An Open-label, Dose-escalation, and Dose-expansion Phase I/II Clinical Study of Safety, Tolerability, Pharmacokinetic Profile, and Initial Efficacy of LM-2417 for Injection Alone or in Combination With Other Antitumor Agents in Patients With Advanced Solid Tumors

This study is to assess the safety and tolerability, obtain the recommended phase 2 dose(RP2D)/or Maximum Tolerated Dose (MTD) for LM-2417 as a single agent or in combination with other anti-tumour agents in subjects with advanced solid tumours.

开始日期2025-06-05

申办/合作机构

礼新医药科技（上海）有限公司

NCT06412120

/ Suspended临床4期IIT

Single-Arm, Prospective, Multicenter Study Evaluating Safety, Tolerability, and Metabolism of Niraparib as Maintenance Following Front-Line Treatment for Ovarian Cancer in Women of African Ancestry

The purpose of this study is to identify the genetic characteristic(s), specifically degree of African ancestry, and environmental characteristic(s) that appear to be related to the effects, both good and bad, that the maintenance treatment has women with ovarian cancer. In this study, an investigational medication called niraparib is being tested for the treatment of ovarian cancer. Niraparib works by blocking the ability of cancer cells to fix their genes. Cancer cells with damaged genes have a harder time growing and spreading in the body and can even die.

开始日期2025-06-01

申办/合作机构

University of Miami

[+1]

CTRI/2025/04/085112

/ Not yet recruiting临床4期

A Prospective, Multicentre, open labelled, single arm Phase IV Clinical Trial of Niraparib in Indian Patients with advanced or relapsed Ovarian Cancer who are in Complete or Partial Response Following Platinum based Chemotherapy. - NIL

开始日期2025-05-20

申办/合作机构-

100 项与甲苯磺酸尼拉帕利相关的临床结果

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100 项与甲苯磺酸尼拉帕利相关的转化医学

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100 项与甲苯磺酸尼拉帕利相关的专利（医药）

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1,023

项与甲苯磺酸尼拉帕利相关的文献（医药）

2025-11-01·TALANTA

Advanced sensor technologies for niraparib detection: A comparative study of molecularly imprinted polymer and nanosensor systems

Article

作者: Ozkan, Sibel A ; Samanci, Seyda Nur ; Ozcelikay-Akyildiz, Goksu ; Bellur Atici, Esen

Poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) inhibitors are crucial for maintenance therapy in ovarian cancer patients with BRCA mutations, with niraparib (NRB) being a significant example in this class of drugs. This study focuses on developing and comparing two distinct sensor technologies, a molecularly imprinted polymer (MIP)-based sensor and a nanosensor, for the sensitive and selective detection of NRB. The MIP-based electrochemical sensor was constructed using electropolymerization in the presence of aniline (ANI), 3-aminophenyl boronic acid (3-APBA), and NRB as the template molecule. Conversely, the nanosensor incorporated zinc oxide (ZnO) and gold nanoparticles (AuNPs) to enhance signal detection. The sensors were characterized using scanning electron microscopy (SEM) to ensure structural integrity and material composition. The performance of both sensors was optimized, and their analytical capabilities were assessed and compared. The MIP-based sensor demonstrated a concentration range of 2-10 pM with a detection limit (LOD) of 0.408 pM, as measured by differential pulse voltammetry (DPV). The nanosensor, optimized using adsorptive stripping differential pulse voltammetry (AdSDPV), displayed a broader concentration range of 80-600 nM and a LOD of 0.893 nM. This comparison revealed that the MIP-based sensor had superior sensitivity for NRB detection. Both sensors were successfully applied to the analysis of commercial human serum samples, showing excellent repeatability (n = 5) with a relative standard deviation (RSD) below 2.0 %. Recovery rates were highly satisfactory, ranging from 98.83 % to 101.33 %. These findings underscore the effectiveness of both sensors for precise, selective, and sensitive NRB detection, with the MIP-based sensor offering heightened sensitivity.

2025-08-01·NEOPLASIA

Alteration in expression and subcellular localization of the androgen receptor- regulated FAM111A protease is associated with emergence of castration resistant prostate cancer

Article

作者: Siddiqui, Salma ; Durbin-Johnson, Blythe P ; Tsamouri, Maria Malvina ; Luo, Jun ; Ghosh, Paramita M ; Mudryj, Maria ; Jathal, Maitreyee K ; Libertini, Stephen J ; Corey, Eva ; Tepper, Clifford G ; Iczkowski, Kenneth A

