Combination Therapy of Senaparib and Bevacizumab for First-line Maintenance Therapy in Newly Diagnosed Advanced Homologous Recombination Proficient Ovarian Cancer Based on Exosome Protein Marker: a Single Arm, Prospective Clinical Study

This study is a Prospective, Single-arm, Phase II clinical trial. The purpose of this study is to find out if taking combination therapy of Senaparib and Bevacizumab is safe and works well for people with first-line maintenance therapy in newly diagnosed advanced homologous recombination proficient ovarian cancer, and explore relevant biomarkers for evaluating the efficacy of maintenance therapy through exosome. Researchers will look at the Progression-Free Survival, Overall Survival, safety, and any side effects.

开始日期2025-10-10

申办/合作机构

复旦大学

NCT06617923

/ Recruiting临床2期IIT

A Phase 2 Study of Senaparib in Combination With Temozolomide in ARID1A Mutation Associated Ovarian Cancer

This is a phase 2 study to test the effectiveness (anti-tumor activity) of the combination of the study drugs, Senaparib and Temozolomide, in patients with clear cell or endometrioid ovarian cancers that have ARID1A pathologic variants.

开始日期2025-02-06

申办/合作机构

The Sidney Kimmel Comprehensive Cancer Center

[+2]

NCT07019194

/ Completed临床1期

An Open-label, Randomized, Single-dose, Two-way Crossover Bioequivalence Study to Compare Two Strengths (10 mg and 20 mg) of Senaparib Capsules in Healthy Chinese Subjects Following Oral Administration Under Fasting Condition

开始日期2024-06-21

申办/合作机构

上海瑛派药业有限公司

100 项与塞纳帕利相关的临床结果

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100 项与塞纳帕利相关的转化医学

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100 项与塞纳帕利相关的专利（医药）

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项与塞纳帕利相关的文献（医药）

2025-05-01·JOURNAL OF CONTROLLED RELEASE

Multifunctional nanoparticle-mediated targeting of metabolic reprogramming and DNA damage response pathways to treat drug-resistant triple-negative breast cancer

Article

作者: Wang, Jue ; Wang, Cheng ; Cai, Zimin ; Sun, Chao ; Zhu, Sifeng ; Wu, Jibin ; Han, Xu

Multi-drug resistance and immunosuppressive triple-negative breast cancer (TNBC) is triggered by the Warburg effect, which promotes homologous recombination repair (HRR) and upregulates expression of P-glycoprotein (P-gp), in turn preventing DNA damage from chemotherapy and creating an immunosuppressive microenvironment. It is therefore of clinical relevance to develop an effective delivery system that targets metabolic reprogramming and DNA damage response pathways for the treatment of drug-resistant TNBC. Herein, a P-gp-inhibiting and GSH-responsive multifunctional drug carrier targeting integrin αvβ3 was synthesised for the delivery of Lonidamine-prodrug (M1, glycolysis inhibitor) and Senaparib (Se, Poly [ADP-ribose] polymerase inhibitor). The nanodrug delivery system (iPR@M1/Se nanoparticles) exhibit effective tumour penetration and P-gp inhibition, effectively inducing DNA damage and apoptosis in Olaparib-resistant TNBC cells in vitro, as well as a higher tumour inhibitory rate compared with that of Se (81.82 % ± 2.31 % vs 43.91 % ± 4.65 %) in vivo. Mechanistically, iPR@M1/Se nanoparticles not only reshaped the immunosuppressive microenvironment resulting from tumour glycolysis, but also downregulated the expression of HRR-related protein, fostering the cytoplasmic accumulation of DNA damage fragments, which induced activation of the cyclic GMP-AMP synthase (cGAS)/stimulator of interferon gene (STING) pathway. Experimental results show that iPR@M1/Se nanoparticles effectively promote dendritic cell maturation and T lymphocyte activation, which elicits long-term immune memory responses, and prevents tumour recurrence and lung metastasis. Therefore, these multifunctional nanoparticles have great potential and provide a clinically relevant and valuable option for Olaparib-resistant TNBC.

2025-04-01·JOURNAL OF BIOLOGICAL CHEMISTRY

Duplexed CeTEAM drug biosensors reveal determinants of PARP inhibitor selectivity in cells

Article

作者: Alam, Seher ; Rotili, Dante ; Altun, Mikael ; Lovric, Alen ; Fabbrizi, Emanuele ; Pires, Maria J ; Valerie, Nicholas C K

