预约演示

更新于：2025-07-15

Rucaparib Camsylate

芦卡帕利

更新于：2025-07-15

概要

基本信息

药物类型

小分子化药

别名

Rubraca、rucaparib、Rucaparib phosphate

+ [11]

靶点

PARP1 x PARP2 x PARP3

作用方式

抑制剂

作用机制

PARP1抑制剂(聚腺苷二磷酸核糖聚合酶1抑制剂)、PARP2抑制剂(聚腺苷二磷酸核糖聚合酶2抑制剂)、PARP3抑制剂(聚腺苷二磷酸核糖聚合酶3抑制剂)

治疗领域

肿瘤消化系统疾病内分泌与代谢疾病+ [3]

在研适应症

输卵管癌卵巢上皮癌原发性腹膜癌+ [25]

非在研适应症

前列腺腺癌晚期乳腺癌晚期宫颈癌+ [23]

原研机构

Pfizer Inc.

在研机构

Pharma& Schweiz GmbH

Bristol Myers Squibb Co.

Clovis Oncology, Inc.

+ [5]

非在研机构

Hoffmann-La Roche, Inc.

Foundation Medicine, Inc.

Pfizer Inc.

+ [3]

权益机构

The University of Newcastle

TOLMAR, Inc.

Alkermes Plc

+ [5]

最高研发阶段批准上市

首次获批日期

美国 (2016-12-19),

BRCA 突变卵巢癌

最高研发阶段(中国)-

特殊审评突破性疗法 (美国)、加速批准 (美国)、孤儿药 (美国)

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结构/序列

分子式C29H34FN3O5S

InChIKeyINBJJAFXHQQSRW-STOWLHSFSA-N

CAS号1859053-21-6

关联

项与芦卡帕利相关的临床试验

CTRI/2022/11/047353

/ SuspendedN/A

A multicenter, randomized, open label, three treatment, three period, steady state, multiple dose, crossover, bioequivalence study of Rucaparib Tablets 300 mg manufactured by Watson Pharma Pvt. Ltd., India with RUBRACA (Rucaparib) Tablets 300 mg distributed by Clovis Oncology, Inc. under fasting condition in adult patients with epithelial ovarian or fallopian tube or primary peritoneal or metastatic castration-resistant prostate cancer and are receiving a regimen of Rucaparib.

开始日期2022-11-21

申办/合作机构

Watson Pharma Pvt Ltd.

CTRI/2022/02/040221

/ Recruiting临床2期IIT

177Lu-PSMA-617 plus low-dose rucaparib in metastatic castration-resistant prostate cancer: A randomized, controlled phase 2 trial (LuPlus) - LuPlus

开始日期2022-04-01

申办/合作机构-

NCT04455750

/ Active, not recruiting临床3期IIT

CASPAR - a Phase III Trial of Enzalutamide and Rucaparib As a Novel Therapy in First-Line Metastatic Castration-Resistant Prostate Cancer

This randomized, placebo-controlled phase III trial is evaluating the benefit of rucaparib and enzalutamide combination therapy versus enzalutamide alone for the treatment of men with prostate cancer that has spread to other places in the body (metastatic) and has become resistant to testosterone-deprivation therapy (castration-resistant). Enzalutamide helps fight prostate cancer by blocking the use of testosterone by the tumor cells for growth. Poly adenosine diphosphate (ADP)-ribose polymerase (PARP) inhibitors, such as rucaparib, fight prostate cancer by prevent tumor cells from repairing their DNA. Giving enzalutamide and rucaparib may make patients live longer or prevent their cancer from growing or spreading for a longer time, or both. It may also help doctors learn if a mutation in any of the homologous recombination DNA repair genes is helpful to decide which treatment is best for the patient.

开始日期2021-10-14

申办/合作机构

Alliance Foundation Trials LLC

[+1]

100 项与芦卡帕利相关的临床结果

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100 项与芦卡帕利相关的转化医学

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100 项与芦卡帕利相关的专利（医药）

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1,088

项与芦卡帕利相关的文献（医药）

2025-08-01·Asia-Pacific Journal of Clinical Oncology

BRCA Mutation Testing in Men With Metastatic Castration‐Resistant Prostate Cancer: Practical Guidance for Australian Clinical Practice

Review

作者: Goh, Jeffrey C. ; Azad, Arun A. ; Campbell, Ainsley ; Gurney, Howard ; Rathi, Vivek

Abstract:

Some patients with metastatic castration‐resistant prostate cancer (mCRPC) possess germline or acquired defects in the DNA damage repair (DDR) genes BRCA1 and BRCA2. Tumors with BRCA mutations exhibit sensitivity to poly‐ADP ribose polymerase inhibitors (PARPi) such as olaparib and rucaparib. As a result, molecular diagnostic testing to identify patients with BRCA mutations eligible for the PARPi therapy has become an integral component of managing patients with mCRPC. There are practical challenges in the current molecular testing pathway in Australia that can compromise testing success. Testing success is often contingent on quality of tissue handling and laboratory processing techniques to minimize DNA degradation and suboptimal sequencing data quality. Greater adoption of best testing practices in Australia can be facilitated with education and greater awareness of expert recommendations. Here, we provide expert recommendations on how to optimize BRCA molecular diagnostic testing in patients with mCRPC. Optimization and standardization of molecular diagnostic testing will support health care providers and institutes in establishing more efficient testing pathways, enabling access to targeted therapies such as PARPi, and improving patient outcomes.