The androgen receptor (AR) is a pivotal regulator of growth and survival of prostate cancer (PCa) and the majority of lethal castration-resistant prostate cancers (CRPC) remain reliant on AR signaling. PCa exhibits variability in progression and responses to treatment suggesting genetic heterogeneity. Two independent studies identified PCa predisposing single nucleotide polymorphisms (SNPs) within the FAM111A protease gene, but the mechanistic basis of this association remained elusive. Our in vitro and in vivo studies uncovered that AR represses FAM111A in castration sensitive and resistant cells via an AR binding site within the FAM111A gene. FAM111A levels are significantly lower in matched castration-resistant than in castration-sensitive cells and xenografts, and lower in metastatic lesions than in primary tumors. We discovered that FAM111A is AR-repressed in castration sensitive PCa xenograft and multiple PCa cells. Additionally, FAM111A subcellular localization changes dramatically with acquisition of castration resistance, where in castration sensitive cells FAM111A is predominantly in the nucleoli, but with castration resistance it becomes more dispersed in the nucleus and in the cytoplasm. FAM111A depletion in castration sensitive and resistant cells enhances the efficacy of PARP1 inhibitors olaparib and niraparib, consistent with its role in DNA repair. Moreover, FAM111A depletion reduces AR target gene prostate specific antigen (PSA) and transmembrane serine protease 2 (TMPRSS2) transcription, indicating that FAM111A modulates AR-dependent gene expression forming a FAM111A-AR co-regulatory loop in PCa. Our studies argue that AR-dependent FAM111A regulation modulates PCa gene expression, acquisition of castration resistance, and sensitivity to agents that target DNA damage repair.

2025-07-01·JOURNAL OF CONTROLLED RELEASE

Radiation-guided nanoparticles enhance the efficacy of PARP inhibitors in primary and metastatic BRCA1-deficient tumors via immunotherapy

Article

作者: Longobardi, Giuseppe ; Guedes, Rita C ; Yona, Adi ; Venkert, Dana ; Khoury, Rami ; García Alvarado, América ; Green Buzhor, Marina ; Zhao, Jean J ; Florindo, Helena F ; Acúrcio, Rita C ; Satchi-Fainaro, Ronit ; Wang, Qiwei ; Barnatan, Tania T ; Shahar, Shir

Poly (ADP-ribose) polymerase inhibitors (PARPi) have revolutionized the treatment landscape for patients suffering from BRCA1-mutated breast and ovarian cancers. However, responses are not durable. We demonstrate that treatment with PARPi, niraparib, increases programmed death-ligand 1 (PD-L1) expression in BRCA1-deficient cancer cells, contributing to immune evasion. To circumvent this, we developed P-selectin-targeted poly (lactic-co-glycolic) acid (PLGA)-poly (ethylene glycol) (PEG)-based nanoparticles (NPs) encapsulating PARP and PD-L1 inhibitors at a synergistic ratio. To further enhance tumor targeting, we leveraged radiation-induced P-selectin upregulation in BRCA1-deficient cancer cells and their associated angiogenic endothelial cells, improving NP accumulation in the primary tumors and hard-to-target metastatic sites, including brain metastasis. Using a combination of traditional 2-dimensional (2D) cell cultures, advanced 3-dimensional (3D) spheroids, tumor-on-a-chip platforms, and in vivo models, we demonstrate the enhanced accumulation and efficacy of the radiation-guided P-selectin-targeted NPs in primary and brain-metastatic BRCA1-deficient tumors.