Poly (ADP-ribose) polymerase (PARP) inhibitors (PARPi) targeting PARP1 and PARP2 have revolutionized cancer therapy by selectively killing cancer cells with defective DNA repair. However, achieving PARP1 or PARP2-selective inhibitors is difficult due to structural homology. Selectivity profiling is typically done with purified proteins, but these lack the complexity of intracellular environments and could therefore be inaccurate. Here, we duplex PARP1 L713F-GFP and PARP2 L269A-mCherry cellular target engagement by accumulation of mutant (CeTEAM) drug biosensors to systematically characterize binding and cell cycle alterations of 27 PARPi. Our results reveal that most PARPi are equipotent for both PARPs, including the next-generation drug, senaparib. However, benzimidazole carboxamide (niraparib) derivatives demonstrated PARP1-selective tendencies, while phthalazinones (olaparib) favored PARP2. AZD5305, a reported PARP1-selective inhibitor with characteristics of both series, was the exception and appears ∼1600-fold more potent toward PARP1. In agreement with current understanding, we see that trapping-associated S/G2-phase transitions positively correlate with PARP1/2 binding potency, while some potent binders, such as veliparib, did not - likely reflecting their allosteric influence on DNA retention. We also assessed the effect of the PARP1/2 active site component, histone PARylation factor 1, on intracellular PARPi binding and see that its depletion elicits slight deviations in apparent binding potency, while contributing additively to trapping-like phenotypes. The PARP1/2 CeTEAM platform thus provides a structural roadmap for the development of selective PARPi and should facilitate the discovery of targeted therapies. Furthermore, our results highlight that multiplexing CeTEAM biosensors and layered genetic perturbations can systematically profile determinants of intracellular drug selectivity.

2025-01-02·MOLECULAR CANCER THERAPEUTICS

The Discovery of a Potent PARP1 Inhibitor Senaparib

Article

作者: Guo, Mingchuan ; Cai, Sui X. ; Tian, Ye E. ; Jiang, Yangzhen ; Ma, Ning ; Wang, Xiaozhu

Abstract:

PARP1 is a critical enzyme involved in DNA damage repair. It belongs to a superfamily of proteins and catalyzes poly(ADP-ribosyl)ation (PARylation). PARP1 inhibitors are effective to treat tumors that have homologous recombination deficiency such as those with BRCA1/2 mutations. The PARP1 inhibitors that have been approved by FDA inhibit both PARP1 and PARP2. PARP2 has also been suggested to play a similar function in DNA repair as PARP1. In addition to inhibiting PARP1 enzymatic activities, PARP1 inhibitors cause the PARP1 enzyme to be “trapped” on DNA, stalling the DNA replication fork and eventually causing double-strand DNA breaks and cell death. Here, we report a PARP1 inhibitor, Senaparib, which has a novel chemical structure and high potency inhibiting PARP1/2 enzymes. Senaparib was highly potent in cell viability tests against tumor cells with BRCA1/2 mutations. It was efficacious in cell line-derived and patient-derived xenograft models in tumors harboring BRCA1/2 mutations. In combination studies, Senaparib used with temozolomide had shown strong synergistic cytotoxicity in both in vitro and in vivo experiments. Senaparib represents a novel class of PARP1 inhibitors that can be used for the treatment of cancer. A phase III clinical study of Senaparib for maintenance treatment following first-line chemotherapy in patients with advanced ovarian cancer has met its primary endpoint, and a new drug application of Senaparib has been accepted by the National Medical Products Administration of China for review.

