The purpose of this study is to learn about the safety and tolerability of Cirtuvivint in combination with Olaparib in platinum resistant ovarian cancer. The study also aims to determine the recommended dose of the combination therapy.
If a participant is a good fit for the study, and they enroll in the study, they will:
* Visit the clinic often at the beginning of the study for physical exams, blood draws, vital signs, and other study and routine care procedures. After the first two months participants will visit the clinic every 28 days.
* Take the study medications, Cirtuvivint and Olaparib. Participants will take Olaparib every day. Participants will either take Cirtuvivint 5 days per week or 2 days per week.

开始日期2025-12-01

申办/合作机构

University of Colorado Denver

[+2]

NCT05128734

/ Not yet recruiting临床2期IIT

A Randomized Phase II Study of Temozolomide Monotherapy or in Combination With Olaparib in Patients With METHYLATED 06-Methylguanine-DNA Methyltransferase (MGMT) Pre-Treated Triple Negative Breast Cancer (TNBC)

This is a randomized phase II study to evaluate the disease control rate (DCR) of patients with metastatic or locally advanced METHYLATED 06-methylguanine-DNA methyltransferase (MGMT) with triple-negative breast cancer (TNBC) treated with Temozolomide ± Olaparib. Patients will be randomized 1:1 to Treatment Arm 1 (temozolomide treatment) or Arm 2 (temozolomide plus olaparib treatment).

开始日期2025-09-01

申办/合作机构

AHS Cancer Control Alberta

NCT07024784

/ Not yet recruiting临床2期

A Phase 1b Dose Escalation and Expansion Study of IMGN151 as Monotherapy and in Combination With Other Anti-Cancer Therapies in Subjects With Gynecologic Cancers

Cancer is a condition where cells in a specific part of body grow and reproduce uncontrollably. The purpose of this study is to assess safety and tolerability of IMGN151 when given as monotherapy and in combination with other anti-cancer therapies in adult participants with gynecologic cancers.
IMGN151 is an investigational drug being developed for the treatment of gynecologic cancers. Participants are placed in 1 of 4 groups, called treatment arms. Each group receives a different treatment. Around 350 participants with gynecologic cancers will be enrolled in the study at approximately 50 sites worldwide.
Participants will receive intravenous infusions of IMGN151 as monotherapy or in combination with anti-cancer therapies according to their assigned study arm. In Arm A, participants will receive IMGN151 in combination with carboplatin on Day 1 of each cycle. In Arm B, participants will receive IMGN151 in combination with olaparib, twice a day (BID) on Day 1 of each cycle. In Arm C, participants will receive IMGN151 in combination with bevacizumab on Day 1 of each cycle. In Arm D, participants will receive IMGN151 as monotherapy on Day 1 of each cycle. The total study duration will be approximately 3 years.
There may be higher treatment burden for participants in this trial compared to their standard of care. Participants will attend regular visits during the study at a hospital or clinic and may require frequent medical assessments, blood tests, and scans.

开始日期2025-07-15

申办/合作机构

AbbVie, Inc.

100 项与奥拉帕利相关的临床结果

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100 项与奥拉帕利相关的转化医学

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100 项与奥拉帕利相关的专利（医药）

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4,879

项与奥拉帕利相关的文献（医药）

2025-12-31·INTERNATIONAL JOURNAL OF HYPERTHERMIA

Addition of PARP1-inhibition enhances chemoradiotherapy and thermoradiotherapy when treating cervical cancer in an in vivo mouse model

Article

作者: van Bochove, Gregor G. W. ; Rodermond, Hans M. ; Oei, Arlene L. ; Krawczyk, Przemek M. ; Stalpers, Lukas J. A. ; Franken, Nicolaas A. P. ; Scutigliani, Enzo M. ; Mei, Xionge ; Crezee, Johannes ; IJff, Marloes

Background: Efficacy of current treatment options for cervical cancer require improvement. Previous in vitro studies have shown the enhancing effects of the addition of PARP1-inhibitors to chemoradiotherapy and thermoradiotherapy. The aim of our present study was to test efficacy of different combinations of treatment modalities radiotherapy, cisplatin, hyperthermia and PARP1-inhibitors using in vitro tumor models, ex vivo treated patient samples and in vivo tumor models.Materials and Methods: In vitro clonogenic survival curves (0-6 Gy) show that PARP1-i (4-5 M Olaparib) enhances both chemoradiotherapy (0.3-0.5 µM cisplatin) and thermoradiotherapy (42 °C for 1 h) in SiHa, CaSki and HeLa cells. A cervical cancer mouse model and freshly obtained in-house developed patient-derived organoids were used to examine the effects of different treatment combinations. For the in vivo study, human cervical cancer (SiHa) cells were injected in the right hind leg of athymic nude mice. In vivo mouse experiments show that PARP1-i enhances thermoradiotherapy or chemoradiotherapy by reduction of tumor volumes. Five cycles of treatment were applied with the following doses per cycle: irradiation 3 Gy, hyperthermia 1 h at 42 °C, cisplatin at 2 mg/kg, and twice PARP1-i at 50 mg/kg.Results: Quadruple treatment, combining radiotherapy, hyperthermia, cisplatin and PARP1-i, was very effective but also lead to severe side effects causing severe weight loss and death. In contrast, thermoradiotherapy or chemoradiotherapy with addition of PARP1-i, were effective without serious side effects.Conclusion: The triple combinations are promising options for potentially more effective treatment of locally advanced cervical cancer without more toxicity.

2025-12-31·ANNALS OF MEDICINE

Haematologic outcomes and associated clinical characteristics among patients receiving Olaparib therapy in the UAE: a retrospective chart review

Article

作者: Akour, Amal ; Nabil, Said ; Ibrahim, Mariam ; Kendakji, Saba ; ZainAlAbdin, Sham ; Aburuz, Salahdein ; Wahba, Lina

BACKGROUND:

Poly ADP ribose polymerase (PARP) inhibitors, such as Olaparib (Lynparza^®), are pivotal in treating certain cancers, particularly those linked to BReast CAncer gene (BRCA) mutations. Despite its established efficacy, Olaparib use is associated with various adverse events (AEs), notably haematologic toxicities, such as anaemia. This retrospective chart review study aimed to examine haematologic outcomes and associated factors in patients treated with Olaparib at a tertiary hospital in the UAE.