651

项与甲苯磺酸尼拉帕利相关的新闻（医药）

2025-06-04

·奇点网

程颖教授解读ES-SCLC维持治疗，IMforte点亮生命新曙光

*仅供医学专业人士阅读参考在近日的2025年美国临床肿瘤学会（ASCO）年会上，全球性III期关键临床研究IMforte结果重磅发布，并同步以论文形式登上《柳叶刀》，带来了ES-SCLC一线维持治疗的全新选择：对阿替利珠单抗联合化疗一线治疗后未发生疾病进展的患者，阿替利珠单抗+芦比替定双药维持治疗，对比阿替利珠单抗单药维持治疗，取得了双主要终点-独立评审无进展生存期（PFS）和总生存期（OS）双阳性结果。这是在ES-SCLC领域首个维持治疗取得阳性结果的全球III期研究，是ES-SCLC治疗历程上又一项里程碑式的研究！程颖教授吉林省肿瘤医院一级教授，博士研究生导师，博士后工作站导师享受国务院特殊津贴，卫生部突出贡献中青年专家吉林省肿瘤医院恶性肿瘤临床研究一体化诊疗中心主任吉林省癌症中心主任吉林省肺癌诊疗中心主任中国临床肿瘤学会（CSCO) 监事会副监事长北京希思科临床肿瘤学研究基金会副理事长国际肺癌研究协会（IASLC）罕见肿瘤（小细胞肺癌）专委会委员中国抗癌协会小细胞肺癌专委会主任委员CSCO临床研究专家委员会主任委员CSCO小细胞肺癌专家委员会前任主任委员CSCO非小细胞肺癌专家委员会副主任委员中华医学会肿瘤学分会肺癌专委会副主任委员中国医师协会肿瘤多学科诊疗专委会副主任委员2023、2024年度临床医学领域“全球高被引科学家”建立维持治疗新标准，引领ES-SCLC治疗持续向前IMforte研究是一项全球、多中心、随机对照III期关键临床试验，共纳入660例ES-SCLC患者，一线给予阿替利珠单抗+化疗诱导治疗4个周期，此后对疾病无进展的483例患者按1:1比例，随机至阿替利珠单抗+芦比替定维持治疗组或阿替利珠单抗单药维持治疗组，治疗至疾病进展或发生不可耐受的毒性，本研究不允许组间交叉（Crossover）。值得注意的是，IMforte研究采用开放标签设计，且未纳入存在中枢神经系统（CNS）转移的ES-SCLC患者，这两点都与芦比替定有关，一方面是因为它的不良反应，如胃肠道和血液学不良事件及处理策略（如使用止吐药、G-CSF等）较易被医生和患者识别，另一方面则是在IMforte研究启动时，芦比替定对存在CNS转移灶患者的临床获益尚不明确。IMforte研究主要疗效终点为独立评审机构（IRF）评估的患者PFS和OS，次要终点则为研究者评估的PFS，客观缓解率（ORR）、缓解持续时间（DoR）等，各项疗效数据均从维持治疗启动时开始评估。IMforte研究设计在本届ASCO年会上，IMforte研究的主要结果以口头报告形式正式公布：阿替利珠单抗+芦比替定维持治疗组患者的mPFS为5.4个月，显著优于对照组的2.1个月，联合方案维持治疗使患者疾病进展或死亡风险显著下降了46%（HR=0.54, P<0.0001），且各预设亚组获益整体一致；两组mOS则分别为13.2个月和10.6个月，联合方案维持治疗使患者死亡风险相对下降27%（HR=0.73, P=0.0174），关键预设亚组中观察到一致的生存获益。IMforte研究PFS、OS数据安全性数据显示，在阿替利珠单抗+芦比替定维持治疗组患者中位治疗时长达到4.1个月，近乎对照组两倍（2.1个月）的前提下，联合方案维持治疗组发生的大多数不良事件，尤其是血液学不良事件仍程度较轻，多数仅为1-2级，提示研究要求的G-CSF预处理策略，可有效应对芦比替定治疗相关血液学毒性；虽然联合方案组的3-4级治疗相关不良事件（TRAEs）发生率稍高，但整体永久停药率仍较低，反映不良事件大多可管可控。IMforte研究安全性数据IMforte研究PFS和OS双主要终点阳性，实现有统计学意义和临床意义的显著改善，再加上治疗安全性良好，交出的无疑是一份高分答卷，阿替利珠单抗+芦比替定方案也即将由此确立一线维持治疗新标准的地位。专家点评如何提高ES-SCLC患者的生存一直是临床不断攻坚探索的难题，尽管ES-SCLC初始治疗有效率较高，但大部分患者在诱导治疗结束后快速复发，疾病复发后进展迅速，预后极差。如何改善ES-SCLC的生存，有效的维持治疗被认为是巩固一线治疗成果，延长无进展生存时间，进而提高总生存期的重要策略。多年来，ES-SCLC的维持治疗策略不断在进行探索，在经历了非常艰难和曲折的历程后，今年终于迎来了曙光。一、ES-SCLC维持治疗的前世：在困境中的探索在含铂双药化疗作为ES-SCLC标准一线治疗方案时代，针对如何寻找适合的维持治疗策略进行了多样的探索，这时的策略是在诱导化疗结束后，对于疾病未进展的患者探寻有效的维持治疗药物，但是多年来研究进展一直举步维艰。在探索维持治疗的早期阶段，因为SCLC缺乏更多的抗肿瘤药物，对标准EC或EP方案化疗后，维持治疗的探索主要是给予不同化疗药物，几项研究应用口服依托泊苷胶囊维持治疗或者给予拓扑替康等化疗药物维持治疗，但均没有获得生存获益。此后，针对抗血管生成药物在维持治疗阶段的疗效进行了评估，但是无论是大分子的贝伐珠单抗，还是小分子抗血管抑制剂帕唑帕尼等几项II期研究均未达到主要终点。随后，靶向药物、ADC和免疫药物也进行了维持治疗的探索。