2025-08-01·BIOORGANIC CHEMISTRY

Therapeutic approach for triple-negative breast Cancer through poly (ADP-ribose) Polymerase-1 inhibitors: Current update

Review

作者: Jaitak, Vikas ; Arya, Swati ; Das, Niranjan ; Bose, Sankhadip ; Kumar, Ashok ; Dwibedi, Vagish ; Panchpuri, Mitali ; Das, Agnidipta ; Gupta, Jeetendra Kumar ; Mandal, Sudip Kumar ; Abdel-Gawad, Hassan ; Samanta, Samir Kumar ; Rath, Santosh Kumar

Breast cancer is a dangerous disease that is common worldwide. It comprises 25 % of all women's cancers and 12 % of all new cancer cases diagnosed. Triple-negative breast cancer (TNBC) is a specific subtype of breast cancer that lacks the expression for three targetable biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2). TNBC accounts for 15-20 % of all breast cancers worldwide and is most prevalent in young African-American women, as well as premenopausal women. Unlike other types of breast cancer, TNBC has limited treatment options. Mutations in the Breast Cancer type 1 and type 2 genes (BRCA1/2) are associated with TNBC. However, researchers are investigating new approaches to treating this subtype. One promising area of research is focused on Poly (ADP-Ribose) Polymerases (PARPs), a family of enzymes involved in DNA repair. Inhibition of PARP-1 can led to the loss of DNA repair via BRCA-dependent mechanisms. PARP-1 inhibitors such as Olaparib, Rucaparib, Niraparib, and Talazoparib have shown promise in treating various types of cancer. These inhibitors are being tested both as monotherapy and in combination with other therapies, such as cytotoxic therapy or radiotherapy. This review article focuses on exploring the significance of PARP-1 inhibitors for TNBC. It delves into the mechanism of action and discusses current and future perspectives for using these inhibitors to treat TNBC.

2025-08-01·PATHOLOGY RESEARCH AND PRACTICE

Synergistic strategies: ADC-PARP inhibitor combinations in triple-negative breast cancer therapy

Review

作者: Rejili, Mokhtar

Triple-negative breast cancer (TNBC) continues to be a very aggressive subtype with few targeted therapy options. Antibody-drug conjugates (ADCs) and poly (ADP-ribose) polymerase inhibitors (PARPis) have been promising therapeutic strategies, each of which targets different vulnerabilities in TNBC cells. ADCs like sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) target cytotoxic payloads with specificity, whereas PARPis like olaparib, rucaparib, niraparib, and talazoparib cause synthetic lethality in homologous recombination repair (HRR)-deficient tumors. Recent clinical trials of SEASTAR and PETRA have evaluated ADC-PARPi combinations to enhance anti-tumor activity through DNA damage induction with the prevention of its repair. Early data demonstrate enhanced therapeutic outcomes, especially in BRCA-mutated and HRD-positive TNBC. Myelosuppression and adaptation of dosing regimens remain challenges to be addressed. Future directions include biomarker-driven patient selection, combination with immune checkpoint inhibitors, and advancement in next-generation ADCs. The synergistic potential of ADC-PARPi combinations provides a new avenue for overcoming TNBC resistance, enhancing treatment outcomes, and widening therapeutic strategies for this challenging disease.

170

项与芦卡帕利相关的新闻（医药）

2025-06-30

·EINPresswire

January - March 2025 | Potential Signals of Serious Risks/New Safety Information Identified by the FDA Adverse Event Reporting System (FAERS)

ELEVIDYS (delandistrogene moxeparvovec-rokl) Hepatotoxicity-associated fatalities in non-ambulatory patients with Duchenne muscular dystrophy FDA is evaluating the need for regulatory action. FDA Safety Communication was issued on June 24, 2025: FDA Investigating Deaths Due to Acute Liver Failure in Non-ambulatory Duchenne Muscular Dystrophy Patients Following ELEVIDYS Finasteride (compounded product) topical Adverse event FDA alerts health care providers, compounders and consumers of potential risks associated with compounded topical finasteride products Janus kinase (JAK) inhibitors Cerebral venous sinus thrombosis FDA is evaluating the need for regulatory action. Leqembi (lecanemab-irmb) injection Amyloid related imaging abnormality-edema/effusion FDA is evaluating the need for regulatory action. Ocaliva (obeticholic acid) tablets Liver disorder FDA is evaluating the need for regulatory action. Olanzapine-containing products Lybalvi (olanzapine and samidorphan) tablets Symbyax (olanzapine and fluoxetine) capsules Zyprexa (olanzapine) tablets Zyprexa Intramuscular (olanzapine) injection Zyprexa Relprevv (olanzapine) injectable suspension Zyprexa Zydis (olanzapine) tablets Inappropriate antidiuretic hormone secretion FDA is evaluating the need for regulatory action. Poly (ADP-ribose) polymerase (PARP) inhibitors Akeega (niraparib and abiraterone acetate) tablets Lynparza (olaparib) tablets Rubraca (rucaparib) tablets Talzenna (talazoparib) capsules Zejula (niraparib) tablets Vasculitis FDA is evaluating the need for regulatory action. Rilutek (riluzole) tablets Tiglutik (riluzole) oral suspension Pancreatitis acute FDA is evaluating the need for regulatory action. Suprep Bowel Pre Kit (sodium sulfate, potassium sulfate, and magnesium sulfate) oral solution Hypersensitivity FDA is evaluating the need for regulatory action. Vyvgart Hytrulo (efgartigimod alfa and hyaluronidase-qvfc) injection Severe worsening of chronic inflammatory demyelinating polyradiculoneuropathy FDA is evaluating the need for regulatory action. Xcopri (cenobamate tablets) Drug-induced liver injury FDA is evaluating the need for regulatory action. Legal Disclaimer: EIN Presswire provides this news content "as is" without warranty of any kind. We do not accept any responsibility or liability for the accuracy, content, images, videos, licenses, completeness, legality, or reliability of the information contained in this article. If you have any complaints or copyright issues related to this article, kindly contact the author above.