METHODS:

We reviewed the medical charts of patients prescribed Olaparib and focused on haematologic indices at a baseline of 1-month, 3-month and 6-month follow-up periods. Data were analysed to determine the AEs frequency, transfusions need and potential associated patients' clinical characteristics.

RESULTS:

This study included all patients who received Olaparib (n = 66). Most patients were females (n = 61; 92.4%) and the vast majority were non-smokers (97%) and free of hepatic disease. Themean age of the patients was 57.03-year-old (SD) = 12.06 years), and body mass index (BMI) was 28.16 (SD = 6.40) kg/m². A high rate of anaemia (70.8%) was detected among the patients during their Olaparib therapy. Approximately, one-third of the patients developed neutropenia and thrombocytopenia. Transfusion was needed in almost half of the patients. Glomerular filtration rate (GFR) and neutropenia were significantly correlated with moderate-severe anaemia (OR = 0.097, 95% CI: 0.011-0.88, p value = .038) and (OR = 9.04, 95% CI: 1.024-79.78, p value = .048), respectively.

CONCLUSIONS:

Our findings highlight the side effects of Olaparib therapy in terms of haematology which could be avoided. Further studies are needed to better understand the therapeutic management of Olaparib and the mitigation of haematologic complications.

2025-10-01·COMPUTATIONAL BIOLOGY AND CHEMISTRY

The drug discovery candidate for targeting PARP1 with Onosma. Dichroantha compounds in triple-negative breast cancer: A virtual screening and molecular dynamic simulation

Article

作者: Mishra, Anurag ; Chandra, Muktesh ; Hamad, Atheer Khdyair ; Jawad, Mahmood Jasem ; Taher, Waam Mohammed ; Kareem, Radhwan Abdul ; Verma, Lokesh ; Prasad, G V Siva ; Alwan, Mariem ; Ahmed, Hanan Hassan ; Saadh, Mohamed J

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by the overexpression of poly-ADP ribose polymerase 1 (PARP1), a key enzyme in DNA repair. Targeting PARP1 with inhibitors presents a promising therapeutic strategy, particularly given the limited treatment options for TNBC. This study employed in silico methodologies to evaluate the pharmacokinetic and inhibitory potential of FDA-approved drugs and compounds derived from Onosma. dichroantha root extracts against PARP1. Virtual screening and molecular docking identified Midazolam, Olaparib, Beta-sitosterol, and 1-Hexyl-4-nitrobenzene as top candidates, exhibiting strong binding affinities of -10.6 kcal/mol, -9.9 kcal/mol, -6.83 kcal/mol, and -5.53 kcal/mol respectively. Molecular dynamics simulations (MDS) over 100 nanoseconds revealed that Beta-sitosterol formed the most stable complex with PARP1, demonstrating minimal structural deviations and robust hydrogen bonding. The Molecular Mechanics-Poisson-Boltzmann Surface Area (MM-PBSA) analysis further confirmed Beta-Sitosterol and Olaparib superior binding free energy (ΔG_bind= -175.43 kcal/mol and -180.8 kcal/mol respectively), highlighting its potential as a potent PARP1 inhibitor. ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiling indicated that Beta-Sitosterol adheres to Lipinski's Rule of Five, with high intestinal absorption (95.88 %) and blood-brain barrier permeability (0.824), despite low water solubility. Protein-protein interaction analysis identified key PARP1-associated proteins, including CASP3, CASP7, and XRCC1, suggesting broader therapeutic implications. These findings underscore the potential of Beta-Sitosterol as a novel PARP1 inhibitor for TNBC treatment, combining computational validation with favorable pharmacokinetic properties. The study also highlights the utility of drug repurposing and plant-derived compounds in developing targeted therapies for TNBC, paving the way for further preclinical and clinical investigations.