在PARP抑制剂方面，应用尼拉帕利维持治疗的III期研究结果显示仅有轻微的PFS获益，但OS没有获益；在早期靶向DLL3的ADC药物方面，MERU这项III期研究应用Rova-T进行维持治疗，由于该药物的毒性维持治疗也没有显示出OS获益，并停止在SCLC的研发；进入免疫治疗时代，CheckMate-451研究作为免疫治疗领域第一个，在标准化疗4周期结束后，免疫维持治疗的III期研究，结果显示纳武利尤单抗单药或者纳武利尤单抗联合伊匹木单抗作为维持治疗，两组都没有带来OS获益。因此，无论是化疗、抗血管生成治疗、PARP抑制剂、ADC药物还是免疫治疗，一线采用标准化疗结束后给予维持治疗均纷纷折戟，维持治疗在ES-SCLC一度停滞不前。二、ES-SCLC维持治疗的今生：拨开迷雾见曙光近年来，免疫联合化疗一线治疗ES-SCLC实现了里程碑式的跨越，目前免疫联合化疗诱导治疗4~6个周期后，给予免疫单药维持治疗成为标准治疗策略。在IMpower133研究的探索性分析中发现，自维持治疗开始阿替利珠单抗组的中位OS和PFS分别为12.5个月和2.6个月，均高于安慰剂对照组的8.4个月和1.8个月，死亡风险和疾病进展风险得到进一步下降（HR为0.59和0.63），意味着在一线ES-SCLC免疫联合化疗带来的生存获益基础上，继续免疫维持治疗同样有着重要贡献。因此，ES-SCLC一线化疗联合免疫治疗后，维持治疗是提高患者生存的重要探索方向。如何能够进一步提高维持治疗的疗效，以及针对SCLC冷肿瘤的微环境特点，多种以免疫为基础的联合治疗策略进行了探索。在免疫联合化疗维持治疗方面，此次ASCO年会上报告的IMforte研究采用阿替利珠单抗联合芦比替定维持治疗。芦比替定已获批ES-SCLC二线治疗适应证，从作用机制上看，芦比替定不仅有抑制癌基因转录、诱导癌细胞凋亡的主要功能，还在临床前研究中展现了通过减少巨噬细胞数量、抑制肿瘤新生血管形成、诱导癌细胞免疫原性死亡等方式，正向调节肿瘤微环境的作用。在临床研究方面，I期数据表明阿替利珠单抗联合芦比替定作为ES-SCLC二线治疗的ORR为58%，患者中位PFS达到4.93个月，提示该联合方案具有较好的抗肿瘤活性。IMforte研究也是首个在ES-SCLC维持治疗阶段，成功取得PFS和OS双阳性结果的III期研究，实现了在IMpower133研究基础上进一步延长患者生存的目标，在ES-SCLC维持治疗领域具有开创性的意义。在免疫联合抗血管维持治疗方面，DURABLE研究是一项度伐利尤单抗联合安罗替尼对比度伐利尤单抗维持治疗的II期研究，研究显示从诱导治疗开始，度伐利尤单抗联合安罗替尼维持治疗和度伐利尤单抗单药维持治疗组的PFS分别为9.0个月和5.6个月，OS分别为20.4个月和15.4个月，这项研究提示免疫联合多靶点抗血管药物维持治疗是具有前景的研究方向。此外，我们牵头进行的ETER701研究，在诱导化疗开始时给予安罗替尼联合贝莫苏拜单抗四药联合治疗，然后给予安罗替尼联合贝莫苏拜单抗维持治疗，PFS和OS分别6.9个月和19.3个月，PFS和OS数据均得到显著延长，OS延长7.4个月显著优于既往免疫联合化疗一线治疗的历史数据，结果进一步支持免疫联合抗血管维持治疗具有很好的疗效和安全性。在免疫联合DLL3/CD3双抗维持治疗方面，DeLLphi-303 研究是一项塔拉妥单抗联合PD-L1抑制剂维持治疗ES-SCLC的1b期研究，塔拉妥单抗联合PD-L1抑制剂维持治疗的 PFS 为 5.6 个月，安全性良好，为正在进行的塔拉妥单抗联合度伐利尤单抗维持治疗的III期研究DeLLphi-305研究提供了支持，该研究也可能成为SCLC免疫维持治疗的下一个突破口。在免疫联合PARP抑制剂维持治疗方面，SWOG S1929研究是一项评估阿替利珠单抗联合他拉唑帕利对比阿替利珠单抗维持治疗的II期研究，纳入一线阿替利珠单抗联合化疗治疗未进展且SLFN11阳性ES-SCLC患者，结果显示SLFN11阳性患者联合维持治疗PFS有一定获益趋势；一项I期研究评估奥拉帕利联合度伐利尤单抗维持治疗的疗效和安全性正在进行中，未来仍有待进一步的结果公布。此外，在免疫联合放疗维持治疗方面，一项II期研究在ES-SCLC患者接受阿得贝利单抗联合化疗4~6个周期诱导治疗后，对产生应答的患者给予阿得贝利单抗联合胸部巩固放疗，后续再给予阿得贝利单抗维持治疗。结果显示，中位PFS为10.1个月，中位OS为21.4个月，接受和未接受胸部放疗患者的中位OS分别为22.9个月和13.4个月，与仅接受免疫单药维持治疗的历史数据相比，免疫联合放疗巩固维持治疗的模式患者生存数据有一定提高，但仍需III期研究的进一步验证。三、ES-SCLC维持治疗的未来：探索分子分型和生物标记物指导的治疗在ES-SCLC维持治疗策略中，以生物标记物或分子分型指导的维持治疗策略将是重要的探索方向。目前，尚没有生物标志物来指导SCLC维持治疗的治疗决策。近年来，一些研究对SCLC免疫治疗的生物标志物进行了探索，研究结果显示RB1突变状态、MYC表达、肿瘤浸润淋巴细胞、表观遗传异常和肿瘤新抗原等生物标记物可能是SCLC免疫治疗潜在生物标志物。在一项临床前的研究中，研究者发现SLFN11高表达的细胞系对芦比替定更敏感，SLFN11低表达鼠模型对芦比替定的敏感性明显较低，SLFN11可能预测对芦比替定的敏感性。这些生物标记物在SCLC的应用还有很长的路要走，仍需要更多前瞻性研究进一步的验证。基于分子分型的研究可能为SCLC免疫治疗带来了新的方向。