A Randomized, Open-Label Phase 3 Study of Azenosertib Versus Investigator's Choice of Chemotherapy in Platinum-Resistant High-Grade Serous Ovarian, Primary Peritoneal, or Fallopian Tube Cancers Positive for Cyclin E1 Protein Expression

This is a randomized, Phase 3 trial designed to evaluate the efficacy and safety of azenosertib compared to Investigator's choice of chemotherapy in subjects with platinum-resistant ovarian cancer whose tumors are positive for cyclin E1 protein expression.

开始日期2026-04-17

申办/合作机构

K-Group Beta, Inc.

[+1]

NCT06369155

/ Recruiting临床2期IIT

A Biomarker Study of the Wee1 Inhibitor Azenosertib (ZN-c3) in Women With Recurrent or Persistent Uterine Serous Carcinoma

This research study is being done to investigate how Azenosertib affects tumor cells of persistent or recurrent uterine serous carcinoma.
The name of the study drug involved in this study is:
-Azenosertib (a type of Wee1 inhibitor)

开始日期2025-03-05

申办/合作机构

Dana-Farber Cancer Institute, Inc.

[+2]

NCT06364410

/ Recruiting临床1期IIT

Phase 1 Study of Trastuzumab Deruxtecan (DS-8201a) in Combination With Azenosertib (ZN-c3) in HER2-Expressing/Amplified Gastric/Gastroesophageal Junction Cancer and Other Solid Tumors

This phase I trial tests the safety, side effects, and best dose of azenosertib in combination with trastuzumab deruxtecan in treating patients with HER2-positive gastric or gastroesophageal junction cancer and other HER2-positive solid tumors that have spread to nearby tissue or lymph nodes (locally advanced), that have spread from where it first started (primary site) to other places in the body (metastatic), or that cannot be removed by surgery (unresectable). Azenosertib is in a class of medications called kinase inhibitors. It inhibits a protein called Wee1. Inhibition of the Wee1 protein can make tumor cells more vulnerable to chemotherapy drugs, leading to tumor cell death. Trastuzumab deruxtecan is in a class of medications called antibody-drug conjugates. It is composed of a monoclonal antibody, called trastuzumab, linked to a chemotherapy drug, called deruxtecan. Trastuzumab attaches to HER2 positive cancer cells in a targeted way and delivers deruxtecan to kill them. Giving azenosertib in combination with trastuzumab deruxtecan may be safe, tolerable, and/or more effective in treating patients with locally advanced, metastatic, or unresectable HER2-positive gastric, gastroesophageal junction, or other solid tumors, compared to just trastuzumab deruxtecan alone.

开始日期2025-02-03

申办/合作机构

National Cancer Institute

100 项与 Azenosertib 相关的临床结果

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100 项与 Azenosertib 相关的转化医学

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100 项与 Azenosertib 相关的专利（医药）

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项与 Azenosertib 相关的文献（医药）

2026-08-01·EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Discovery of APO-50815, a potent WEE1 kinase inhibitor with exceptional efficacy against patient-derived colorectal cancer organoids

Article

作者: Knapp, Stefan ; Barratt, Kate R ; Hasan, Sadia T ; Mukherjee, Siddhartha ; Thomson, Sophie F ; Wright, Josephine A ; Sloan, Erica K ; Priebbenow, Daniel L ; Chang, Aeson ; Baell, Jonathan B ; Kumar, Adarsh ; Syphers, Joel L ; Woods, Susan L ; Worthley, Daniel L ; Leeflang, Julia ; Gee, Yi Sing ; Vrbanac, Laura ; de Nys, Rebekah ; Krämer, Andreas ; Silva, Tharindie N ; Stockton, Kieran ; Lenz, Christopher ; Young, Savannah