120

项与塞纳帕利相关的新闻（医药）

2025-08-18

·impacttherapeutics.com

英派药业宣布欧洲药品管理局已受理塞纳帕利胶囊用于卵巢癌一线维持治疗的上市许可申请

中国上海，2025年8月15日 - 英派药业，一家专注于发现和开发基于合成致死作用机制的靶向抗癌治疗药物的生物技术公司，欣然宣布，塞纳帕利 (Senaparib)用于晚期卵巢癌一线维持治疗的上市许可申请（MAA）已获得欧洲药品管理局（EMA）受理。这是继 2025 年 1 月中国国家药品监督管理局（NMPA）批准塞纳帕利作为适用于晚期上皮性卵巢癌、输卵管癌或原发性腹膜癌成人患者在一线含铂化疗达到完全缓解或部分缓解后的维持治疗之后的又一里程碑。此次申报是基于一项随机、双盲、安慰剂对照、多中心III期临床研究（FLAMES研究）。其研究结果显示塞纳帕利维持治疗能够显著延长晚期卵巢癌患者的无进展生存期（PFS），无论患者是否伴有乳腺癌易感基因（BRCA）突变，均能从塞纳帕利治疗中获益。同时，塞纳帕利耐受性良好，安全性可控。该研究数据已于2024年5月在Nature Medicine 上发表。1 英派药业首席执行官蔡遂雄博士表示：“我们很高兴塞纳帕利的上市许可申请获得欧洲药品管理局的受理。这是英派药业走向国际化的重要里程碑。我们期待塞纳帕利能尽快进入海外市场，惠及全球患者。” 【关于卵巢癌】卵巢癌是最常见的致死性女性生殖道恶性肿瘤之一。据GLOBOCAN 2020数据，，全球卵巢癌的年新发病例数达31万，死亡病例数达21万2。由于卵巢癌早期症状隐匿且非特异，约80%的患者确诊时已为晚期，5年生存率仅有40%3。尽管卵巢癌经过初始含铂化疗后可以得到缓解，但大多数患者都不可避免面临复发4。近年来，PARP抑制剂正在改变卵巢癌的治疗格局，其维持治疗可延长一线含铂化疗后的缓解时间，延缓复发5。 1. 本材料旨在传递前沿信息，无意向您做任何产品的推广，不作为临床用药指导。 2. 若您想了解具体疾病诊疗信息，请遵从医疗卫生专业人士的意见与指导。【关于FLAMES研究】 FLAMES研究（IMP4297-301，NCT04169997）是一项随机、双盲、安慰剂对照、多中心的Ⅲ期临床研究，旨在评价一线含铂化疗达到完全缓解（CR）或部分缓解（PR）后塞纳帕利单药维持治疗FIGO III-IV期卵巢癌患者的有效性和安全性。FLAMES研究结果显示，塞纳帕利维持治疗能够显著延长晚期卵巢癌患者的中位无进展生存期（mPFS）（未达到 vs 13.6月, HR 0.43， P < 0.0001），且不论患者的BRCA基因表达如何，均能从塞纳帕利治疗中获益。同时，塞纳帕利耐受性良好，安全性可控。此外，塞纳帕利在具有同源重组缺陷(HRD)和同源重组修复正常（HRR）亚组的患者中均显示出显著PFS获益，突显其广泛的临床应用潜力。此研究结果有力支持了塞纳帕利单药作为新诊断卵巢癌患者一线全人群维持治疗的标准方案。该研究数据于2023年欧洲肿瘤内科学会（ESMO）大会和2024年中国临床肿瘤学会（CSCO）大会等重要学术会议上，通过口头报告的形式展示，并发表在国际顶级医学期刊《Nature Medicine》上。1 【关于 Senaparib（派舒宁®）】塞纳帕利是英派药业研发的一种强效、新型PARP 1/2抑制剂。其独特的分子结构具有较高的体外和体内活性、优异的靶点选择性和较宽的安全窗。FLAMES研究为塞纳帕利获得NMPA批准提供了支持。【关于英派药业】英派药业是一家处于商业化阶段的全球性、创新驱动型生物技术公司，也是全球少数专注于合成致死（synthetic lethality）原理开发新型精准肿瘤疗法的公司之一。我们的愿景是打造全球领先的合成致死平台，提供更优的靶向癌症治疗方案，显著改善实体瘤治疗现状。我们的产品管线处于全球合成致死领域前沿，旨在解决重大未满足的医疗需求，树立新的治疗标准。公司管线包括PARP抑制剂塞纳帕利（Senaparib/IMP4297）、ATR抑制剂（IMP9064）、Wee1抑制剂（IMP7068）、PARP1选择性抑制剂 (IMP1734及IMP1707，与美国Eikon Therapeutics合作开发)以及多个其他合成致死靶点抑制剂。更多信息请浏览www.impacttherapeutics.com 投资者关系及媒体英派药业 +86 21 6841 1121 IR@impacttherapeutics.com PR@impacttherapeutics.com 【参考文献】 1.Nature Medicine | Volume 30 | June 2024 | 1612–1621 2.Sung H, et al. CA Cancer J Clin. 2021; 71(3):209-49 3.Morgan RJ Jr, et al. J Natl Compr Canc Netw. 2016; 14:1134-63. 4.Jayson GC, et al. Lancet. 2014;384(9951):1376–88. 5. Khalique S, et al. Curr Opin Oncol. 2014;26(5):521–8.