根据关键转录因子的表达，SCLC可分为不同的转录亚型，如SCLC - A、SCLC - N、SCLC - P和SCLC - Y/I等。不同亚型具有不同的生物学特性和治疗敏感性，SCLC - Y/I亚型免疫细胞浸润和检查点分子表达较高，患者的OS有延长趋势；SCLC-P亚型则与较差的预后相关。在免疫联合治疗策略中，SCLC-Y/I亚型显示出预测疗效的潜力；SCLC-A和SCLC-N亚型中DLL3表达较高，可能与对Tarlatamab的治疗应答有关。但转录亚型在预测 ICI 单药治疗效果时存在局限性，多组学整合研究有助于更全面地了解SCLC的生物学特性，分子分型作为免疫治疗生物标志物的可靠性还需更多前瞻性临床研究验证。四、总结芦比替定联合阿替利珠单抗维持治疗的成功标志着ES-SCLC治疗迈出重要一步，新兴治疗策略的发展为SCLC维持治疗提供了新的机遇，随着更多创新型药物在SCLC领域的不断探索以及研究结果的公布，将为ES-SCLC一线维持治疗提供更多治疗选择，未来维持治疗的格局可能进一步多元化。如何筛选维持治疗的获益人群，优化维持治疗的联合策略仍然充满着挑战，随着对SCLC生物学的深入了解和生物标记物的研发，未来有望为SCLC患者带来新的希望。参考文献：[1]Rudin C M, Liu S V, Soo R A, et al. SKYSCRAPER-02: tiragolumab in combination with atezolizumab plus chemotherapy in untreated extensive-stage small-cell lung cancer[J]. Journal of Clinical Oncology, 2024, 42(3): 324-335.[2]Ohe Y, Han B, Nishio M, et al. BEAT-SC: A randomized phase III study of bevacizumab or placebo in combination with atezolizumab and platinum-based chemotherapy in patients with extensive-stage small cell lung cancer (ES-SCLC)[J]. Journal of Clinical Oncology, 2024, 42(16_suppl): 8001.[3]Reck M, Dziadziuszko R, Sugawara S, et al. Five-year survival in patients with extensive-stage small cell lung cancer treated with atezolizumab in the Phase III IMpower133 study and the Phase III IMbrella A extension study[J]. Lung Cancer, 2024, 196: 107924.[4]Kao S C H, Reck M, Liu S V, et al. 634P Whole exome sequencing (WES) analyses from IMpower133 and 6-year (y) overall survival (OS) from IMbrella A in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC) treated with atezolizumab (atezo)[J]. Annals of Oncology, 2024, 35: S1638.[5]Reck M, Mok T S K, Mansfield A, et al. Brief report: exploratory analysis of maintenance therapy in patients with extensive-stage SCLC treated first line with atezolizumab plus carboplatin and etoposide[J]. Journal of Thoracic Oncology, 2022, 17(9): 1122-1129.[6]Zhang S, Cheng Y. Immunotherapy for extensive-stage small-cell lung cancer: current landscape and future perspectives[J]. Frontiers in Oncology, 2023, 13: 1142081.[7]Aix S P, Navarro A, Bernabe R, et al. 464 2SMALL (NCT04253145) phase I part: lurbinectidine (LUR) in combination with atezolizumab (ATZ) for second line extensive stage small cell lung cancer (ES-SCLC) patients (pts)[J]. Journal for Immunotherapy of Cancer, 2021, 9(Suppl 2): A493.