1,282

项与奥拉帕利相关的新闻（医药）

2025-07-12

·ioncology

European Urology丨PARP抑制剂治疗mCRPC的疗效异质性分析

点击蓝字，关注我们编者按：前列腺癌治疗中，转移性去势抵抗性前列腺癌（mCRPC）的PARP抑制剂（PARPi）疗效异质性备受关注。《European Urology》的一项研究综合分析了13项试验（4278例患者），发现BRCA变异患者通过PARP抑制剂治疗拥有最大获益，PALB2或CDK12变异患者有明显获益，而ATM或CHEK2变异患者没有获益。01研究背景mCRPC的治疗需综合考虑临床和患者个体因素，现有方案包括化疗、雄激素受体通路抑制剂（ARPI）、PARPi、放射性药物和免疫治疗等。然而，PARPi在mCRPC中的最佳治疗策略仍具挑战，同时临床试验设计存在差异及证据的快速更新，需要更精准的疗效评估。同源重组修复（HRR）通路检测是指导PARPi治疗的标准。HRR通路负责DNA双链断裂修复，其核心基因（如BRCA1/2、ATM、PALB2等）突变会导致修复功能缺陷。HRR缺陷使肿瘤依赖PARP1修复DNA，对PARPi敏感。美国FDA已批准奥拉帕利和卢卡帕利用于HRR基因突变患者，但不同监管机构审批范围不同（如欧洲仅批准BRCA阳性患者）。现有3期临床试验对PARPi联合ARPI的疗效报道不一。PROpel和TALAPRO-2显示，PARPi+ARPI在整体人群中改善无进展生存（PFS），HRR阳性亚组获益更显著；而MAGNITUDE试验仅在HRR阳性队列中观察到PFS获益。这种差异可能源于试验设计（如前瞻性分层HRR状态）、药物组合（不同PARPi与ARPI协同效应）及患者基线（如既往ARPI暴露）。随着新型疗法和分子检测技术发展，临床证据快速迭代，传统静态系统评价难以实时整合动态数据。临床亟需动态、交互式的证据合成工具，以直观呈现不同基因突变亚组的疗效差异，指导个体化治疗。因此，本研究通过动态系统评价整合关键研究，量化分析PARPi单药及联合ARPI在不同HRR基因突变mCRPC中的疗效差异，结果通过交互式网站实时更新，助力临床决策。02研究方法通过MEDLINE和EMBASE数据库检索从建库开始至2021年6月16日的文献，关键词包括“PARP抑制剂”“mCRPC”“HRR基因突变”等，并通过“监测模块”每周自动更新文献。纳入标准为评估PARPi单药治疗经治mCRPC或联合ARPI治疗初治mCRPC的临床试验，初治定义为未接受过mCRPC系统治疗或治疗后进展者。经标题、摘要及全文筛选，最终纳入13项试验（4278例患者），其中7项为单药研究，6项为联合治疗研究。使用交互式图形用户界面结合机器辅助注释工具（“提取模块”）提取数据，内容包括患者基线特征（如年龄、突变类型）、疗效终点（总生存、影像学无进展生存、客观缓解率等）及安全性数据（如≥3级不良事件）。采用Cochrane偏倚风险工具评估随机对照试验，非随机研究参考相应指南评估，结果显示多数试验偏倚风险较低。预设亚组包括HRR突变状态、BRCA状态及单个基因（如BRCA1、BRCA2、ATM等）。对于PARPi单药治疗试验，因随访时间异质性，采用每百人月事件发生率评估肿瘤应答，公式为“事件数/(患者数×中位随访月数)×100”。联合治疗的生存结局采用风险比（HR），二分类结局采用相对风险（RR），均通过DerSimonian-Laird随机效应模型合并。比较PARPi单药或联合ARPI与对照组的不良事件发生率，重点分析血液学毒性。研究结果通过动态证据网站（https://parp.living-evidence.com/）实时更新，用户可筛选基因类型、治疗线数等参数，可视化疗效曲线并下载个性化证据摘要，辅助临床决策。03研究结果截至2024年7月1日（分析截止日期），13项涉及4278例患者的临床试验（37篇文献）符合纳入标准（图1）。图1. 研究流程图3.1 PARPi单药治疗七项试验（18篇文献）评估了PARPi单药治疗既往接受过治疗的mCRPC患者的情况，共纳入了1459例患者。其中2项为3期试验，其余为2期试验。除3项试验外，其余均为单臂研究。3项试验评估了奥拉帕利，2项试验评估了卢卡帕利，各有1项试验分别评估了他拉唑帕利和尼拉帕利。试验中中位随访时间的四分位距为11.5-19个月。符合条件的试验中基因改变的频率分布见图2。大多数领域的试验偏倚风险较低（TOPARP-A试验中通过回顾性方法确定假定生物标志物）。图2. PARP抑制剂试验中基因改变的合并频率（*纳入试验中报告的具有特定基因突变的试验数量和患者数量。）不同基因变异状态的疗效结果在试验中报道较少且不一致。由于两项试验中既往治疗的使用和对照臂存在异质性，因此未使用PROfound和TRITON3试验的数据进行成对比较的荟萃分析。3.1.1 肿瘤应答异质性BRCA突变亚组：BRCA1/2突变患者的肿瘤应答率显著高于其他基因亚组。其中，BRCA2突变患者的PSA50%应答率为3.3/100人月（95% CI 2.3-4.4），客观缓解率（ORR）3.3/100人月；BRCA1突变患者PSA50%应答率1.2/100人月，ORR 2.0/100人月。非BRCA HRR突变亚组：PALB2突变患者PSA50%应答率3.3/100人月；而ATM（0.4/100人月）、CDK12（0.2/100人月）、CHEK2（1.0/100人月）突变患者应答率显著较低。影像学应答：BRCA2突变患者的影像学ORR为3.3/100人月，BRCA1为2.0/100人月，PALB2为1.4/100人月；ATM、CDK12、CHEK2突变患者ORR均低于1/100人月。图3. PARPi单药治疗在不同同源重组修复基因改变情况下的疗效差异其他基因的疗效结果在符合条件的试验中报告不一致。