Herein, we report the discovery of APO-50815 (14), a potent and selective thietane-3-ol WEE1 inhibitor. When tested against TP53-mutated colorectal cancer (CRC) patient-derived organoids (PDOs) grown from peritoneal and liver metastases, 14 exhibited outstanding anticancer efficacy, surpassing previously reported branched alkane counterpart 3, as well as clinical candidates AZD1775 (1) and ZN-c3 (2). Against primary CRC organoids with diverse TP53, BRAF and KRAS mutation profiles compared with patient-matched normal colon organoids, 14 exhibited selectively potent activity, yielding exceptionally high TI values (129-238) that highlight a substantial therapeutic window for potential cancer treatment. Against primary CRC PDOs (TP53-WT, BRAF-V600E, KRAS-WT), 14 profoundly elevated DNA damage and replication stress compared to 1, while amplifying cellular apoptosis, confirming a broadly similar but superior mode of action. Owing to its highly selective and exemplary anticancer efficacy, 14 represents a valuable tool compound for drug testing investigations against primary and metastatic CRCs, especially in the context of PDOs.

2026-07-01·iScience

The WEE1 inhibitor azenosertib broadly enhances efficacy of antibody-drug conjugates with topoisomerase I and microtubule inhibitor payloads

Article

作者: Chung, Heekyung ; Guo, Xiao ; Meric-Bernstam, Funda ; Cabrera, Erika ; Lackner, Mark R ; Harismendy, Olivier ; Lee, Catherine ; Kim, Doris ; Ma, Jianhui

Antibody-drug conjugates (ADCs) have transformed targeted cancer therapy, yet strategies to overcome resistance and enhance efficacy remain needed. Since ADCs exert anti-tumor effects via DNA damage or mitotic disruption, combining them with WEE1 inhibitors represents a rational approach. We investigated the selective WEE1 inhibitor azenosertib in combination with ADCs carrying topoisomerase I inhibitor (TOP1i) or microtubule inhibitor (MTI) payloads. Azenosertib enhanced the activity of free TOP1i agents and TOP1i-based ADCs (trastuzumab deruxtecan [T-DXd] and sacituzumab govitecan), increasing DNA damage and apoptosis, and extended the duration of response while overcoming T-DXd resistance in patient-derived xenografts. Synergistic effects were also observed with MTI agents and MTI-based ADCs (mirvetuximab soravtansine, tisotumab vedotin, and enfortumab vedotin), associated with exacerbated mitotic defects and prolonged mitotic arrest. All combinations enhanced efficacy and were well tolerated in vivo. These findings position azenosertib as a broadly applicable enhancer of cytotoxic-payload ADCs, offering a promising strategy for patients with advanced solid tumors.

2025-08-01·MOLECULAR CANCER THERAPEUTICS

Azenosertib Is a Potent and Selective WEE1 Kinase Inhibitor with Broad Antitumor Activity Across a Range of Solid Tumors

Article

作者: Rutgard, Michael ; Harismendy, Olivier ; Recio-Boiles, Alejandro ; Ma, Jianhui ; Lackner, Mark R. ; Grant, Stephan K. ; Levy, Alexandra ; Li, Jiali ; Cai, Zhen ; Kim, Daehwan ; Liu, Wen ; Sen, Shiraj ; Bunker, Kevin D. ; Segar, Jennifer M. ; Doroshow, Deborah B. ; Fischer, Kimberlee M. ; Kim, Sangyub ; Samatar, Ahmed A. ; Jandial, Danielle

Abstract:

Genomic instability and accumulation of DNA damage are hallmarks of tumor development and progression. To ensure the maintenance of genomic integrity, cells rely on a coordinated DNA damage response network that regulates cell-cycle progression, including activation of WEE1-dependent cell cycle checkpoints. If DNA damage occurs during replication, the WEE1 checkpoint is activated, thereby preventing the progression of the cell cycle. This allows damaged DNA to be repaired before cells enter mitosis, or if the damage is too extensive, induction of apoptosis. These observations have made WEE1 a promising anticancer therapeutic target. Azenosertib (ZN-c3) is a novel, selective, and orally bioavailable WEE1 inhibitor. The antiproliferative activity of azenosertib on cancer cell lines is consistent with a WEE1-dependent mechanism of action exemplified by reduction of pY15-CDK1 levels and increases in DNA damage markers. Azenosertib further exacerbates the effect of replicative stress and DNA damage by allowing cancer cells to prematurely enter mitosis, leading to mitotic catastrophe and apoptosis. Azenosertib has optimized pharmacokinetic and pharmacodynamic properties, yielding robust tumor growth inhibition in a broad range of tumor models, and is highly effective at delaying the duration of tumor regrowth after cessation of treatment. We have explored various dosing schedules in preclinical efficacy models for azenosertib that preserve antitumor activity with minimal toxicity. Phase I studies with azenosertib as monotherapy have shown preliminary clinical activity in patients with advanced solid tumors. The data presented herein support further studies of azenosertib monotherapy across multiple solid tumor indications.