上市批准

2025-05-26

·echemi

8 to 0 Rejection FDA Halts Pfizer’s Prostate Cancer Combo Despite 9 Month Survival Boost

In a resounding 8-0 vote, the FDA’s Oncologic Drugs Advisory Committee (ODAC) rejected Pfizer’s combination of Talzenna and Xtandi for treating mCRPC patients without HRR mutations (non-HRRm). This decision deals a blow to one of Pfizer’s high-profile oncology strategies, despite notable improvements in survival outcomes reported in the TALAPRO-2 Phase III trial. According to final data, the combination extended radiographic progression-free survival (rPFS) to 33.1 months compared to 19.5 months in the control group. Overall survival (OS) improved by nearly 9 months, reducing the risk of death by over 20%. Among HRRm-positive patients, rPFS nearly doubled, and OS was prolonged by 14 months. However, the core issue lay with non-HRRm patients, where regulators questioned whether the observed OS improvement was statistically credible or the result of confounding variables. ODAC members raised concern that over a quarter of patients lacked confirmed HRR mutation status at randomization, and many of them were later found to be HRRm-positive. This undermined the reliability of the subgroup analysis. The FDA emphasized that biomarker-driven approvals must be rooted in prospective stratification, not retrospective data that might skew conclusions. While Pfizer argued the mechanistic rationale was strong—citing synergy between PARP inhibition and androgen receptor blockade—and manageable safety signals, including anemia and absence of MDS/AML, the advisory panel stood firm. Regulators warned this could set a dangerous precedent by encouraging biomarker-independent use of PARP inhibitors, a direction unsupported by past trials with olaparib and rucaparib in similar settings.

