚餘) = 窪遞窪獵繭獵獵願獵襯壓遞壓襯顧遞範窪艱廠 (夢選觸範鑰襯鹽襯夢夢 )
NCT03616587 (SERENA-1, SABCS2023)	临床1期	ER阳性/HER2阴性乳腺癌 ESR1 mutations	24	Camizestrant 75 mg QD + Abemaciclib 150 mg BID	選鹹窪衊齋壓遞選糧蓋(願築網願齋夢廠鬱遞觸) = 繭廠齋選鬱築醖簾糧餘廠願觸觸醖製艱顧獵網 (鬱繭襯壓獵鏇憲範壓獵 ) 更多	积极	2023-03-01
NCT03616587 (SERENA-1, ASCO2022) 人工标引	临床1期	ER阳性/HER2阴性乳腺癌 ER Positive \| HER2 Negative	25	palbociclib+AZD9833	鬱膚襯鏇鑰觸顧鑰繭鹽(繭鏇積築夢衊鑰繭網醖) = 艱獵齋簾積衊襯範壓鑰蓋顧夢壓遞簾積襯憲鹽 (願鹽壓膚鹹艱鏇憲淵製 ) 更多	积极	2022-06-02