1/4的FANCA突变患者、1/2的BRIP1突变患者和1/1的RAD51B突变患者出现PSA50%缓解。1/4的FANCA突变患者出现完全缓解。每人-月发生率是衡量特定事件在人群中随时间发生频率的指标。例如，仅携带BRCA2突变的患者中，PSA50%缓解率为每100人月3.3例。这意味着，若随访100例BRCA2突变患者1个月，或10例患者10个月，可观察到3.3例PSA50%缓解（PSA50%=前列腺特异性抗原缓解50%）。3.1.2 生存结局影像学进展率：BRCA1/2突变患者的影像学进展率为2.5/100人月（95% CI 1.3-3.7），显著低于ATM突变患者的3.6/100人月（95% CI 0.5-6.6）。全因死亡率：BRCA1/2突变患者死亡率3.4/100人月（95% CI 1.4-5.5），ATM突变患者为3.6/100人月（95% CI 1.6-5.6），提示BRCA突变患者生存优势。3.1.3 安全性PARPi单药的≥3级不良事件（AE）发生率为4.4/100人月（95% CI 1.9-6.8），常见血液学毒性包括贫血、血小板减少；任何级AE发生率7.1/100人月（95% CI 3.3-11），非血液学毒性以疲劳、恶心为主。3.1.4 基因频率与疗效关联HRR基因突变频率在纳入试验中差异显著（图2）：BRCA2突变占42%（1093例），ATM占5%（545例），CDK12占7%（263例），PALB2占6%（180例）。疗效异质性与基因功能相关：BRCA2/PALB2作为HRR核心修复基因，突变后对PARPi敏感性更高；ATM作为DNA损伤传感器，突变后未显著影响PARP依赖。3.2 PARPi+ARPI联合治疗在系统评价纳入的研究中，3项2期试验（3篇文献）评估了PARP抑制剂（PARPi）联合雄激素受体通路抑制剂（ARPI）治疗（奥拉帕利+阿比特龙、尼拉帕利+阿比特龙、维利帕利+阿比特龙）在至少接受过一种mCRPC系统治疗（包括紫杉类化疗和/或ARPI治疗）的患者中的疗效。由于研究设计和纳入标准存在显著异质性，这些试验未被纳入最终的定量荟萃分析。3项3期试验（16篇文献）评估了一线PARPi联合治疗在2501例mCRPC患者中的疗效（MAGNITUDE试验允许mCRPC患者在入组前接受<4个月的醋酸阿比特龙治疗）。其中，每项试验分别评估了奥拉帕利+阿比特龙、尼拉帕利+阿比特龙和他拉唑帕利+恩扎卢胺。这些试验被纳入最终的定量荟萃分析，试验中位随访时间的四分位间距为24.9–36.5个月。基线特征详情见表2。如补充图1所示，大多数领域的试验偏倚风险较低。图4总结了PARPi+ARPI在总体人群和各临床相关基因亚组中的疗效。图4. 临床相关亚组中PARP抑制联合雄激素受体通路抑制剂的疗效差异rPFS和OS的总体人群结果纳入了TALAPRO-2队列1的数据。MAGNITUDE试验中HRR阳性（HRR+）和阴性（HRR-）亚组的rPFS数据通过固定效应荟萃分析进行合并，以评估总体人群的rPFS。由于MAGNITUDE试验未报告HRR-亚组的OS结果，因此无法与HRR+亚组的OS数据合并分析。a 针对HRR+、BRCA+和BRCA-亚组的rPFS分析，采用了TALAPRO-2扩展队列的结果以扩大样本量。在PROpel试验中，所有HRR-患者均被纳入BRCA-亚组分析，HRR-亚组的分析使用了TALAPRO-2队列1的数据。b 对于OS分析，HRR+和BRCA+亚组使用了MAGNITUDE试验中经交叉治疗和后续治疗调整后的数据。此外，研究还进行了多项敏感性分析（如正文所述），相关结果见补充材料。c HRR-亚组的分析使用了TALAPRO-2队列1的数据，MAGNITUDE试验未提供HRR-亚组的OS数据。3.2.1 HRR状态与疗效HRR+亚组：PARPi+ARPI显著改善影像学无进展生存（rPFS），风险比（HR）0.54（95% CI 0.37-0.79），提示HRR缺陷患者获益更显著（图4A）；调整交叉治疗后，总生存（OS）HR 0.68（95% CI 0.55-0.85）。HRR-亚组：rPFS仍有改善（HR 0.74，95% CI 0.63-0.88），可能与PARPi抑制AR信号通路的协同效应相关。3.2.2 单个基因亚组分析BRCA突变：BRCA+患者rPFS获益最大（HR 0.28，95% CI 0.13-0.62），其中BRCA2（HR 0.19）和BRCA1（HR 0.12）突变均显著获益（图4B）；调整后OS HR 0.47（95% CI 0.31-0.71），提示BRCA突变是最强疗效预测因子。非BRCA基因：CDK12突变患者rPFS HR 0.58（95% CI 0.35-0.95），存在潜在获益；PALB2（HR 0.53）、ATM（HR 0.93）、CHEK2（HR 0.92）突变患者未观察到显著生存获益（图4C）。3.2.3 安全性联合治疗的≥3级AE风险显著高于ARPI单药（相对风险1.83，95% CI 1.11-3.01），主要为血液学毒性（如中性粒细胞减少）；5级AE发生率无显著差异。3.2.4 疗效预测因素基因功能差异：BRCA2/PALB2通过HRR通路直接参与DNA修复，突变后导致PARP依赖；CDK12突变可能通过转录-修复偶联机制增强PARPi敏感性。检测技术影响：血液ctDNA检测可能低估HRR突变频率（尤其低肿瘤负荷患者），导致部分HRR+患者被误分类至HRR-亚组。04讨论这项动态交互式荟萃分析全面定量总结了PARPi在mCRPC中的治疗效果，包括一线与ARPI联合使用，或在经治疾病中作为后线单药治疗的情况。