临床3期上市批准

2025-08-15

·英派药业

EMA Accepts MAA of Senaparib for 1L Maintenance Therapy in OC

NEWS SHANGHAI, August 15th, 2025 - IMPACT Therapeutics (“IMPACT”), a biotechnology company focused on the discovery and development of targeted anti-cancer therapeutics based on synthetic lethality, is pleased to announce that the European Medicines Agency (EMA) has accepted the Marketing Authorization Application (MAA) for Senaparib, a next-generation PARP1/2 inhibitor discovered and developed by IMPACT, as a first-line maintenance treatment for advanced ovarian cancer. This milestone follows Senaparib’s approval by the China National Medical Products Administration (NMPA) in January 2025 as monotherapy for the maintenance treatment of adult patients with advanced epithelial (FIGO Stages III and IV) high-grade ovarian, fallopian tube or primary peritoneal cancer who are in response (complete or partial) following completion of first-line platinum-based chemotherapy. This MAA submission is based on the randomized, double-blind, placebo-controlled, multicenter phase III FLAMES study (FLAMES Study). The results of the FLAMES Study showed that Senaparib demonstrated significant improvement in median progression-free survival (mPFS) compared to placebo, irrespective of BRCA status. Meanwhile, Senaparib was well-tolerated with a manageable safety profile. The results were published in May 2024 in the internationally renowned medical journal Nature Medicine.1 Dr. Sui Xiong Cai, CEO of IMPACT, said: “We are delighted that the MAA for Senaparib has been accepted by the EMA. This marks a pivotal milestone in IMPACT’s journey toward globalization. With this acceptance, we anticipate expedited entry into overseas markets to deliver this innovative therapy to patients worldwide.” - This material is intended to provide cutting-edge information, and is not meant to promote any products or serve as clinical medication guidance. - If you wish to obtain specific disease diagnosis and treatment information, please follow the advice and guidance of medical and healthcare professionals. About Ovarian Cancer Ovarian cancer is one of the most common lethal female reproductive malignancies. According to GLOBOCAN 2020 data, the global incidence of ovarian cancer is amounted to 310,000 cases and mortality is amounted to 210,000.2 Due to the insidious and non-specific early symptoms of ovarian cancer, about 80% of patients are already in advanced stage when they are diagnosed, and the 5-year survival rate is only 40%.3 Although ovarian cancer may be resolved after initial platinum-based chemotherapy, most patients face recurrence, highlighting a significant unmet clinical need for treatment in the ovarian cancer patient population.4 In recent years, PARP inhibitors have transformed the therapeutic landscape for ovarian cancer, with maintenance therapy extending the duration of sustained remission after platinum-based chemotherapy and delaying disease recurrence.5 About the FLAMES Study The FLAMES Study (IMP4297-301, NCT04169997) is a randomized, double-blind, placebo-controlled, multicenter Phase III clinical study designed to evaluate the efficacy and safety of Senaparib as a single-agent maintenance treatment for patients with FIGO Stage III-IV ovarian cancer who have achieved a complete response (CR) or partial response (PR) following first-line platinum-based chemotherapy. The results of the FLAMES Study showed that Senaparib demonstrated significant improvement in median PFS compared to placebo (PFS not reached vs 13.6 months, HR 0.43, P < 0.0001), irrespective of BRCA status. Senaparib demonstrated a tolerable safety profile, with no noticeable safety issues. 1 The results also indicated that both homologous recombination deficiency (HRD) positive and HRD negative populations derived benefit from Senaparib maintenance therapy, highlighting the potential of Senaparib for broad clinical application. The results of this study will strongly support Senaparib as the Standard of Care for first-line maintenance therapy in patients with newly diagnosed ovarian cancer. The top-line results of the study were initially presented as a late-breaking oral presentation at ESMO in 2023 and at CSCO 2024, and published in the international renowned medical journal Nature Medicine. 1 About Senaparib (派舒宁®) Senaparib is a potent and novel PARP 1/2 inhibitor discovered and developed by IMPACT. Its unique molecular structure provides high in vitro and in vivo activity, exceptional target selectivity and wide safety window. Senaparib’s approval by the NMPA was supported by the FLAMES Study. About IMPACT Therapeutics IMPACT Therapeutics is a globally focused, innovation-driven biotechnology company at the commercial stage, and one of the few biotechnology companies worldwide dedicated to the discovery and development of novel precision oncology therapeutics based on the synthetic lethality approach. IMPACT’s vision is to build a leading global synthetic lethality franchise that delivers better targeted cancer therapies and makes a meaningful impact on the treatment of solid tumors. IMPACT’s pipeline is among the most advanced in the synthetic lethality field globally, with product candidates designed to address significant unmet medical needs and poised to set new standards of care. IMPACT’s pipeline includes the PARP1/2 inhibitor Senaparib (IMP4297), ATR inhibitor (IMP9064), Wee1 inhibitor (IMP7068), PARP1 selective inhibitors (IMP1734 and IMP1707, co-developed with Eikon Therapeutics), and multiple other synthetic lethality target inhibitors. For additional information, please visit www.impacttherapeutics.com IMPACT Therapeutics Contact: +86 21 6841 1121 IR@impacttherapeutics.com PR@impacttherapeutics.com References 1. Nature Medicine | Volume 30 | June 2024 | 1612–1621 2. Sung H, et al. CA Cancer J Clin. 2021; 71(3):209-49 3. Morgan RJ Jr, et al. J Natl Compr Canc Netw. 2016; 14:1134-63. 4. Jayson GC, et al. Lancet. 2014;384(9951):1376–88. 5. Khalique S, et al. Curr Opin Oncol. 2014;26(5):521–8.