161

项与 Azenosertib 相关的新闻（医药）

2026-06-29

·BioSpace

4 ovarian cancer candidates to watch: GSK, Allarity and more

iStock, valiantsin suprunovich Recent approvals for Corcept Therapeutics and Merck have injected momentum into the space, where GSK, Allarity Therapeutics, OSE Immunotherapies and others are advancing their own candidates. The market for drugs designed to treat the deadliest gynecological malignancy—ovarian cancer—is gaining steam, thanks to two recent approvals and a crop of novel candidates in earlier-stage trials. In February, Merck secured an FDA approval for Keytruda and subcutaneous injection Keytruda Qlex with paclitaxel for patients with platinum-resistant ovarian cancers (PROC). The addition of the blockbuster immunotherapy led to a 24% reduction in the risk of death, according to Phase 3 trial data. The agency then approved Corcept Therapeutics’ glucocorticoid blocker Lifyorli in PROC in March, with recent data showing a 35% reduction in the risk of death in combination with nab-paclitaxel compared to chemotherapy alone. Both approvals were huge wins, particularly for platinum-resistant ovarian cancer, where treatment options are limited, said Premal Thaker, the WashU Medicine director of gynecological oncology clinical research at Siteman Cancer Center . Thaker is the principal investigator on the Phase 3 OVATION-3 trial, which is evaluating a gene therapy from Imunon called IMNN-001 that is designed to boost levels of IL-12 and change the tumor microenvironment, alongside chemotherapy. Phase 2 data reported in March showed a 14.7-month increase in overall survival compared to standard of care chemotherapy. IMNN-001 is one of several candidates bringing new interest to a stubborn disease with a relative 5-year survival rate of 52% and limited treatment options. “A lot of drugs have gone into trials for many, many decades, and we just haven’t had the same success that we’re seeing right now,” Thaker told BioSpace . “It’s smarter drugs and medications.” Here are four candidates, each with a different mechanism of action, that the field is watching. Make way for GSK’s Mo-Rez and the ADCs The biggest frontrunners poised to make a dent in ovarian cancer are antibody-drug conjugates (ADCs), where AbbVie’s folate receptor antagonist Elahere is first-in-class . Another candidate with recent data is GSK’s mocertatug rezetecan, or Mo-Rez, a novel ADC that targets an antigen called B7-H4 and carries a topoisomerase inhibitor payload. In its Phase 1 dose-escalation trial, BEHOLD-1, Mo-Rez had a confirmed objective response rate (cORR) of 62% in patients with PROC and 67% in those with endometrial cancer, according to data presented at the Society for Gynecological Oncology’s annual meeting in April. “We were pretty happy with that,” Eric Richards, senior vice president and head of medicine development leaders for oncology at GSK, told BioSpace . “What we’re seeing is not only a high level of clinical activity but initial signs of pretty good durability.” Richards added that the immune checkpoint protein B7-H4 is overexpressed in the vast majority of ovarian cancer cells, making it an attractive target. GSK is launching five Phase 3 trials evaluating Mo-Rez this year across ovarian and endometrial cancers, including BEHOLD-Ovarian01 in PROC and BEHOLD-Ovarian02 in platinum-sensitive ovarian cancer. Elsewhere, German biotech Tubulis, recently acquired by Gilead, also recently reported positive results from a Phase 1 trial evaluating its ADC, TUB-040, in PROC. And Daiichi Sankyo and Merck are progressing their candidate raludotatug deruxtecan (R-Dxd) in a Phase 2/3 trial. It’s too early to say which candidates look most promising, Thaker said, adding that many of them carry the same topoisomerase payload. Their side effects will likely be a differentiating factor, she said. “It’s a little bit of a scientific conundrum right now—how are we going to sequence these? Because they all look very exciting.” Cancer ASCO: A battle of bispecifics, Eli Lilly’s big win and more Practice-changing data in lung cancer, prostate cancer and more were on display over the weekend at the American Society of Clinical Oncology annual meeting in Chicago. Plus, early readouts on assets that could reshape the cancer landscape. June 1, 2026 · 4 min read · Brianna Abbott Read more Zentalis chases a new target in WEE1 Zentalis