临床3期临床结果加速审批

2025-03-04

·ioncology

TBCR发表王树森教授综述，总结ADC治疗晚期TNBC研究进展

点击上方蓝字关注我们编者按：三阴性乳腺癌（TNBC）一直被认为是预后最差的乳腺癌类型，因为此类乳腺癌异质性强，缺乏明确有效的治疗靶点。尽管靶向、免疫治疗取得了一定的进展，但并未使晚期TNBC患者预后带来“质的飞跃”。抗体偶联药物（ADC）的更新迭代，为TNBC患者带来了新的治疗希望。近日，中山大学肿瘤防治中心王树森教授、蒋逵葵医生在《转化乳腺癌研究》（Translational Breast Cancer Research，TBCR）发表综述文章，总结了ADC治疗晚期TNBC的研究进展。《肿瘤瞭望》特邀王树森教授团队介绍该综述的亮点内容和精彩观点如下。原文链接： https://tbcr.amegroups.org/article/view/95768/html 要点精粹 · TNBC侵袭性强、预后差，仍以化疗为主，靶向、免疫治疗虽有突破，但并未尽如人意 · “魔法子弹”ADC理念历经百余年发展，经过数代的改良创新，新一代ADC在疗效和安全性方面均有显著提升 · 在晚期TNBC领域，SG、T-DXd等靶向Trop-2或HER2的ADC取得了突破性研究进展，并已改变临床实践，尤其SG成为国内外多个指南共识推荐的晚期TNBC二线治疗首选方案 · ADC在TNBC领域的应用将得到拓展，包括晚期一线治疗、早期新辅助和辅助治疗等，有望进一步改变临床实践中国乳腺癌患者中TNBC占比约为10.4%～13.5%，此类乳腺癌侵袭性强、转移风险高、患者预后差[1]，整体预后仍不如HR阳性和HER2阳性等其他乳腺癌亚型，是临床治疗的难点和研究的热点。目前，化疗仍是晚期TNBC的主要治疗选择，但毒副作用大，且疗效有限，≥2线治疗的晚期患者接受单药化疗的中位无进展生存期（PFS）小于3个月，客观缓解率（ORR）仅为11%[2]。近年来，免疫检查点抑制剂（ICI）和PARP抑制剂（PAPRi）等免疫、靶向治疗为晚期TNBC患者增加了新的治疗选择，但ICI主要在PD-L1阳性患者中有获益，且大多数接受ICI治疗患者都会出现获得性耐药，后续治疗仍然困难[3]；而PAPRi的相关研究虽然有PFS获益，但OS的改善没有达到统计学显著性[4-5]，且国内相关药物的临床使用尚未获批。由此可见，当前的研究进展或治疗药物仍难以满足晚期TNBC患者的临床需求。近年来，抗体偶联药物（ADC）在肿瘤治疗领域取得令人耳目一新的进展，ADC能否成为突破TNBC治疗困境的利刃，临床医生和患者对此充满期待。 TNBC领域ADC药物治疗的重要进展 ADC药物通常由三个部分构成：针对肿瘤靶抗原的单抗、高效的细胞毒性载荷以及连接二者的连接子；通过高选择性的药物递送，可降低小分子细胞毒性药物的脱靶毒副作用，有效提高抗肿瘤治疗的获益风险比[6]。根据ADC三个组成部分的迭代过程，ADC药物可以大致划分为3代：第一代ADC药物存在免疫原性高、药物异质性大等问题；第二代ADC通过改进抗体和连接子，降低免疫原性和提高药物稳定性，但仍有一定的药物异质性和脱靶毒性；第三代ADC的药物抗体比（DAR）和同质性得到优化，脱靶毒性更低，且旁观者效应对临近的抗原低表达肿瘤细胞也有杀伤能力。目前，已有多种针对不同靶点的ADC在晚期TNBC领域取得研究进展。 1 靶向Trop-2的ADC 人滋养层细胞表面抗原2（Trop-2）是一种跨膜糖蛋白，表达于多种恶性肿瘤细胞表面，作为肿瘤相关钙信号转导子影响预后和耐药性。Trop-2约在90% TNBC中呈中等或强阳性高表达[7]，被视为TNBC新型ADC药物的重要靶标。目前靶向Trop-2的ADC主要包括戈沙妥珠单抗（sacituzumab govitecan，SG）、Datopotamab deruxtecan（Dato-DXd）和SKB264。表1. TNBC领域靶向Trop-2的ADC结构简介 _ Trop-2单抗连接子载药 DAR SG 人源化IgG1 CL2A（pH敏感性） SN38（伊立替康衍生物） 7.6:1 Dato-DXd 人源化IgG1 GGFG四肽（酶敏感性） DXd（喜树碱衍生物） 4.0:1 SKB264 人源化IgG1 TL033（pH敏感性） T030（Belotecan衍生物） 7.4:1 SG SG由人源化IgG1和伊立替康衍生物SN38通过CL2A连接而成，DAR为7.6:1。SG具有对pH敏感的连接子，在肿瘤微环境或瘤细胞内的酸性环境中均可释放药载，并渗透进入邻近的Trop-2低表达癌细胞，发挥杀伤效应，从而构成双重“旁观者效应”。 III期ASCENT研究中，将SG或医生选择的化疗（TPC）用于治疗难治性或复发性晚期TNBC患者，这些患者接受过≥2线化疗（中位4线）且无脑转移，结果显示SG组的中位PFS是TPC组的三倍多，疾病进展或死亡风险降低61%（5.6 vs 1.7个月，HR 0.39）；而ORR则是TPC组的7倍（35% vs 5%），常见的≥3级治疗相关不良事件（TRAE）为中性粒细胞减少症等血液学毒性和腹泻，给予减药、暂停给药及对症处理后大部分患者可耐受[8-9]。EVER-132-001是一项多中心桥接试验，在80例曾接受≥2线标准化疗的中国晚期TNBC患者中验证了SG的疗效和安全性，并发现50%患者的瘤体尺寸缩小≥30%，且TRAE与UGT1A1基因型之间未发现关联[10]。值得注意的是，不同基线胚系BRCA1/2突变状态、Trop-2表达水平的患者均可从SG治疗中获益，即便Trop-2表达水平极低，SG的疗效仍显著优于化疗，这可能与SG具有双重旁观者效应相关，药载SN-38会因此进一步增强杀伤效应[11]。 Dato-DXd Dato-DXd由人源化IgG1和喜树碱衍生物DXd通过GGFG连接而成，DAR为4:1。I期TROPION-PanTumor01研究入组了44例接受过中位3线治疗的转移性TNBC患者，Dato-DXd治疗后ORR为32%，DCR为80%，中位PFS为4.3个月，中位OS为12.9个月，最常见≥3级TRAE是口腔炎、恶心、呕吐及乏力等[12]。 SKB264 SKB264由人源化IgG1和Belotecan衍生物T030通过TL033连接而成，DAR为7.4:1。一项II期队列扩展非随机研究（NCT04152499），纳入了59例经治的转移性TNBC患者，其中88%的患者接受过≥3线的治疗，SKB264治疗后ORR为40%，CBR为80%，≥3级TRAE发生率55.9%，最常见的是中性粒细胞减少、贫血和血小板减少，没有TRAE导致的死亡或间质性肺病[13]。 2 靶向HER2的ADC HER2通过多种信号途径调控细胞分裂和血管生成，在乳腺癌中，HER2阳性表达率为15%～25%[14]；大约有35%的TNBC存在HER2低表达（IHC 1+或IHC 2+/ISH阴性）[15]。乳腺癌的HER2表达具有异质性，表现为分子亚型、突变谱、HER2蛋白水平和免疫浸润等不同，并导致靶向HER2的ADC药物疗效不一[16]，而靶向Trop-2抗原的ADC药物不直接受HER2低表达或零表达水平的影响[11]，这对于乳腺癌具有重要意义。目前在TNBC中有较多研究的HER2 ADC为德曲妥珠单抗（Trastuzumab Deruxtecan, T-DXd），通过可酶切四肽接头将HER2单抗与DXd连接而成，DAR约为8。