CSCO会议临床结果

2025-08-13

·药明康德

致敬时代 | 从50%死亡率到生存率接近翻倍：卵巢癌治疗的突破之路

编者按：2025年，药明康德迎来创立25周年的重要里程碑。值此契机，我们向所有与我们共同书写产业变革篇章的科学家、医药人和投资者致以衷心感谢与诚挚敬意，也特别推出“致敬时代”系列，回顾全球同仁如何借助科学与合作的力量，不断拓展治疗边界、改善患者命运。四分之一个世纪的坚守，只为加速每一款新药的诞生。下一个25年，我们将继续心怀感恩与敬畏，依托独特的CRDMO模式，与全球伙伴携手同行，共赴健康未来。在全球女性癌症谱系中，卵巢癌一直以“难治”著称。“神刊”CA：A Cancer Journal for Clinicians杂志发布的2025年癌症统计报告显示，卵巢癌的致死率在女性癌症中高居第六位。导致卵巢癌如此难治的原因之一是其早期症状十分隐匿，约70%的患者在确诊时已处于晚期。再加上复发率高、预后较差等因素，卵巢癌也成为了主要的“妇女杀手”之一。近十余年来，随着靶向治疗时代的开启和新型分子疗法的不断涌现，卵巢癌的治疗格局迎来了新的转机。当我们回望整个卵巢癌治疗的发展史，不仅能看到各类治疗手段的迭代演进，更能感受到全球各界的协同创新，共同推动着卵巢癌治疗领域的每一次重大突破。图片来源：123RF 从开创性手术到现代治疗在人类对抗卵巢癌的医学探索史上，1809年是一个重要的开端。那年圣诞节，美国医生以法莲·麦克道尔（Ephraim McDowell）在没有麻醉和消毒的条件下，成功为一名46岁女性切除了重达10公斤的卵巢肿瘤。这也是首个被详细记录的卵巢肿瘤切除手术。这位被后世尊为“卵巢手术之父”的医生可能想象不到，他这次冒险的手术开创了一个全新的医学领域。受限于技术条件，在那个年代做手术的危险性可能比癌症本身还致命。直到大半个世纪后的1882年，英国外科医生托马斯·斯宾塞·威尔斯（Thomas Spencer Wells）改良了卵巢手术技术，并将无菌技术和麻醉引入手术，才将当时手术的死亡率从惊人的50%降至11%。到了20世纪初，英国著名的妇科外科医生维克多·邦尼（Victor Bonney）又进一步推动了妇科手术的进步——他发明的“邦尼蓝”消毒液改善了术中消毒流程，大幅降低了术后感染率。在一代代医学工作者的不懈探索与临床实践积累下，手术治疗就这么一步步地成为了卵巢癌的主要治疗手段。图片来源：123RF 20世纪中叶，随着放射治疗的引入，卵巢癌治疗进入了新的阶段。那时，全腹放疗（WAR）被用于治疗卵巢癌的腹腔转移。然而，该疗法始终面临着剂量选择的两难困境：若采用低剂量放疗以保护腹腔内的正常器官，则难以达到理想的肿瘤控制效果；而若提高剂量以确保疗效，又往往会产生严重的急性毒性反应使患者无法耐受。更棘手的是，高达20%的患者会出现放射性肺炎，15%会遭受不可逆的肝损伤，这些严重的长期毒性让医生们不得不寻找更安全的替代方案。转机出现在20世纪70年代。随着能破坏癌细胞DNA结构的铂类化疗药物的问世，卵巢癌治疗终于迎来了突破。1978年，首款用于治疗卵巢癌的铂类抗肿瘤药物顺铂获得了FDA批准，从这种治疗中受益的患者人数达数百万。随后问世的第二代铂类药物卡铂则能够在保持疗效的同时大幅降低不良反应。进入80年代后，紫杉烷类药物的发现进一步为卵巢癌患者提供了更多的治疗选择。这类源自天然植物的抗癌药物通过独特的微管稳定机制发挥作用，还能与铂类药物形成互补。基于良好的临床试验结果，肿瘤切除术后辅以铂类（顺铂/卡铂）联合紫杉烷类（紫杉醇/多西他赛）化疗成为了卵巢癌的新一代标准治疗方案。从“无差别杀伤”到“精准打击” 自基于铂类药物的组合化疗成为标准治疗后，晚期卵巢癌患者的5年生存率提高到了约25%，但仍然不是一个能够令人满意的数字。约80%的患者在接受一线治疗后有望获得完全缓解，然而残酷的是，60%-80%患者会在18个月内因化疗耐药复发，即便二线治疗有效，85%患者仍会在两年内再次出现疾病进展。对于这些出现完全缓解或部分缓解的患者来说，如何在化疗后继续保持“缓解状态”有着巨大的未竟医疗需求。 21世纪初，靶向治疗时代拉开了帷幕，也为卵巢癌的治疗带来了突破。这一时期的医学发展开始从“无差别杀伤”的传统化疗模式，转向针对肿瘤特定分子特征的“精准打击”策略。图片来源：123RF 2011年，欧洲率先批准了抗血管生成药物Avastin（bevacizumab，贝伐珠单抗）与铂-紫杉烷类化疗的联合方案，用于晚期卵巢癌的一线治疗及维持治疗。该药物通过抑制肿瘤血管生成来“饿死”癌细胞，与化疗联用可显著延长无进展生存期。三年后，美国FDA也批准了该药在铂类耐药复发性卵巢癌二线治疗中的应用。作为一类在卵巢癌领域取得突破的生物制品，贝伐珠单抗虽然能暂时延缓疾病进展，却难以显著延长患者的总生存时间，加上该药有可能引发高血压、血栓甚至胃肠道穿孔等不良反应的风险，医学界寄希望于找到更加安全有效的新疗法。 “合成致死”，针对卵巢癌的常见突变 2014年，随着首款PARP抑制剂的问世，卵巢癌的治疗格局发生了革命性的变化。这一突破可追溯至1922年哥伦比亚大学Calvin Bridges博士发现的“合成致死”现象：当两个特定基因同时发生突变时会导致生物体死亡，而这两个基因单独突变却不会产生致命影响。半个世纪后，一些科学家基于这个现象提出，合成致死可能为抗癌药物开发提供新的策略。这一想法终于在2005年得到了验证——两支研究团队在《自然》杂志上发表里程碑成果，首次证实了PARP抑制剂与BRCA突变存在“合成致死”效应。BRCA基因突变会破坏癌细胞修复DNA双链断裂的能力，而PARP抑制剂则能阻断另一条修复单链断裂的通路。当这两种修复机制同时被抑制时，癌细胞就会因无法修复DNA损伤而死亡，这就是“合成致死”效应的具体体现。 ▲合成致死作用机制在抗癌药物开发中的应用（图片来源：参考资料[6]）这一突破性发现也为卵巢癌治疗开辟了新方向。由于约15%的卵巢癌患者携带BRCA基因突变，研究人员意识到，PARP抑制剂也有可能成为卵巢癌患者的理想靶向治疗选择。经过近十年的临床验证，2014年12月，首款PARP抑制剂Lynparza（olaparib，奥拉帕利）获得FDA批准上市，用于治疗携带BRCA种系突变的晚期卵巢癌患者。奥拉帕利的成功催生了更多PARP抑制剂的研发。2016年，Zejula（niraparib，尼拉帕利）的临床试验数据进一步扩展了受益人群，显示其对同源重组修复缺陷（HRD）阳性的非BRCA突变患者同样有效。截至目前，全球上市的PARP抑制剂已达7款，其中6款都获批用于治疗卵巢癌，除了奥拉帕利和尼拉帕利，还有派舒宁（塞纳帕利）、百汇泽（帕米帕利）、艾瑞颐（氟唑帕利）和Rubraca（rucaparib）。这些药物通过精准打击癌细胞的DNA修复缺陷，显著延长了患者的无进展生存期。随着在一线治疗中引入PARP抑制剂维持治疗，卵巢癌患者的生存率进一步提高。在一项临床试验中，晚期高风险患者的5年生存率已超过40%。