我们利用临床试验的最新证据提供了精确的疗效评估，对具有临床重要性的亚组进行了更强的统计分析——此前由于样本量有限，各独立试验对这些亚组的分析大多未得出明确结论。结果表明，参与HRR通路的基因在引发对PARPi治疗的响应方面并非等效。最易对PARPi产生响应的基因组改变存在于BRCA2、PALB2、BRCA1和CDK12基因。我们的发现超越了“HRR”与“非HRR”的一般性指导，为临床医生提供了关于PARPi使用的更具体信息。在指导mCRPC患者合理使用PARPi方面，基于特定基因的方法似乎是最佳选择。1. BRCA突变的核心预测价值与生物学机制BRCA1/2突变患者在单药和联合治疗中均表现出最强的肿瘤应答和生存获益，其中BRCA2突变的疗效显著优于BRCA1。例如，BRCA2突变患者接受PARPi单药治疗时，PSA50%应答率达3.3/100人月，联合治疗rPFS的HR低至0.19，提示BRCA2缺陷通过完全失活HRR通路产生“合成致死”效应。BRCA1突变疗效较弱可能与双等位基因缺失比例较低（仅35%）和胚系突变频率少有关，其肿瘤细胞可能保留部分HRR功能，导致对PARPi敏感性下降。从生物学角度看，BRCA2直接参与DNA双链断裂的同源重组修复，其突变导致基因组高度不稳定，而PARPi通过捕获PARP1-DNA复合物加剧这种损伤。本研究首次通过动态数据整合证实，BRCA突变状态是PARPi疗效最可靠的预测因子，支持将BRCA1/2与其他HRR基因区分对待的临床策略。2. 非BRCAHRR基因的疗效异质性PALB2与CDK12的潜在获益：PALB2作为BRCA2的协同因子，其突变患者单药治疗应答率与BRCA2接近（PSA50%应答率3.3/100人月），但联合治疗因样本量小（30例）未达显著差异（HR=0.53）。CDK12突变在mCRPC中发生率14%，其通过转录-修复偶联机制影响DNA复制叉稳定性，联合治疗显示rPFS显著改善（HR=0.58），可能与PARP和ATR抑制剂的协同作用相关。ATM与CHEK2的耐药机制：ATM突变患者无论单药或联合治疗均无获益，因其作为DNA损伤传感器而非修复执行因子，突变后不会导致PARP依赖。CHEK2突变同样缺乏HRR通路核心功能，提示PARPi对非HRR修复缺陷肿瘤疗效有限。3. 联合治疗在HRR阴性患者中的作用机制尽管HRR阴性患者的rPFS改善幅度低于HRR阳性亚组（HR=0.74 vs 0.54），但其获益可能源于以下机制：①AR信号与PARP通路的协同抑制：PARP1可促进AR转录，联合治疗通过双重阻断增强抗肿瘤效应；②非HRR基因突变的贡献：约14%的mCRPC存在RB1、RNASEH2B等突变，可能通过替代途径增强PARPi敏感性；③检测技术的局限性：血液ctDNA可能漏检组织中的HRR突变（尤其低肿瘤负荷患者），导致部分HRR阳性患者被误分类至阴性亚组。4. 动态证据平台的临床应用与实践挑战本研究配套的交互式网站提供实时更新的基因特异性疗效数据，临床医生可输入患者突变类型（如BRCA2、CDK12），获取个性化的应答率、生存曲线及毒性风险评估。然而，实践中需注意：检测panel的覆盖范围：当前指南推荐检测至少12个HRR基因，但不同机构采用的检测panel差异显著（如FoundationOne vs 本地测序），可能导致漏检罕见突变（如FANCA）。治疗线数与药物选择：单药治疗适用于经治患者，而联合治疗更适合初治未接受ARPI的患者。例如，PROpel试验中联合治疗仅允许既往非mCRPC阶段的ARPI暴露，而MAGNITUDE要求初治患者，提示治疗顺序可能影响疗效。5. 研究优势与局限性优势：①采用LIvE动态框架整合13项试验（4278例患者），克服单个研究样本量不足的问题（如PALB2亚组仅30例）；②首次系统比较12个HRR基因的疗效差异，而非笼统的HRR阳性/阴性分类；③通过交互式平台实现证据透明化，支持用户探索原始数据和敏感性分析结果。局限性：①基因亚组样本量小，部分结果（如CHEK2）因统计效能不足需谨慎解读；②多数试验未报告种族/民族分层数据，无法评估遗传背景对疗效的影响；③OS数据受随访时间和后续治疗影响，仅MAGNITUDE提供调整后的分析，其他试验需进一步随访。6. 未来研究方向与临床启示生物标志物的精细化探索：需验证双等位基因缺失、胚系/体细胞突变对疗效的预测价值。例如，本研究发现双等位基因BRCA2突变患者的应答率比单等位基因高40%。新型联合疗法的开发：针对ATM突变患者，ATR抑制剂（如AZD6738）可能是更优选择，因其靶向DNA损伤应答通路的上游激酶。动态证据的临床转化：建议将本研究的基因特异性疗效数据纳入NCCN、EAU等指南更新，推动PARPi处方从“HRR泛筛”转向“核心基因优先”策略。05结论现有证据表明，对于携带BRCA突变的mCRPC患者，PARPi治疗可延缓疾病进展并改善OS，而PALB2和CDK12突变患者也显示出强烈的潜在获益信号。然而，携带CHEK2和ATM突变的患者无法从PARPi治疗中获益。▌参考文献：Syed Arsalan Ahmed Naqvi, I.B. Riaz, A. Bibi et al., Heterogeneity of the Treatment Effect with PARP Inhibitors in Metastatic Castration-resistant Prostate Cancer: A Living Interactive Systematic Review and Meta-analysis, Eur Urol (2025), https://doi.org/10.1016/j.eururo.2024.12.007（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。