DESTINY-Breast04研究入组了557例既往接受过中位3线治疗的HER2低表达晚期乳腺癌患者，但HR阴性/HER2低表达患者仅58例，病例数有限且非预先指定分析的亚组，只能将该亚组患者的疗效列为探索性终点，最终观察到T-DXd治疗后PFS（8.5 vs 2.9个月）、OS（18.2 vs 8.3个月）和ORR（50% vs 16.7%）均较TPC对照组得到改善，16.2%的患者因TRAE而停药[17]。另一项II期DAISY研究则入组包括HER2过表达（72例）、HER2低表达（74例）和HER2零表达（40例）三个队列，HER2低表达或零表达队列（含TNBC）患者须为蒽环类和紫杉类药物经治，结果T-DXd治疗后HER2低表达和零表达队列的ORR分别达到37.5%和29.7%，中位PFS分别为6.7个月和4.2个月[18]。 3 靶向其他抗原的ADC 除Trop-2和HER2抗原外，目前还有HER3、B7-H4和LIV-1等其他抗原与ADC药物的研发相关，主要来自I/II期的早期研究探索。 _ U31402-A-J101[19] NCT05263479[20] NCT01969643[21] 药物 HER3-DXd HS-20089 Ladiratuzumab vedotin 靶抗原 HER3 B7-H4 LIV-1 临床研究分期 I/II期 I期 I期样本量 53例 16例 40例 ORR 22.6% 37.5% 28.0% 中位PFS 5.5个月 - - 中位OS 14.6个月 - - 常见TRAEs 胃肠道症状和血液毒性血液毒性，胃肠道症状，肝损伤胃肠道症状，疲劳，周围神经疾病 ADC对TNBC指南的影响及用药顺序在TNBC领域，SG和T-DXd是目前循证医学证据较为丰富的ADC，均已影响临床实践指南。SG的应用不受生物标志物的限制，基于多项有力的临床研究证据，CACA、CSCO、NCCN、ESMO等多个国内外指南一致推荐SG作为晚期TNBC二线治疗的优选[22-25]。T-DXd主要针对HER2低表达的晚期TNBC，NCCN、CSCO推荐其作为此类患者的二线治疗方案[23-24]；中国抗癌协会（CACA）乳腺癌诊治指南与规范（2024年版精要本）在转移性乳腺癌区分和治疗策略中指出，HER2低表达人群后线治疗可选用T-DXd，但也注明该依据来自于小样本数据[22]，提示循证等级有限。 SG和T-DXd的治疗适应症存在重叠，尚不能确定最佳的用药顺序策略。一项大型网状荟萃分析纳入33项2线及后线治疗的临床研究（合计11321例患者），根据优选概率排名曲线（SUCRA）计算结果，SG在所有研究终点上都优于其他单药治疗，在HER2低表达转移性TNBC人群中，T-DXd与SG疗效相似，但PFS和OS指标的改善次于SG，提示SG可能为晚期TNBC的最佳单药治疗方案[26]。ESMO-MCBS在线指南和2023 ESMO HER2低表达共识均明确推荐，对于HER2低表达晚期乳腺癌一线化疗失败后，HR阳性应优先考虑T-DXd，HR阴性（即TNBC）应首先考虑SG[27-28]。由此，晚期TNBC临床治疗格局已经焕然一新，正式进入了全新时代。此外，ADC的用药顺序与其治疗耐药性息息相关，肿瘤细胞抗原靶点和/或药载靶点的分子改变均可介导对ADC的耐药性[29]，临床实践中为减少交叉耐药性，应尽量避免选择具有抗原靶点或药载靶点的药物进行序贯治疗。ASCENT研究中，SG针对难治性（新辅助/辅助化疗后≤12个月复发）患者仍有一致的疗效获益，为了尽可能减少交叉耐药对患者的不利影响，临床仍需重视当前指南对SG 2线治疗的首选定位，避免过度延迟启用SG治疗。 TNBC领域ADC联合治疗研究及前序拓展 ADC类药物相较于传统化疗具有更好的靶向性，使其疗效和毒副作用均表现更优，因此有望成为联合治疗的新选择。在ADC联合免疫治疗方面，Ib/II期MORPHEUS-panBC研究显示，SG联合阿替利珠单抗用于未接受过系统治疗的PD-L1+、不可手术的局部晚期或转移性TNBC患者，ORR达66.7%，显示了积极的一线治疗潜力[30]；在联合靶向治疗方面，SEASTAR研究初步探索了SG联合PARP抑制剂瑞卡帕尼（Rucaparib）的疗效，结果所有３例PARP经治后疾病进展的患者出现部分缓解[31]。此外，ADC在TNBC领域的应用线序将继续前移，ASCENT-03和ASCENT-04试验均包含部分未经治疗的晚期TNBC患者，前者比较SG与TPC方案的疗效，后者比较SG联合帕博利珠单抗与化疗联合帕博利珠单抗的一线疗效；已报道的NeoSTAR研究则显示，SG用于TNBC新辅助治疗的病理完全缓解（pCR）率达30%，ORR达64%[32]；III期SASCIA及ASCENT-05研究将进一步探讨SG用于新辅助治疗后高复发风险的TNBC患者。期待这些研究能够进一步改变TNBC的临床治疗格局。总结和展望 TNBC是治疗预后较差的乳腺癌亚型，存在巨大的未被满足的临床治疗需求。近年来，ADC药物在mTNBC治疗中取得了显著进展，尤其是T-DXd、SG的出现，改变了晚期TNBC的临床实践。其中，SG已被多个国内外指南推荐为mTNBC二线治疗的首选方案；T-DXd也被指南推荐应用于HER2低表达的TNBC。随着ADC在晚期TNBC取得突破性进展，未来的研究探索和临床应用将得到进一步拓展，包括晚期一线治疗、早期新辅助和辅助治疗的研究正在开展中。SG此类新型ADC，有望成为TNBC的治疗基石，为改善患者预后带来新的希望。参考文献上下滑动查看更多内容 [1]Li C Y, Zhang S, Zhang X B, et al. 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Trastuzumab Deruxtecan in Previously Treated HER2-Low Advanced Breast Cancer [J]. N Engl J Med, 2022, 387(1): 9-20. DOI:10.1056/NEJMoa2203690. [18]Mosele F, Deluche E, Lusque A, et al. Trastuzumab deruxtecan in metastatic breast cancer with variable HER2 expression: the phase 2 DAISY trial [J]. Nat Med, 2023, 29(8): 2110-2120. DOI:10.1038/s41591-023-02478-2 [19]Krop I E, Masuda N, Mukohara T, et al. Patritumab Deruxtecan (HER3-DXd), a Human Epidermal Growth Factor Receptor 3-Directed Antibody-Drug Conjugate, in Patients With Previously Treated Human Epidermal Growth Factor Receptor 3-Expressing Metastatic Breast Cancer: A Multicenter, Phase I/II Trial [J]. J Clin Oncol, 2023: Jco2300882. DOI:10.1200/jco.23.00882. [20]Wu J, Zhang J, Li H, et al. 381O First-in-human/phase I trial of HS-20089, a B7-H4 ADC, in patients with advanced solid tumors [J]. Annals of Oncology, 2023, 34. DOI:10.1016/j.annonc.2023.09.558. [21]Tsai M, Han H S, Montero A J, et al. 259P Weekly ladiratuzumab vedotin monotherapy for metastatic triple-negative breast cancer [J]. Annals of Oncology, 2021, 32: S474-S475. DOI:10.1016/j.annonc.2021.08.542 [22]中国抗癌协会乳腺癌专业委员会, 中华医学会肿瘤学分会乳腺肿瘤学组, 邵志敏. 