这一突破性进展源于多重因素的协同作用：手术技术的革新使肿瘤减灭更加彻底，化疗方案的优化提升了初始治疗效果，再加上PARP抑制剂维持治疗的精准应用和靶向药物的合理选择延迟了肿瘤复发的进程。百花齐放：从靶向药到免疫疗法在PARP抑制剂取得显著成效的同时，针对其他靶点的创新疗法也相继问世，进一步丰富了卵巢癌的治疗选择。以叶酸受体α（FRα）靶点为例，尽管FRα在35-40%的卵巢癌中高表达，但长期以来缺乏有效靶向药物。2022年11月，全球首个靶向FRα的抗体偶联药物（ADC）Elahere（mirvetuximab soravtansine）获得FDA加速批准。这款ADC通过将抗FRα单抗与细胞毒性分子DM4偶联，实现了对铂类耐药卵巢癌的精准打击。新闻稿指出，该疗法是首个在铂类耐药卵巢癌患者上显示带来总生存期（OS）改善的疗法。在关键的3期临床试验中，Elahere组患者的中位OS为16.46个月，较研究者选择（IC）化疗组的12.75个月延长了近4个月。在对化疗的应答率较低的卵巢癌亚型治疗方面，2025年5月，FDA加速批准RAF/MEK抑制剂avutometinib联合FAK抑制剂defactinib方案（Avmapki Fakzynja Co-Pack）用于KRAS突变型复发性低级别浆液性卵巢癌（LGSOC）。Avutometinib能够同时抑制RAF和MEK，克服了传统MEK抑制剂的代偿性激活问题。在Avastin的基础上，新一代重组人源化抗血管内皮生长因子（VEGF）抗体苏维西塔单抗于今年7月获中国国家药品监督管理局（NMPA）批准，可与紫杉醇、多柔比星脂质体或拓扑替康联用治疗铂耐药后接受过不超过1种系统治疗的成人复发性卵巢癌、输卵管癌或原发性腹膜癌的治疗。在一项3期临床试验中，与对照组相比，苏维西塔单抗组也呈现出OS获益趋势（16.07个月对比14.88个月）。值得一提的是，苏维西塔单抗的临床应用不受前线VEGF通路治疗和PARP抑制剂靶向治疗的限制，与化疗联用也不受化疗药物种类限制。除以上靶点外，有极少数卵巢癌患者（约1-2%）存在着NTRK基因融合突变，这种突变会驱动异常细胞生长和癌症进展。Vitrakvi（larotrectinib，拉罗替尼）和Rozlytrek（entrectinib，恩曲替尼）可阻断突变NTRK基因产生异常蛋白质。这些药物能够用于治疗那些存在NTRK基因突变、且经过其他治疗方案后病情仍然进展的晚期卵巢癌患者。在靶向治疗取得突破的同时，免疫治疗也为卵巢癌患者带来了新的希望。人体免疫系统通过“检查点”机制来防止攻击正常细胞，而癌细胞常会利用这一机制逃避免疫监视。以PD-1/PD-L1抑制剂为代表的免疫检查点抑制剂，通过阻断这一逃逸通路，能够重新激活T细胞对癌细胞的杀伤作用。 PD-1抑制剂Keytruda（pembrolizumab，帕博利珠单抗）、Jemperli（dostarlimab）和百泽安（替雷利珠单抗）均已获得监管批准，用于治疗不可切除或转移性微卫星高度不稳定型（MSI-H）或错配修复基因缺陷型（dMMR）的晚期实体瘤患者，其中也包括卵巢癌患者。这些靶向治疗和免疫疗法的不断涌现，使得卵巢癌治疗从传统的“一刀切”模式逐步迈向精准化、个体化的新时代。随着对卵巢癌分子机制认识的深入和更多创新药物的开发，临床医生能够根据患者的分子特征选择最适合的治疗方案，为不同亚型的卵巢癌患者带来更有针对性的治疗选择。一体化平台赋能卵巢癌新药开发从两个世纪前开创性的卵巢切除术，到如今的精准治疗，人类对抗卵巢癌的征程已走过漫长而艰辛的道路。一方面看，卵巢癌的治疗手段不断革新——从手术加化疗，到靶向治疗，再到更多新兴疗法，给患者带来了新的希望。但另一方面，晚期卵巢癌患者的五年生存率仍未突破50%的大关。这一数字时刻提醒我们：与这个“沉默杀手”的较量依然任重道远。根据公开资料，目前有数百种卵巢癌疗法已进入临床开发阶段，针对百余种不同的靶点。长期以来，药明康德都在支持全球合作伙伴从药物研究（R）、开发（D）到商业化生产（M）各个阶段的需求，通过独特的一体化、端到端CRDMO模式，助力突破性疗法加速研发进程、早日惠及患者。我们很高兴能赋能卵巢癌新药的开发，也将继续与全球合作伙伴携手同行，共同推动卵巢癌治疗的突破，让更多患者迎来曙光！参考资料： [1] Tavares V, Marques IS, Melo IG, Assis J, Pereira D, Medeiros R. Paradigm Shift: A Comprehensive Review of Ovarian Cancer Management in an Era of Advancements. Int J Mol Sci. 2024 Feb 3;25(3):1845. doi: 10.3390/ijms25031845. PMID: 38339123; PMCID: PMC10856127. [2] Lumish MA, Kohn EC, Tew WP. Top advances of the year: Ovarian cancer. Cancer. 2024 Mar 15;130(6):837-845. doi: 10.1002/cncr.35135. Epub 2023 Dec 15. PMID: 38100616. [3] Barber HR. New frontiers in ovarian cancer diagnosis and management. Yale J Biol Med. 1991 Mar-Apr;64(2):127-41. PMID: 1721478; PMCID: PMC2589481. [4] Ozols RF. Ovarian cancer. Semin Surg Oncol. 1990;6(6):328-38. doi: 10.1002/ssu.2980060607. PMID: 2263808. [5] European contributions to the diagnosis and treatment of ovarian cancer: a historical and modern perspective. Retrieved August 7, 2025, from https://www.oncopedia.wiki/contributions/european-contributions-to-the-diagnosis-and-treatment-of-ovarian-cancer-a-historical-and-modern-perspective [6] Ngoi et al., (2024). Synthetic lethal strategies for the development of cancer therapeutics. Nature Reviews Clinical Oncology, https://doi.org/10.1038/s41571-024-00966-z 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