放射疗法临床3期临床结果

2025-07-11

·BioArt

Cell | 引导编辑与深度学习结合实现ATM基因全部点突变的功能解析

撰文 | 木兰之枻大规模平行测序推动了遗传诊断的飞速发展，然而测序发现的众多意义未明变异（VUSs）仍是临床遗传学面临的重要挑战。这其中如何对ATM和BRCA1/2等大型基因的VUSs进行饱和高通量功能分析是当前亟待解决的关键难题【1】。ATM基因编码的蛋白是DNA损伤应答（DDR）通路的核心调控因子和重要抑癌因子，在维持应激条件下的细胞稳态中发挥关键作用。ATM基因的纯合致病性变异会导致共济失调毛细血管扩张综合征（A-T），而致病性杂合变异则会导致多种癌症风险增加。因此，ATM基因的遗传筛查在高风险人群和肿瘤常规筛查中都非常重要。除此之外，ATM功能缺失状态也被用于指导临床治疗：例如PARP抑制剂奥拉帕利（Olaparib）已被批准用于治疗携带ATM等同源重组修复基因缺失的转移性去势抵抗性前列腺癌【2-3】。综上可知，对ATM基因所有单核苷酸变异（SNVs）进行功能评估，在癌症风险预测、A-T疾病诊断、癌症治疗方案指定以及患者预后等方面均有非常重要的临床意义。目前而言，ATM变异的功能解析仍存在诸多困难，不同临床实验室对多种变异的解读存在显著分歧【4】。因此，如何建立新的研究策略，以对ATM基因所有SNVs进行全面系统的分析与评估，是当下研究的重点。2025年6月27日，韩国延世大学医学院的Hyongbum Henry Kim实验室在Cell杂志上发表了题为Functional assessment of all ATM SNVs using primeediting and deep learning的论文。文章整合引导编辑（primeediting）与深度学习算法，对ATM基因编码区所有变异的功能进行了系统性全面评估。通过将功能数据与现有临床数据整合分析，本研究验证了该评估体系在预测ATM变异携带者癌症易感性和患者预后方面的有效性。基于此，研究者还成功开发出预测模型DeepATM，可以准确预测ATM遗传变异的功能，为全面解析所有ATM基因SNVs的细胞效应提供了有力工具（Nat Biotechnol | 魏文胜团队系统揭秘人类基因组中“沉默突变”的功能性“低语”）。鉴于ATM缺失会导致细胞增殖和存活能力下降，研究者首先构建出ATM单倍体HCT116细胞以开展SNVs功能筛选分析。随后，研究者利用引导编辑结合奥拉帕利处理，对ATM基因55和56号外显子进行了初步的饱和突变筛选。该筛选证实，在ATM单倍体背景下结合奥拉帕利处理，能更有效区分并评估ATM基因SNVs的功能差异。研究者进一步构建了覆盖ATM基因全编码区的epegRNA文库，并在ATM单倍体细胞中进一步证实了奥拉帕利处理的必要性。随后的系统性功能评估可将ATM基因24534种SNVs分为无功能（即奥拉帕尼存在时细胞适应性丧失）、中等功能和功能变异三大类，其中前两类统称为“功能缺陷型变异体”。研究者还选取部分突变开展验证实验，有力证实了筛选策略的准确性和有效性。研究者还将功能评估结果与多种生物信息学预测工具进行比较分析，发现AlphaMissense及CADD与实验结果吻合度最高，但也仅呈现出中等水平的相关性，这凸显了实验验证的必要性。后续与PhyloP的关联分析发现，ATM基因进化保守区域对氨基酸改变的耐受性降低。此外，功能型SNV的BLOSUM氨基酸替换倾向性评分更高。对不同类型SNVs的分析发现，88%的无义突变和79%的剪接受体/供体位点突变属于无功能型变异，相比之下，仅30%内含子突变和20%错义突变属于无功能变异，这也与BAP1、VHL和DDX3X基因SNVs的分析结论一致。分析还指出，特定类型氨基酸替换如W>G/C/R/S/L、V>D、L>P/R、R>P、Y>D等高度有害，且非极性替换为带电氨基酸更易导致功能受损。研究者还深入探究了ATM基因SNVs功能评估结果的临床意义，证实了其与现有临床遗传变异分类结果的一致性。通过与人群变异频率数据库gnomAD的比较分析发现，无功能变异在普通人群中随进化选择而被自然淘汰。在UKB数据库中开展的癌症累积发病率分析发现，ATM功能分析结果为评估变异携带者的患癌风险提供了有力依据，其中携带无功能变异的个体面临更高的患癌风险。随后的乳腺癌患者数据库分析也证实了ATM功能评估体系的临床价值。基于功能评估结果，研究者还对ATM基因的多种SNVs进行了重新分类。研究者通过分析GENIE和gnomAD数据库中ATM基因错义突变的分布频率，证实了功能评估在分析ATM基因变异与癌症风险相关性的临床实用性。研究者还对慢性淋巴细胞白血病（CLL）和膀胱癌患者的基因组数据进行了分析，验证了SNVs功能评估预测癌症患者预后的能力。最后，基于建立的23092种ATM基因SNVs功能评估数据集，研究者开发了深度学习预测模型DeepATM，并对剩余4421种功能未注释的SNVs进行了预测。经UKB和GENIE数据队列的联合分析，研究者证实了DeepATM预测ATM基因SNVs功能的准确性和临床价值。总体而言，本研究基于引导编辑新技术和深度学习算法，首次实现了对ATM基因全编码区所有点突变的功能评估，并通过多重联合分析证实了点突变功能评估的准确性和临床应用价值。这一研究不仅建立了一个面向更多功能未知点突变的系统评估平台，也为后续遗传变异的功能及疾病诊疗探索提供了新的思路。原文链接https://doi.org/10.1016/j.cell.2025.05.046制版人：十一参考文献1.Yurgelun, M.B., et al. (2015). Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome13.e20. Gastroenterology 149, 604.2.de Bono, J., et al. (2020). Olaparib for MetastaticCastration-Resistant Prostate Cancer. N. Engl. J. Med. 382,2091–2102.3. Hussain, M., et al. (2020). Survival with Olaparib in Metastatic Castration-Resistant Prostate Cancer. N. Engl. J. Med. 383,2345–2357.4. Balman˜ a, J., et al.(2016). Conflicting Interpretation of Genetic Variants and Cancer Riskby Commercial Laboratories as Assessed by the Prospective Registry of Multiplex Testing. J. Clin. Oncol. 34, 4071–4078.学术合作组织（*排名不分先后）战略合作伙伴（*排名不分先后）·转载须知【非原创文章】本文著作权归文章作者所有，欢迎个人转发分享，未经作者的允许禁止转载，作者拥有所有法定权利，违者必究。转载须知【原创文章】BioArt原创文章，欢迎个人转发分享，未经允许禁止转载，所刊登的所有作品的著作权均为BioArt所拥有。BioArt保留所有法定权利，违者必究。BioArtMedPlants人才招聘近期直播推荐