ASCO会议临床3期临床结果CSCO会议

2025-06-03

·药明康德

首个！癌症进展风险减半，强生小分子组合疗法3期结果亮眼

强生（Johnson & Johnson）公司今日公布其3期AMPLITUDE研究的首次结果。该研究评估其PARP抑制剂niraparib联合醋酸阿比特龙和泼尼松（AAP）在携带同源重组修复（HRR）基因突变（包括BRCA）的转移性去势敏感性前列腺癌（mCSPC）患者中的疗效。结果显示，该联合方案在影像学无进展生存期（rPFS）和发生症状进展时间（TSP）方面均获得临床意义显著且具有统计学意义的改善，并初步显示出总生存期（OS）改善的趋势，凸显了该治疗组合在延缓疾病进展及症状恶化方面的潜力。根据新闻稿，这是在mCSPC患者中，PARP抑制剂联合治疗展现出临床改善效果的首个3期研究。AMPLITUDE是一项进行中的国际多中心、随机双盲、安慰剂对照3期研究，旨在评估Akeega（niraparib与醋酸阿比特龙的双机制复合片[DAT]）联合泼尼松和雄激素剥夺治疗（ADT）的疗效与安全性。对照组为匹配安慰剂/醋酸阿比特龙联合泼尼松与ADT。研究对象为696例携带HRR基因突变的mCSPC患者。研究的主要终点为影像学无进展生存期。分析显示，试验达成rPFS主要终点。在BRCA突变患者（n=191）中，niraparib联合治疗展现出显著的获益，患者的中位rPFS尚未达到，而对照组为26个月，疾病影像学进展或死亡风险降低了48%（HR=0.52；95% CI：0.37-0.72，p<0.0001）。在所有HRR突变患者中，niraparib联合治疗组患者同样未达到中位rPFS，而对照组患者的中位rPFS则为29.5个月，疾病进展或死亡风险降低37%（HR=0.63；95% CI：0.49-0.80，p=0.0001）。此外，在BRCA突变患者中，niraparib联合治疗将症状进展风险降低了56%（HR=0.44；95% CI：0.29-0.68，p=0.0001），在所有HRR突变患者中则降低了50%（HR=0.50；95% CI：0.36-0.69，p<0.0001），意味着患者在症状恶化、需接受放疗、手术或新一轮抗肿瘤治疗前的时间显著延长。图片来源：123RF分析还显示，niraparib联合治疗将BRCA突变患者的死亡风险降低了25%（HR=0.75；95% CI：0.51-1.11，p=0.15），在所有HRR突变患者中则降低了21%（HR=0.79；95% CI：0.59-1.04，p=0.10），显示出niraparib联合治疗的潜在初步总生存获益趋势，目前试验仍在随访中以获得更成熟的数据。安全性方面，3/4级不良事件（AE）在niraparib联合治疗组更为常见（75%对比59%），其中贫血与高血压为最常见不良反应；但因不良事件导致的停药率仍较低（14.7%对比10.3%）。截至目前，niraparib联合醋酸阿比特龙与泼尼松的安全性特征与既往研究一致。图片来源：123RF强生创新药品事业部前列腺癌与免疫治疗领域副总裁Charles Drake博士表示：“AMPLITUDE研究旨在评估患者在癌症尚未进展的阶段能够维持稳定状态的时间。我们发现，niraparib联合醋酸阿比特龙和泼尼松的治疗方案确实实现了这一目标，为患者在疾病进入更具耐药性的阶段前争取了宝贵的高质量的时光。这一突破凸显了对于携带HRR突变，特别是BRCA突变的mCSPC患者，尽早启动个体化治疗策略的重要性。”Niraparib是一种高选择性的PARP口服抑制剂；醋酸阿比特龙则是一种口服给药的雄激素生物合成抑制剂。前列腺癌是全球男性第二大最常确诊的恶性肿瘤，大多数男性在确诊时患有局部前列腺癌，可通过手术或放疗进行治疗。转移性去势敏感性前列腺癌也称为转移性激素敏感性前列腺癌（mHSPC），是指对ADT仍应答但癌细胞已扩散到身体其他部位的前列腺癌。这类患者在经过持续ADT后可能会进展成耐药性癌症。参考资料：[1] Johnson & Johnson leads with first PARP inhibitor combo to improve efficacy in patients with HRR-altered mCSPC. Retrieved June 3, 2025 from https://www.investor.jnj.com/news/news-details/2025/Johnson--Johnson-leads-with-first-PARP-inhibitor-combo-to-improve-efficacy-in-patients-with-HRR-altered-mCSPC/default.aspx免责声明：本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。版权说明：欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床3期临床结果

2025-06-03

·FiercePharma

ASCO: J&J's Akeega gives PARP a novel prostate cancer win, but FDA path in patient subset unclear

In castration-sensitive prostate cancer, the Akeega regimen’s magnitude of progression-free survival benefit was notably bigger at 48% in the BRCA-mutated subgroup when compared with the overall trial population. The FDA has already approved PARP inhibitors in certain patients with metastatic castration-resistant prostate cancer (mCRPC). Now, Johnson & Johnson’s Akeega is giving the class a win in castration-sensitive disease, although the drug’s benefit in a patient subgroup remains unclear.In patients with metastatic castration-sensitive prostate cancer (mCSPC) with homologous recombination repair (HRR), Akeega and prednisone significantly reduced the risk of tumor progression or death by 37% versus J&J’s Zytiga and prednisone, according to data shared at the 2025 American Society of Clinical Oncology annual meeting. Akeega is a fixed-dose combination of GSK’s PARP inhibitor Zejula—to which J&J owns prostate cancer rights—and Zytiga.Despite the positive readout from the phase 3 Amplitude trial, saying Akeega has a clear regulatory path ahead in all HRR-mutated mCSPC would be too optimistic.The uncertainty lies in a group of patients without BRCA mutations.Previously, Zejula’s addition to Zytiga and prednisone showed a progression-free survival benefit in HRR-mutated mCRPC in the phase 3 Magnitude trial. But after speaking with the FDA and realizing that the drug was most beneficial in the BRCA-mutated population, J&J filed for—and received—an approval only in that subset of patients. Now, Amplitude is facing the same BRCA/non-BRCA question. Compared with the entire trial population, the Akeega regimen’s magnitude of progression-free survival benefit was notably bigger at 48% in the BRCA-mutated subgroup.“The benefit may be greatest in patients with BRCA alterations,” lead study author Gerhardt Attard, M.D., Ph.D., from University College London, said during a press briefing.The result is still in favor of Akeega in the non-BRCA subgroup, with an improvement of around 20%, Attard noted.“There is efficacy in the non-BRCA subgroup,” Attard said. “It’s heterogeneous, and it’s a number of different smaller gene subgroups.”“You’re going to need to do meta-analysis of multiple different trials to have certainty which subgroup has clear evidence of efficacy.”The non-BRCA subgroup is not small, accounting for 45% of the Amplitude population. Based on the current data, Akeega doesn’t appear to work in patients with the PALB2 mutation, but there are positive trends in other subtypes, Mark Wildgust, Ph.D., vice president of oncology global medical affairs at J&J Innovative Medicine, said in an interview with Fierce Pharma.“Does it have the same magnitude [of benefit as in BRCA]? I do not believe it does,” Wildgust said. “Is there enough there for regulatory approval? Maybe not right now, but maybe in the future. Maybe we have to wait a bit longer to see longer-term follow up and to understand the question.”J&J will have a discussion with global regulators, including the FDA, on whether the Amplitude trial has shown a positive risk-benefit profile in the overall HRR population, Wildgust said.Besides progression-free survival, researchers also identified a positive trend toward improved overall survival in the Akeega arm. However, data here were immature and didn’t meet statistical significance at the current analysis. The preliminary death reduction was 25% in the BRCA-mutated group and 21% in the overall trial population.Editor's Note: The story was updated to clarify the situation around Akeega's mCRPC indication.