中国抗癌协会乳腺癌诊治指南与规范(2024年版) [J]. 中国癌症杂志, 2023, 33(12): 1092-1186. DOI:10.19401/j.cnki.1007-3639.2023.12.004 [23]Gradishar W J, Moran M S, Abraham J, et al. NCCN Guidelines® Insights: Breast Cancer, Version 4.2023 [J]. J Natl Compr Canc Netw, 2023, 21(6): 594-608. DOI:10.6004/jnccn.2023.0031. [24] 中国临床肿瘤学会乳腺癌专家委员会. 中国临床肿瘤学会（CSCO）乳腺癌诊疗指南2023 [M]. 北京: 人民卫生出版社, 2023 [25]Im S A, Gennari A, Park Y H, et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer [J]. ESMO Open, 2023, 8(3): 101541. DOI:10.1016/j.esmoop.2023.101541 [26]Schettini F, Venturini S, Giuliano M, et al. Multiple Bayesian network meta-analyses to establish therapeutic algorithms for metastatic triple negative breast cancer [J]. Cancer Treat Rev, 2022, 111: 102468. DOI:10.1016/j.ctrv.2022.102468. [27]Curigliano G, Castelo-Branco L, Gennari A, et al. ESMO Metastatic Breast Cancer Living Guidelines | ESMO [Z]. https://www.esmo.org/living-guidelines/esmo-metastatic-breast-cancer-living-guideline/triple-negative-breast-cancer. [28]Tarantino P, Viale G, Press M F, et al. ESMO expert consensus statements (ECS) on the definition, diagnosis, and management of HER2-low breast cancer [J]. Ann Oncol, 2023, 34(8): 645-659. DOI:10.1016/j.annonc.2023.05.008 [29]Coates J T, Sun S, Leshchiner I, et al. Parallel Genomic Alterations of Antigen and Payload Targets Mediate Polyclonal Acquired Clinical Resistance to Sacituzumab Govitecan in Triple-Negative Breast Cancer [J]. Cancer Discov, 2021, 11(10): 2436-2445. DOI:10.1158/2159-8290.Cd-21-0702 [30]Peter Schmid, et al. Interim analysis (IA) of the atezolizumab (atezo) + sacituzumab govitecan (SG) arm in patients (pts) with triple-negative breast cancer (TNBC) in MORPHEUS-pan BC: A Phase Ib/II study of multiple treatment (tx) combinations in pts with locally advanced/metastatic BC (LA/mBC). 2024 ESMO BC abstract 181O. [31]Yap T A, Hamilton E, Bauer T, et al. Phase Ib SEASTAR Study: Combining Rucaparib and Sacituzumab Govitecan in Patients With Cancer With or Without Mutations in Homologous Recombination Repair Genes [J]. JCO Precision Oncology, 2022, (6): e2100456. DOI:10.1200/po.21.00456 [32]Spring LM, Tolaney SM, Fell G, et al. Response-guided neoadjuvant sacituzumab govitecan for localized triple-negative breast cancer: results from the NeoSTAR trial. Ann Oncol. 2024 Mar;35(3):293-301. doi: 10.1016/j.annonc.2023.11.018. Epub 2023 Dec 12. PMID: 38092228. 王树森教授中山大学附属肿瘤医院乳腺癌单病种首席专家教授、主任医师、博士生导师国家肿瘤质控中心乳腺癌质控专业委员会委员中国乳腺癌筛查与早诊早治指南专家委员会委员国家卫健委乳腺癌合理用药指南专家委员会委员中国研究型医院协会乳腺癌专业委员会副主任委员中国抗癌协会肿瘤内分泌专委会副主任委员中国抗癌协会乳腺癌专业委员会常务委员中国临床肿瘤协会乳腺癌专业委员会常务委员广东省抗癌协会化疗专业委员会主任委员广东省胸部肿瘤防治研究会乳腺癌专业委员会主任委员广东省抗癌协会乳腺癌专业委员会副主任委员广东省南方肿瘤临床研究协会乳腺癌专委会副主委委员广东省医师协会乳腺专科工作委员会副主任委员（来源：《肿瘤瞭望》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