放射疗法

100 项与塞纳帕利相关的药物交易

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适应症	国家/地区	公司	日期
输卵管癌	中国	上海英派药业有限公司	2025-01-14
卵巢上皮癌	中国	上海英派药业有限公司	2025-01-14
原发性腹膜癌	中国	上海英派药业有限公司	2025-01-14

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适应症	最高研发状态	国家/地区	公司	日期
卵巢癌	申请上市	欧盟	南京英派药业股份有限公司	2025-08-15
转移性去势抵抗性前列腺癌	临床2期	美国	上海瑛派药业有限公司	2021-12-31
转移性去势抵抗性前列腺癌	临床2期	中国	上海瑛派药业有限公司	2021-12-31
转移性去势抵抗性前列腺癌	临床2期	澳大利亚	上海瑛派药业有限公司	2021-12-31
晚期恶性实体瘤	临床2期	美国	上海英派药业有限公司	2021-09-28
晚期恶性实体瘤	临床2期	澳大利亚	上海英派药业有限公司	2021-09-28
晚期恶性实体瘤	临床2期	韩国	上海英派药业有限公司	2021-09-28
广泛期小细胞肺癌	临床2期	美国	上海英派药业有限公司	2021-09-28
广泛期小细胞肺癌	临床2期	澳大利亚	上海英派药业有限公司	2021-09-28
广泛期小细胞肺癌	临床2期	韩国	上海英派药业有限公司	2021-09-28

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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