临床研究

2025-07-09

·PRNewswire

Kazia Therapeutics Reports Early Efficacy Data from First Triple-Negative Breast Cancer Patient Receiving Paxalisib Combination Regimen achieving >50% Reduction in Circulating Tumor Cells in Phase 1b Trial

SYDNEY, July 9, 2025 /PRNewswire/ -- Kazia Therapeutics (NASDAQ: KZIA) is pleased to announce preliminary results from the first patient in its Phase 1b trial evaluating a combination regimen of Paxalisib, pembrolizumab (Keytruda®), and standard chemotherapy after completing Cycle 1 (21 days) of dosing. The patient, a 61-year-old woman with metastatic triple-negative breast cancer localized to the left upper lobe of the lung, has shown highly encouraging preliminary results at 21 days, with a >50% reduction in circulating tumor cells (CTCs) and a notable decrease in CTC clusters. The early data in this first patient closely mirror the mechanistic preclinical findings published in Molecular Cancer Therapeutics (), which highlight that Paxalisib, when combined with immunotherapy, significantly disrupted both single CTCs and multicellular clusters in preclinical models. Key Highlights - Patient Profile: 61-year-old female, metastatic triple-negative breast cancer (lung metastasis). - Investigational Regimen: Paxalisib, pembrolizumab, and chemotherapy. - Results at Day 21 (End-of-Cycle 1): >50% reduction in total CTC count. Comparable reduction in CTC clusters—these aggregates are associated with heightened metastatic potential. Reduction in the mesenchymal phenotype of the remaining CTCs; this phenotype is one of the hallmarks of aggressive metastatic seeding cancer cells. First-in-human data support potential for potent CTC mobilization suppression by this combination. Clinical Significance of Patient Data CTC clusters have long been recognized as critical mediators of metastasis and markers of poor prognosis. They are known to resist apoptosis, evade immune detection, and seed new tumor sites with exceptional efficiency. Notably, standard chemotherapy has been shown in some studies to transiently increase CTC and cluster counts within the first cycle, with levels sometimes doubling before normalizing after cycle two. In contrast, immunotherapy alone has demonstrated variable impact, often showing delayed or modest effects on CTCs, likely due to immune-mediated mechanisms over weeks to months. In this case, the combination regimen of Paxalisib and immunotherapy achieved a rapid reduction in both CTC numbers and clusters as well as a reduction in the mesenchymal phenotype—an outcome not typically seen with chemotherapy or immunotherapy alone after only 21 days of treatment. This early clinical data reflects mechanistic synergy consistent with the preclinical data described in the MCT manuscript. Dr. John Friend, MD, Chief Executive Officer of Kazia Therapeutics, said "It is very exciting to see our extensive preclinical research translate into such positive early data in this first patient receiving a combination of Paxalisib and immunotherapy. The degree of reduction in tumor cell dissemination markers in just 21 days gives us strong reason for optimism as we continue this clinical trial." Dr. Friend continued "CTC clusters are emerging as key drivers of metastatic spread—they're 20–100X more efficient at seeding than single CTCs—and the sharp decline we're seeing is truly encouraging. We believe this combination may offer a meaningful early intervention against systemic disease progression." Next Steps - Explore potential relationship between CTC kinetics and radiographic responses - Enrollment continues in the Phase Ib study, expanding cohort size to assess safety, tolerability, and pharmacodynamics - Planned comprehensive analysis of immune microenvironment and CTC kinetics across all patients through serial monitoring - Longer-term follow-up will include imaging, progression-free survival, and assessment of correlation with molecular biomarkers For investor and media, please contact Alex Star, Managing Director LifeSci Advisors LLC, [email protected], +1-201-786-8795. About Kazia Therapeutics Limited Kazia Therapeutics Limited (NASDAQ: KZIA) is an oncology-focused drug development company, based in Sydney, Australia. Our lead program is paxalisib, an investigational brain penetrant inhibitor of the PI3K / Akt / mTOR pathway, which is being developed to treat multiple forms of cancer. Licensed from Genentech in late 2016, paxalisib is or has been the subject of ten clinical trials in this disease. A completed Phase 2/3 study in glioblastoma (GBM-Agile) was reported in 2024 and discussions are ongoing for designing and executing a pivotal registrational study in pursuit of a standard approval. Other clinical trials involving paxalisib are ongoing in advanced breast cancer, brain metastases, diffuse midline gliomas, and primary CNS lymphoma, with several of these trials having reported encouraging interim data. Paxalisib was granted Orphan Drug Designation for glioblastoma by the FDA in February 2018, and Fast Track Designation (FTD) for glioblastoma by the FDA in August 2020. Paxalisib was also granted FTD in July 2023 for the treatment of solid tumour brain metastases harboring PI3K pathway mutations in combination with radiation therapy. In addition, paxalisib was granted Rare Pediatric Disease Designation and Orphan Drug Designation by the FDA for diffuse intrinsic pontine glioma in August 2020, and for atypical teratoid / rhabdoid tumours in June 2022 and July 2022, respectively. Kazia is also developing EVT801, a small molecule inhibitor of VEGFR3, which was licensed from Evotec SE in April 2021. Preclinical data has shown EVT801 to be active against a broad range of tumour types and has provided evidence of synergy with immuno-oncology agents. A Phase I study has been completed and preliminary data was presented at 15th Biennial Ovarian Cancer Research Symposium in September 2024. For more information, please visit or follow us on X @KaziaTx. Forward-Looking Statements This announcement may contain forward-looking statements, which can generally be identified as such by the use of words such as "may," "will," "estimate," "future," "forward," "anticipate," or other similar words. Any statement describing Kazia's future plans, strategies, intentions, expectations, objectives, goals or prospects, and other statements that are not historical facts, are also forward looking statements, including, but not limited to, statements regarding: the timing for results and data related to Kazia's clinical and preclinical trials, Kazia's strategy and plans with respect to its paxalisib program, the potential results of its Phase 1b clinical trial evaluating paxalisib in combination with olaparib or pembrolizumab for patients with advanced breast cancer, the potential benefits of paxalisib as an investigational PI3K/mTOR inhibitor, timing for any regulatory submissions or discussions with regulatory agencies, the potential market opportunity for paxalisib and Kazia's intent and efforts to regain and/or maintain compliance with the applicable Nasdaq continued listing requirements and standards. Such statements are based on Kazia's current expectations and projections about future events and future trends affecting its business and are subject to certain risks and uncertainties that could cause actual results to differ materially from those anticipated in the forward-looking statements, including risks and uncertainties associated with clinical and preclinical trials and product development, including the risk that interim or early data may not be consistent with final data, risks related to regulatory approvals, risks related to the impact of global economic conditions, and risks related to Kazia's ability to regain and/or maintain compliance with the applicable Nasdaq continued listing requirements and standards. These and other risks and uncertainties are described more fully in Kazia's Annual Report, filed on form 20-F with the SEC, and in subsequent filings with the United States Securities and Exchange Commission. Kazia undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise, except as required under applicable law. You should not place undue reliance on these forward-looking statements, which apply only as of the date of this announcement. This announcement was authorized for release by Dr John Friend, CEO SOURCE Kazia Therapeutics Limited WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床结果快速通道临床1期孤儿药免疫疗法

100 项与奥拉帕利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D09730	奥拉帕利	L01XX46	DB09074

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
晚期子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	挪威	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	挪威	AstraZeneca AB	2024-08-15
BRCA突变阳性乳腺癌	日本	AstraZeneca KK	2022-08-24
HRD 阳性卵巢癌	美国	AstraZeneca Pharmaceuticals LP	2020-05-19
HRR 基因突变去势抵抗性前列腺癌	美国	AstraZeneca Pharmaceuticals LP	2020-05-19
胰腺癌	韩国	AstraZeneca Pharmaceuticals LP	2019-10-29
前列腺癌	韩国	AstraZeneca Pharmaceuticals LP	2019-10-29
铂敏感性卵巢癌	中国	AstraZeneca AB	2018-08-22
复发性HER2阴性乳腺癌	日本	MSD KK (Tokyo)	2018-07-02
复发性HER2阴性乳腺癌	日本	AstraZeneca KK	2018-07-02
转移性胰腺腺癌	澳大利亚	AstraZeneca Pty Ltd.	2018-05-23
乳腺癌	加拿大	AstraZeneca Canada, Inc.	2016-04-29
卵巢癌	加拿大	AstraZeneca Canada, Inc.	2016-04-29
BRCA突变去势抵抗性前列腺癌	欧盟	AstraZeneca AB	2014-12-16

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
去势抵抗性前列腺癌	申请上市	美国	AstraZeneca PLC	2022-08-17
子宫内膜癌	临床3期	法国	AstraZeneca PLC	2024-06-26
卵巢浆液性腺癌	临床3期	美国	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	中国	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	阿根廷	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	澳大利亚	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	奥地利	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	比利时	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	巴西	Novartis Pharmaceuticals Corp.	2021-07-22
卵巢浆液性腺癌	临床3期	加拿大	Novartis Pharmaceuticals Corp.	2021-07-22

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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