抗体药物偶联物临床结果多肽偶联药物免疫疗法

100 项与芦卡帕利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	芦卡帕利	L01XX	DB12332

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
输卵管癌	欧盟	Pharma& Schweiz GmbH	2023-11-30
输卵管癌	冰岛	Pharma& Schweiz GmbH	2023-11-30
输卵管癌	列支敦士登	Pharma& Schweiz GmbH	2023-11-30
输卵管癌	挪威	Pharma& Schweiz GmbH	2023-11-30
卵巢上皮癌	欧盟	Pharma& Schweiz GmbH	2023-11-30
卵巢上皮癌	冰岛	Pharma& Schweiz GmbH	2023-11-30
卵巢上皮癌	列支敦士登	Pharma& Schweiz GmbH	2023-11-30
卵巢上皮癌	挪威	Pharma& Schweiz GmbH	2023-11-30
原发性腹膜癌	欧盟	Pharma& Schweiz GmbH	2023-11-30
原发性腹膜癌	冰岛	Pharma& Schweiz GmbH	2023-11-30
原发性腹膜癌	列支敦士登	Pharma& Schweiz GmbH	2023-11-30
原发性腹膜癌	挪威	Pharma& Schweiz GmbH	2023-11-30
BRCA突变去势抵抗性前列腺癌	美国	Pharma& Schweiz GmbH	2020-05-15
BRCA突变去势抵抗性前列腺癌	美国	pharmaand GmbH	2020-05-15
铂敏感性卵巢上皮癌	欧盟	Pharma& Schweiz GmbH	2018-05-23
铂敏感性卵巢上皮癌	冰岛	Pharma& Schweiz GmbH	2018-05-23
铂敏感性卵巢上皮癌	列支敦士登	Pharma& Schweiz GmbH	2018-05-23
铂敏感性卵巢上皮癌	挪威	Pharma& Schweiz GmbH	2018-05-23
铂敏感性输卵管癌	欧盟	Pharma& Schweiz GmbH	2018-05-23
铂敏感性输卵管癌	冰岛	Pharma& Schweiz GmbH	2018-05-23

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
铂敏感性卵巢癌	临床3期	美国	Bristol Myers Squibb Co.	2022-01-30
铂敏感性卵巢癌	临床3期	美国	Clovis Oncology UK Ltd.	2022-01-30
铂敏感性卵巢癌	临床3期	美国	The Gynecologic Oncology Group	2022-01-30
铂敏感性卵巢癌	临床3期	美国	European Society of Gynaecological Oncology	2022-01-30
透明细胞腺癌	临床3期	德国	Clovis Oncology, Inc.	2020-06-08
子宫内膜样癌	临床3期	德国	Clovis Oncology, Inc.	2020-06-08
卵巢透明细胞癌	临床3期	德国	Clovis Oncology, Inc.	2020-06-08
铂类耐药性原发性腹膜癌	临床3期	德国	Clovis Oncology, Inc.	2020-06-08
转移性去势抵抗性前列腺癌	临床3期	美国	Pharma& Schweiz GmbH	2017-06-13
转移性去势抵抗性前列腺癌	临床3期	澳大利亚	Pharma& Schweiz GmbH	2017-06-13