NCT04169997 (FLAMES, Nat Med) 人工标引	临床3期	卵巢癌一线 BRCA1 Mutation \| BRCA2 Mutation	404	senaparib 100 mg	淵襯鬱製衊膚鹹範製鏇(齋鹹顧壓積築願繭獵淵) = 憲醖鏇鑰觸鏇繭衊壓鬱齋獵顧憲壓鑰遞鹽願襯 (夢齋選淵積鹹範淵觸積 ) 更多	积极	2024-05-15
				placebo	淵襯鬱製衊膚鹹範製鏇(齋鹹顧壓積築願繭獵淵) = 範夢遞觸積簾醖齋簾衊齋獵顧憲壓鑰遞鹽願襯 (夢齋選淵積鹹範淵觸積 ) 更多
NCT04089189 (SABRINA, ESMO 12023 \| ESMO 22023) 人工标引	临床2期	卵巢癌 BRCA1 Mutation \| BRCA2 Mutation	93	Senaparib 100 mg	壓構獵膚鑰齋夢製鹹膚(夢蓋窪願夢鬱鹹憲壓壓) = 齋構構齋積餘糧糧憲鹽製築夢顧簾製憲艱鏇構 (窪淵衊製鬱夢衊夢鹹繭, 86.2 ~ 97.5) 更多	积极	2023-10-22
NCT04169997 (FLAMES, ESMO2023) 人工标引	临床3期	卵巢癌维持	404	Senaparib	繭鏇糧構獵願窪蓋蓋餘(選鬱醖觸夢襯鹹襯襯襯) = 製製願餘衊餘網醖襯艱淵鏇夢選鬱膚繭構蓋夢 (襯糧糧鏇製壓廠衊衊鹽 ) 更多	积极	2023-10-20
				Placebo	繭鏇糧構獵願窪蓋蓋餘(選鬱醖觸夢襯鹹襯襯襯) = 顧壓範繭膚廠鹽範膚淵淵鏇夢選鬱膚繭構蓋夢 (襯糧糧鏇製壓廠衊衊鹽 ) 更多
FLAMES study (ESGO2023)	临床3期	卵巢癌维持 high-grade serous \| endometrioid tumors	404	Senaparib	遞鏇襯範齋蓋遞膚鬱醖(範壓選蓋蓋壓壓獵觸壓) = 簾遞鬱築憲醖鑰憲積淵夢淵選繭襯遞觸夢繭網 (艱網簾範糧繭願憲淵願 )	积极	2023-09-28
				Placebo	遞鏇襯範齋蓋遞膚鬱醖(範壓選蓋蓋壓壓獵觸壓) = 膚網壓鬱鏇蓋選鏇壓鬱夢淵選繭襯遞觸夢繭網 (艱網簾範糧繭願憲淵願 )
NCT04434482 (WCLC2023) 人工标引	临床1/2期	广泛期小细胞肺癌	42	Senaparib + Temozolomide	憲鑰願積選願簾糧蓋襯(齋觸廠膚願範鬱獵觸夢) = 醖醖構醖鏇鬱廠廠選遞壓獵淵遞襯構糧膚願繭 (淵廠鏇鏇夢獵製夢夢鬱, 5.4 ~ 28.5) 更多	积极	2023-09-12
				Senaparib + Temozolomide (Platinum sensitive)	憲鑰願積選願簾糧蓋襯(齋觸廠膚願範鬱獵觸夢) = 網憲構鏇鹹簾廠壓構願壓獵淵遞襯構糧膚願繭 (淵廠鏇鏇夢獵製夢夢鬱, 2.4 ~ 30.2) 更多
NCT03508011 (Pubmed)	临床1期	晚期恶性实体瘤	57	Senaparib	窪壓淵遞鬱窪齋夢顧鑰(觸簾壓糧齋壓簾窪淵鹹) = 蓋積廠積網遞鹽積範鬱製糧積選網廠構襯鏇網 (鏇範顧製鏇願衊選鏇觸 ) 更多	-	2023-06-20
NCT03507543 (Pubmed)	临床1期	晚期恶性实体瘤	39	Senaparib	鹹醖遞壓顧網簾觸衊糧(壓餘遞衊艱蓋網觸獵壓) = Most treatment-emergent adverse events were grade 1-2 (91%). Seven patients (17.9%) reported hematologic treatment-emergent adverse events. Treatment-related adverse events occurred in eight patients (20.5%), and the most frequent was nausea (7.7%). Two deaths were reported after the end of study treatment, one of which was considered a complication from senaparib-related bone marrow failure. 製顧夢膚顧網廠廠糧願 (遞糧膚積願構鬱糧獵範 )	-	2023-01-31
NCT04434482 (ASCO2022) 人工标引	临床1期	广泛期小细胞肺癌 \| HR阳性/HER2低表达实体瘤	14	Senaparib+Temozolomide	選壓淵糧艱鏇顧鏇築獵(積膚淵憲鹽艱衊範構獵) = The MTD and RP2D were determined as: senaparib 80 mg plus temozolomide 20 mg. 糧範夢鑰衊醖齋齋觸築 (簾製襯簾衊顧簾襯壓壓 ) 更多	积极	2022-06-02