临床结果临床3期ASCO会议

100 项与甲苯磺酸尼拉帕利相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
-	甲苯磺酸尼拉帕利	L01XX54	DB11793

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
BRCA 突变卵巢癌	美国	GlaxoSmithKline LLC	2019-10-23
卵巢癌	瑞士	Tesaro, Inc.	2018-10-03
腹膜癌	瑞士	Tesaro, Inc.	2018-10-03
铂敏感性卵巢上皮癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性卵巢上皮癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性卵巢上皮癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性卵巢上皮癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性输卵管癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性输卵管癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性输卵管癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性输卵管癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性原发性腹膜癌	欧盟	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性原发性腹膜癌	冰岛	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性原发性腹膜癌	列支敦士登	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
铂敏感性原发性腹膜癌	挪威	GlaxoSmithKline (Ireland) Ltd.	2017-11-16
输卵管癌	美国	GlaxoSmithKline LLC	2017-03-27
卵巢上皮癌	美国	GlaxoSmithKline LLC	2017-03-27
原发性腹膜癌	美国	GlaxoSmithKline LLC	2017-03-27

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
BRCA突变去势抵抗性前列腺癌	申请上市	欧盟	GlaxoSmithKline (Ireland) Ltd.	2023-02-27
多形性胶质母细胞瘤	临床3期	美国	GSK Plc	2024-06-19
多形性胶质母细胞瘤	临床3期	法国	GSK Plc	2024-06-19
多形性胶质母细胞瘤	临床3期	荷兰	GSK Plc	2024-06-19
多形性胶质母细胞瘤	临床3期	挪威	GSK Plc	2024-06-19
多形性胶质母细胞瘤	临床3期	西班牙	GSK Plc	2024-06-19
胰腺癌	临床3期	中国	再鼎医药（上海）有限公司	2023-05-30
三阴性乳腺癌	临床3期	美国	GSK Plc	2021-06-28
三阴性乳腺癌	临床3期	日本	GSK Plc	2021-06-28
三阴性乳腺癌	临床3期	阿根廷	GSK Plc	2021-06-28

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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