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03522246 (GOG-3020 \| ATHENA-MONO (GOG-3020/ENGOT-ov45) \| ATHENA-MONO/GOG-3020/ENGOT-ov45 \| ATHENA-MONO \| GOG-3020/ENGOT-ov45 \| ATHENA–MONO \| ENGOT-ov45 \| ATHENA-COMBO \| ATHENA, CTgov)	临床3期	原发性腹膜癌 \| 卵巢上皮癌 \| 输卵管癌	1,097	Placebo+Rucaparib (Arm B: Rucaparib + Placebo)	鑰艱壓淵願網築鑰遞膚(淵鹽蓋繭顧壓獵憲齋觸) = 願廠鹽鹹觸淵齋糧網網積積壓鑰繭鬱顧壓廠鬱 (蓋襯膚願選鹽糧範觸積, 鏇齋積糧糧餘餘繭夢齋 ~ 夢簾夢壓鬱衊衊憲鹹構) 更多	-	2025-06-24
				Placebo (Arm D: Placebo + Placebo)	鑰艱壓淵願網築鑰遞膚(淵鹽蓋繭顧壓獵憲齋觸) = 選顧蓋願襯繭鑰壓製鏇積積壓鑰繭鬱顧壓廠鬱 (蓋襯膚願選鹽糧範觸積, 製醖製築製衊蓋鹽憲獵 ~ 網鹹膚製鑰構衊選窪憲) 更多
NCT02975934 (TRITON3, ASCO2025)	临床3期	转移性去势抵抗性前列腺癌 BRCA mutation status	-	Rucaparib 600 mg BID	遞鏇窪餘艱繭衊鑰廠獵(築窪願醖鑰鹽選築獵顧): HR = 0.52 (95% CI, 0.32 ~ 0.84) 更多	积极	2025-05-30
				Physician’s choice of docetaxel or ARPI
NCT04171700 (LODESTAR, ASCO2025)	临床2期	BRCA1 \| BRCA2 \| PALB2 ... 更多	-	Rucaparib monotherapy	餘積築鹹遞衊廠觸築獵(艱獵製糧壓襯鏇糧憲簾) = 餘醖夢鏇築餘襯衊壓鹹齋蓋獵範淵餘遞簾憲繭 (觸繭範繭夢淵獵憲積襯, 10 ~ 30) 更多	积极	2025-05-30
NCT02952534 (TRITON2, ASCO2025)	临床2期	转移性去势抵抗性前列腺癌 hypermethylated tumor DNA	277	Rucaparib	獵遞簾蓋廠齋選積壓夢(艱醖繭艱齋鏇願廠淵選) = 壓鏇襯艱糧艱鹹觸繭淵繭膚膚範壓醖網網顧醖 (製淵網淵壓積餘顧鏇鏇 )	积极	2025-05-30
NCT03694262 (EndoBARR, CTgov)	临床2期	子宫癌肉瘤 \| 子宫内膜癌 \| 复发性子宫内膜癌 ... 更多	30	Rucaparib+Atezolizumab+Bevacizumab	廠糧觸艱壓構鏇憲憲鹹 = 築遞艱膚構膚願壓鑰淵餘鹹蓋壓夢觸觸膚鏇憲 (築簾醖鬱壓鑰襯壓衊壓, 製範淵積壓鏇選網憲襯 ~ 蓋繭範簾餘鹽築積遞鏇) 更多	-	2025-05-30
Phase II study of rucaparib and nivolumab in patients with leiomyosarcoma (AACR2025)	临床2期	平滑肌肉瘤 BRCA mutations \| PD-1	-	Rucaparib	遞願鹹窪鑰夢夢憲鹹鹽(積襯遞餘鹽窪積鏇網鹹) = 窪製選齋夢簾獵遞憲餘獵襯鏇壓獵遞獵選鏇構 (蓋築醖願糧築遞鬱衊觸 ) 更多	积极	2025-04-28
				Nivolumab	遞願鹹窪鑰夢夢憲鹹鹽(積襯遞餘鹽窪積鏇網鹹) = 夢繭淵襯觸醖顧遞齋淵獵襯鏇壓獵遞獵選鏇構 (蓋築醖願糧築遞鬱衊觸 ) 更多
NCT02975934 (TRITON3, ASCO_GU2025) 人工标引	临床3期	转移性去势抵抗性前列腺癌 ATM Mutation (Deleterious) \| BRCA Mutation (Deleterious)	810	Rucaparib (BRCA)	選獵醖鹹艱構衊願網醖(網憲願餘觸願簾醖壓構) = 鬱襯艱顧獵餘餘餘鹽餘鏇襯觸鑰觸遞獵選簾醖 (襯網構簾簾衊繭築鏇遞 )	积极	2025-02-13
				Rucaparib (ITT)	選獵醖鹹艱構衊願網醖(網憲願餘觸願簾醖壓構) = 襯壓衊蓋壓蓋衊積製觸鏇襯觸鑰觸遞獵選簾醖 (襯網構簾簾衊繭築鏇遞 )
NCT02855944 (ARIEL4, Pubmed \| Lancet Oncol)	临床3期	复发性卵巢癌 BRCA1 \| BRCA2	349	Rucaparib	範觸鹽網選蓋廠簾範簾(廠醖遞觸積製廠網鑰觸) = Ten treatment-related deaths were reported in the rucaparib group, two of which were linked to judged to be related to rucaparib (cardiac disorder and myelodysplastic syndrome), and one death related to treatment was reported in the chemotherapy group, with no specific cause linked to the treatment 夢淵積鹹鹽蓋窪醖積餘 (獵範窪鑰醖膚遞鑰範餘 )	不佳	2025-02-01
				Chemotherapy
ESMO_ASIA2024 人工标引	N/A	BRCA 突变卵巢癌 \| HRD 阳性卵巢癌维持 \| 一线同源重组修复缺陷	46	Olaparib/Rucaparib	壓範襯鬱獵觸遞築範蓋(鹹顧窪獵襯膚獵鏇製願) = 蓋蓋選鏇鏇齋範襯築壓餘築憲鑰網憲選鹽淵繭 (積積壓顧範製壓顧蓋獵 ) 更多	积极	2024-12-07