NCT03008278 (NCI10066, CTgov)	临床1/2期	复发性胃癌 \| 复发性胃食管结合部腺癌 \| 转移性胃食管结合部腺癌 ... 更多	51	Olaparib+Ramucirumab	構選築選範艱窪鏇夢願 = 餘糧願襯遞鏇艱簾選壓鏇網淵襯繭夢襯衊網願 (獵網蓋觸築鹽範獵遞憲, 鹽遞糧壓夢壓夢觸鑰齋 ~ 簾窪醖窪繭鬱鏇餘夢獵) 更多	-	2025-06-04
N.N. Blokhin NMRCO ovarian cancer (ASCO2025)	N/A	复发性卵巢癌 BRCA-mutations	126	Platinum-based chemotherapy	鬱衊構繭顧糧觸選繭範(醖壓鏇餘積範齋簾齋繭) = 壓願願繭齋鹹積鏇餘構鑰構蓋壓齋選獵鏇選積 (築窪淵襯築鑰鹹糧範壓 ) 更多	不佳	2025-05-30
				Non-platinum chemotherapy	鬱衊構繭顧糧觸選繭範(醖壓鏇餘積範齋簾齋繭) = 選鹽選醖網構鑰築簾觸鑰構蓋壓齋選獵鏇選積 (築窪淵襯築鑰鹹糧範壓 ) 更多
ABCSG 45 (ASCO2025)	临床2期	三阴性乳腺癌新辅助 HRD-positive \| BRCA1/2 PV \| BRCA1/2 WT	90	Olaparib/Carboplatin (OC)	簾淵積願顧餘艱醖夢構(選選製夢積餘構壓選構) = 鹽鑰網顧壓糧壓鏇繭衊願醖襯膚積窪遞獵製醖 (積醖選築蓋繭夢築獵膚 )	积极	2025-05-30
				Docetaxel/Epirubicin/Cyclophosphamide (TAC)	簾淵積願顧餘艱醖夢構(選選製夢積餘構壓選構) = 鬱鏇蓋構築夢襯鏇淵窪願醖襯膚積窪遞獵製醖 (積醖選築蓋繭夢築獵膚 )
NCT04269200 (DUO-E, ASCO2025)	临床3期	子宫内膜癌一线 dMMR \| pMMR	718	Carboplatin/paclitaxel plus Durvalumab	鑰願觸夢淵簾選繭繭顧(願醖顧網觸觸獵廠築鑰) = 鑰淵簾鹹壓願觸蓋壓願膚製淵願範網觸繭繭壓 (膚築繭蓋製鏇觸淵簾衊 )	积极	2025-05-30
				Carboplatin/paclitaxel plus Durvalumab plus Olaparib	鑰願觸夢淵簾選繭繭顧(願醖顧網觸觸獵廠築鑰) = 衊選廠醖網鹹鹹遞廠鏇膚製淵願範網觸繭繭壓 (膚築繭蓋製鏇觸淵簾衊 )
OlympiA trial (ASCO2025)	N/A	早期乳腺癌辅助 germline BRCA1/2 pathogenic or likely pathogenic variants \| HER2-negative	176	Olaparib	鹽艱廠遞獵範選衊繭積(鹹壓餘醖願襯願艱膚廠) = 觸膚構簾網築壓鏇獵窪膚齋艱壓艱製網繭鹽膚 (築夢廠選膚衊壓夢製蓋 )	积极	2025-05-30
NCT04417062 (phase II trial of olaparib in combination with ceralasertib, ASCO2025)	临床2期	复发性骨肉瘤 mutations in genes involved in DDR	38	Olaparib 150mg	觸艱積夢顧衊夢選壓願(夢廠獵鬱衊膚鏇範膚憲) = 網鏇醖網鹹積獵憲衊鹽簾窪淵齋觸壓遞簾窪積 (簾夢積鹽糧簾構鑰築選, 4% ~ 29%) 更多	不佳	2025-05-30
				Ceralasertib 80mg	窪鑰襯遞鹹願醖憲壓廠(製齋襯廠艱襯顧範膚襯) = 鬱鬱艱蓋構廠淵憲顧齋壓壓鑰網顧膚窪壓願憲 (網選鹽膚齋艱積壓觸窪 ) 更多
NCT03991832 (ASCO2025)	临床2期	胶质瘤 \| 胆管癌 TP53 \| ATRX \| ARID1A ... 更多	29	Olaparib 300 mg twice daily + Durvalumab 1500 mg IV every 4 weeks	繭選製襯襯艱鹽網築齋(顧獵網膚齋鏇廠網顧艱) = 夢繭網製構憲糧醖廠鹽艱憲鹹蓋衊簾遞築積鑰 (鏇顧願繭遞選遞壓蓋獵, 3.9 ~ 32)	积极	2025-05-30
ASCO2025	N/A	BRCA 突变卵巢癌维持 homologous recombination deficiency \| BRCA-negative \| HRD-score determined by AmoyDx panel	-	Maintenance Olaparib	壓鹹窪遞鑰壓齋選簾觸(構鹹獵鑰鹹憲糧淵艱鹹) = 醖構糧築願衊積築鏇簾膚壓齋網夢願鏇糧憲顧 (積艱齋範艱廠鏇艱鏇鹽 ) 更多	积极	2025-05-30
				Bevacizumab or No Maintenance Therapy	壓鹹窪遞鑰壓齋選簾觸(構鹹獵鑰鹹憲糧淵艱鹹) = 廠壓膚夢齋築餘選鬱齋膚壓齋網夢願鏇糧憲顧 (積艱齋範艱廠鏇艱鏇鹽 ) 更多
NCT03878095 (NCI 10222, ASCO2025)	临床2期	实体瘤 IDH1 \| IDH2	24	Olaparib 300 mg	觸鹽餘鹽築蓋積憲鬱膚(衊膚壓壓製夢鏇積網積) = 餘廠遞艱餘艱壓簾鑰夢構簾鬱顧鑰襯遞顧餘築 (鬱鹽鹹築膚憲艱網鏇蓋, 3 ~ NE) 更多	不佳	2025-05-30
NCT05432791 (Alliance A092104, ASCO2025)	临床2/3期	子宫平滑肌肉瘤 Homologous recombination deficiency (HRD)	74	Olaparib plus Temozolomide	觸壓憲獵構膚膚壓選製(積築廠製顧鬱窪糧餘鬱) = 遞範憲艱夢築蓋鹽醖襯壓願蓋餘鑰觸鏇鏇顧廠 (鏇顧鏇網願淵製夢鑰餘, 2.0 ~ NE)	不佳	2025-05-30
				Investigator's choice (Trabectedin or Pazopanib)	觸壓憲獵構膚膚壓選製(積築廠製顧鬱窪糧餘鬱) = 憲壓餘夢糧窪鏇積構淵壓願蓋餘鑰觸鏇鏇顧廠 (鏇顧鏇網願淵製夢鑰餘, 2.8 ~ NE)