JPRN-jRCT2031220179 (NiraPim (EPOC2102), ASCO2025)	临床1期	实体瘤 BRCA \| CDK12	30	Niraparib 200 mg + Pimitespib 80 mg	餘鏇醖製遞鹹鑰繭壓觸(願顧簾憲夢遞願淵憲蓋) = 觸醖鹹積艱築顧鏇繭蓋壓糧鑰築壓夢獵觸艱獵 (膚鏇鹹製壓獵繭艱獵鏇 ) 更多	积极	2025-05-30
NCT04734665 (KGOG3056/NIRVANA-R, ASCO2025)	临床2期	维持 BRCA status \| homologous recombination deficiency (HRD) status \| circulating tumor DNA (ctDNA) ... 更多	44	Niraparib rechallenge with bevacizumab	淵淵顧繭選鹹齋觸遞醖(壓選憲艱製廠製遞衊窪) = 遞膚鏇醖醖鹽觸廠簾膚窪齋範壓夢願艱範壓餘 (顧觸選鹽夢齋鏇蓋壓憲, 55 ~ 85)	积极	2025-05-30
JPRN-jRCT2051210120 (IMAGENE, ASCO2025)	临床2期	RET突变实体瘤 HRR gene mutation	47	Niraparib + Nivolumab	構選淵襯夢醖選膚餘築(顧選鬱願鑰網鹽網艱餘) = 齋製繭膚齋廠蓋憲範簾淵繭膚襯鑰衊壓積願鹽 (簾廠繭餘獵製簾夢願顧, 0.8 ~ 13.3) 更多	积极	2025-05-30
JPRN-jRCT2051210120 (IMAGENE, ASCO2025)	临床2期	RET突变实体瘤 HRR gene mutation	47	Placebo	網繭壓構選觸齋積糧築(製範簾獵獵鬱衊鏇艱艱) = 網淵鹽廠艱顧築憲鹽襯鏇衊壓繭醖範鹹窪膚衊 (齋網夢衊鏇齋壓選繭觸, 29.1 ~ 53.8)	积极	2025-05-30
ASCO2025	N/A	卵巢癌	20	Niraparib	網壓鑰醖艱艱製衊憲鬱(積鏇蓋糧餘築艱築膚壓) = 醖選觸製膚衊窪鬱壓願積襯鑰顧醖製襯獵積積 (蓋範艱網遞窪願鹹壓簾 )	-	2025-05-30
ASCO2025	N/A	卵巢癌	20	Placebo	網壓鑰醖艱艱製衊憲鬱(積鏇蓋糧餘築艱築膚壓) = 製襯觸壓鏇壓鏇鬱餘網積襯鑰顧醖製襯獵積積 (蓋範艱網遞窪願鹹壓簾 )	-	2025-05-30
NCT04030559 (ASCO2025)	临床2期	局限性前列腺癌新辅助 BRCA2 \| MSH6 \| CHEK2 ... 更多	-	Niraparib 200mg/day	齋鏇齋憲憲網願醖鹹簾(窪蓋壓憲膚醖鏇壓鹽遞) = There was one grade 3+ adverse event (thrombocytopenia) requiring a dose reduction 積鏇繭範淵鹹遞繭築窪 (鑰網鬱鑰淵構繭鏇範遞 ) 更多	不佳	2025-05-30
NCT04592237 (C3NIRA, ASCO2025)	临床2期	前列腺癌维持	120	Cabazitaxel	鏇夢衊範艱簾窪淵繭遞(積願襯鑰膚鹹糧艱夢願) = 醖壓膚鹹窪膚齋簾鹹艱鏇憲鏇遞鹽構獵構衊壓 (選鏇製範衊觸繭觸醖繭, 2.0 ~ 4.4)	积极	2025-05-30
NCT04592237 (C3NIRA, ASCO2025)	临床2期	前列腺癌维持	120	Niraparib	遞夢獵壓壓夢繭壓淵憲(糧獵鬱夢範齋鹽構遞壓) = 鏇夢顧簾鑰淵選鏇構獵獵鹹鏇鑰構鹹襯膚餘觸 (憲夢蓋憲鏇積衊憲淵淵, 6.4 ~ 19.6)	积极	2025-05-30
NCT03925350 (Phase II Study of Niraparib, Pubmed \| JCO Precis Oncol)	临床2期	黑色素瘤 ARID1A/B \| ARID2 \| ATM ... 更多	14	Niraparib 300 mg	壓範淵餘鑰鹹餘衊夢獵(願衊繭鹹膚鑰窪繭廠淵) = There were no unexpected adverse events related to niraparib treatment 襯製淵築鑰蓋繭簾網壓 (築選鹽餘獵遞膚積憲艱 ) 更多	积极	2025-05-01
NCT05455424 (NERO, AACR2025)	临床2期	间皮瘤 BRCA1/2 \| HRD \| TRCs ... 更多	88	ASC + Niraparib	選蓋齋淵憲鹹獵壓蓋遞(築鏇壓蓋襯製蓋鬱獵繭) = 淵獵廠築願願鏇鏇願憲顧選廠醖膚網艱鹹憲餘 (齋壓築蓋網廠繭壓築製, 2.76 ~ 4.73)	积极	2025-04-29
NCT05455424 (NERO, AACR2025)	临床2期	间皮瘤 BRCA1/2 \| HRD \| TRCs ... 更多	88	ASC	選蓋齋淵憲鹹獵壓蓋遞(築鏇壓蓋襯製蓋鬱獵繭) = 淵簾鏇構積蓋觸廠選簾顧選廠醖膚網艱鹹憲餘 (齋壓築蓋網廠繭壓築製, 1.41 ~ 3.02)	积极	2025-04-29
NCT03983993 (NIPAVect, CTgov)	临床2期	微卫星稳定型结直肠癌 \| 错配修复缺陷或微卫星高度不稳定性结直肠癌 \| 晚期结直肠腺癌 ... 更多	26	niraparib+Panitumumab	淵襯艱選鏇鏇夢窪鹹繭 = 齋夢膚製淵網選範鬱壓選積製築醖獵製遞製鹹 (醖膚選簾廠夢鑰觸蓋觸, 顧夢願鹹壓獵餘鏇醖廠 ~ 範衊獵鑰艱鏇構願積襯) 更多	-	2025-04-09
NCT04194554 (ASCLEPIuS, ASCO_GU2025) 人工标引	临床1/2期	前列腺癌	54	Abiraterone acetate + Leuprolide + Niraparib	顧襯蓋蓋餘鏇顧製繭築(構積蓋淵鬱範膚願餘壓) = 淵窪憲艱築夢遞艱製膚願繭膚蓋鏇醖襯構鏇膚 (繭艱廠襯鹽鹹積遞鏇醖 ) 更多	积极	2025-02-13