Pharmaceuticals, meanwhile, is enrolling a Phase 3 global trial evaluating its novel inhibitor azenosertib in patients with cyclin E1–positive PROC against standard single-agent chemotherapy, according to a May press release . Azenosertib is designed to inhibit the protein kinase WEE1, a master regulator of cell cycle checkpoints. At the 2026 American Society of Clinical Oncology annual meeting, data from the Phase 1b MUIR trial showed that azenosertib plus paclitaxel resulted in an ORR of 39% and a median progression-free survival (PFS) of 7.3 months in an all-comer PROC population. Both the cyclin E1-positive and negative groups had similar responses, the trial found. The FDA granted Fast Track designation to the drug in January 2025 for patients who are positive for the cyclin E1 protein, which is overexpressed in around half of PROC patients. Ovarian cancer tumors positive for cyclin E1 are often especially hard to treat, Thaker noted. “It’s nice that we’re developing a medication that can help overcome that,” Thaker—who is also involved in the research—said. Plus, she added, the azenosertib pill might be easier to take than some of the ADCs, which are delivered via infusions. OSE’s proof-of-concept for cancer vaccines More positive ovarian cancer data at ASCO 2026 came from OSE Immunotherapeutics, which reported Phase 2 results for its off-the-shelf vaccine Tedopi (OSE2101), designed to stimulate a patient’s T cells and target five different tumor-linked antigens. In the TEDOVA trial, some 185 patients with platinum-sensitive recurrent ovarian cancer (PSOC) were randomized to Tedopi, Tedopi plus pembrolizumab or best supportive care as maintenance treatment after chemo. Patients in the trial were also required to be HLA-A2 positive, which shrinks the number of potentially eligible patients, Thaker said. “We have to be mindful when we look at some of these targets, we have to cut the pie a little bit more.” With a median follow-up of 22 months, patients on Tedopi and pembrolizumab experienced a median PFS of 4.1 months, compared to 2.8 months for those getting the best supportive care. The addition of pembrolizumab to Tedopi led to a 28% reduction in the risk of progression or death, compared to Tedopi alone, the trial found, though that result missed the mark for statistical significance. The results are the first proof of concept for a therapeutic vaccine in ovarian cancer and the first positive trial for PSOC in years, Alexandra Leary, deputy head of the department of medical oncology at Gustave Roussy in France and lead investigator on the trial, said in a press release . Allarity’s next generation PARP inhibitor Allarity Therapeutics’ stenoparib is another candidate with FDA Fast Track designation. The drug is a dual-target inhibitor that homes in on PARP 1/2 and tankyrase 1/2, differentiating it from earlier PARP inhibitors such as AstraZeneca and Merck’s Lynparza and GSK’s Zejula. Inhibiting tankyrase can disrupt signaling in the WNT pathway, which has been implicated in multiple cancers, Jeremy R. Graff, president and chief developmental officer at Allarity, told BioSpace . “It really seems to be particularly highly activated in really advanced, chemo- and radio-resistant cancers.” Allarity licensed stenoparib in 2017 from Eisai based on the drug’s Phase 1 data. In Phase 2 data reported in September 2025, the median overall survival had not been reached at 25 months for patients with platinum-resistant and refractory ovarian cancer. The drug appeared to benefit patients regardless of their BRCA status, Graff added. The company is expanding its Phase 2 trial for patients with PROC and has amended its trial protocol to focus on advanced, recurrent, platinum-resistant or platinum-ineligible ovarian cancer. Like with Zentalis’s azenosertib, the pill will likely be easier to take with milder toxicities than the ADCs, Graff said, which could be particularly helpful for older women. Ovarian cancer hasn’t historically garnered as much attention as cancers with the biggest patient pools, including breast or prostate cancer, Graff said. But the hard-to-treat disease is now capturing more interest. “It’s a huge unmet medical need,” Graff said. “We’d love to, with the era of targeted therapies, go beyond just poisoning people with chemotherapy.” .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });

临床结果临床3期临床1期ASCO会议临床2期

2026-06-13

·LFS之家

WEE1抑制剂联合长春花生物碱可作为Li-Fraumeni综合征相关髓母细胞瘤的联合治疗方案

2026年2月发表在《iScience》杂志上的一篇文章《临床前药物筛选发现：WEE1抑制剂联合长春花生物碱可作为Li-Fraumeni综合征相关髓母细胞瘤的联合治疗方案》。研究要点药物筛选结果显示，阿达沃西布（WEE1激酶抑制剂）联合长春新碱对Li-Fraumeni综合征相关SHH型髓母细胞瘤抑瘤效果最优。患者基因表达特征提示，TP53突变型SHH髓母细胞瘤对阿达沃西布具有药物敏感性。动物实验证实，该联合用药方案在Li-Fraumeni综合征小鼠模型中毒性较低。敲低阿达沃西布的作用靶点WEE1，可抑制TP53突变型SHH髓母细胞瘤模型的肿瘤生长。摘要 Li-Fraumeni综合征（李-弗劳梅尼，LFS）以TP53胚系致病性突变为特征，患者恶性肿瘤发病风险显著升高，其中也包括SHH型髓母细胞瘤（SHH-MB）。对于LFS患者，放疗及DNA损伤类药物不仅疗效有限，还易诱发继发恶性肿瘤。为筛选出适用于LFS相关SHH型髓母细胞瘤的高效、安全化疗方案，本研究在TP53突变型脑肿瘤细胞系中对333种化合物开展体外药物筛选。结果显示，WEE1抑制剂阿达沃西布联合长春花生物碱类药物长春新碱的抑瘤活性最强，该结果也在TP53突变型SHH型髓母细胞瘤患者来源类器官模型中得到验证。研究分别利用LFS成纤维细胞（体外）与LFS小鼠模型（体内）证实，该组合用药基因毒性较低。尽管此方案在患者来源异种移植（PDX）动物模型中疗效欠佳，但在TP53突变型SHH型髓母细胞瘤的体外及体内模型中，敲低WEE1基因均可显著抑制肿瘤生长。综上，本研究证实WEE1是治疗LFS相关SHH型髓母细胞瘤的潜力靶点，提示WEE1抑制剂联合长春新碱有望成为新的化疗策略。引言 Li-Fraumeni综合征（LFS）是一类遗传性肿瘤易感综合征，全球发病率约为1/3000~1/10000。绝大多数患者存在TP53基因胚系突变，该基因编码一种关键的抑癌基因。Li-Fraumeni综合征患者的高发肿瘤主要包括肉瘤、乳腺癌、肾上腺皮质癌及脑部肿瘤。在儿童群体中，TP53突变型SHH型髓母细胞瘤（SHH-MB）是该综合征最常见的脑部合并肿瘤，此类患者整体预后极差。 Li-Fraumeni综合征患者的肿瘤治疗难题，不仅体现在肿瘤发病风险升高。目前针对该疾病已建立并推行了多套完善的筛查与监测方案，但针对LFS相关肿瘤，学界尚未形成统一的抗肿瘤治疗策略。传统抗肿瘤方案多采用化疗与放疗，二者均会造成DNA损伤；大量持续的DNA链断裂通常可诱导细胞凋亡。由于LFS患者本身存在DNA损伤应答机制缺陷，因此对这类常规治疗普遍应答不佳。此外，多项研究证实，DNA损伤类药物与LFS患者继发恶性肿瘤的发生存在明确因果关联。因此，临床上亟需研发对LFS相关肿瘤有效、且对正常组织低毒的新型疗法。联合用药相比单药治疗优势更为突出：两种及以上药物联用可通过靶向多条信号通路提升疗效，降低交叉耐药风险，同时还能克服肿瘤内部及肿瘤间的异质性问题。本研究旨在筛选可有效抑制LFS相关髓母细胞瘤细胞活性、且不会对正常组织造成基因毒性损伤的药物。研究首先利用两种TP53突变型脑肿瘤细胞系及正常LFS成纤维细胞，对大容量药物库开展体外筛选；随后在TP53突变型SHH型髓母细胞瘤患者来源异种移植（PDX）模型与LFS小鼠体内模型中验证药效。本研究发现的新型化疗方案，有望丰富LFS相关SHH型髓母细胞瘤的治疗选择，并为后续临床试验改善患者预后提供依据。结果体外药物筛选在Li-Fraumeni综合征相关脑肿瘤细胞系中筛选出多种有效药物类别本研究开展高通量药物筛选，旨在筛选疗效确切且毒性较低的联合用药方案。筛选药物库共包含333种化合物，作用靶点覆盖61种人体蛋白。其中激酶抑制剂占比最高，达56.8%；其余依次为传统化疗药物（15.6%）、雷帕霉素类似物（5.1%）、分化调控剂/表观遗传调节剂（9.9%）、凋亡调节剂（6.6%）、代谢调节剂（1.5%）及其他类药物（4.5%）。截至2025年，库中79%的化合物已获批上市或处于临床试验阶段。研究选取两株TP53突变型脑肿瘤细胞系开展单浓度梯度、单次重复单药筛选，分别为SJGBM-2（TP53p.R273C）与UW228-2（TP53p.T155N）。本研究采用药物敏感度评分3（DSS₃）作为药效评价指标，将两株细胞的DSS₃均≥20判定为有效候选药物。依据该标准，共筛选得到66种活性化合物。对比两株细胞的筛选结果可见，UW228-2细胞整体药物敏感性显著低于SJGBM-2细胞（中位DSS₃分别为9.5、1.3，威尔科克森检验：p＜0.05）。传统化疗药物、激酶抑制剂、分化/表观遗传调节剂、凋亡调节剂这几类药物，在两株细胞中的DSS₃差异均具有统计学意义。针对具体药物靶点分析：PI3K、AKT、DNA-PK抑制剂对UW228-2细胞的抑瘤效果更强；而E3连接酶、极光激酶、周期蛋白依赖性激酶（CDK）抑制剂则对SJGBM-2细胞作用更显著，两类靶点对应的药物在两株细胞间的中位DSS₃差异最为突出。激酶抑制剂与微管相关化合物对体外培养的Li-Fraumeni综合征正常细胞毒性及基因毒性微弱将上述66种高活性化合物，采用与肿瘤细胞相同的实验条件，作用于Li-Fraumeni综合征正常成纤维细胞。筛选标准设定为：正常细胞的药物敏感度评分（DSS₃）≤10，且肿瘤细胞与正常细胞的DSS₃差值（dDSS₃）＞20。据此筛选出24种对正常细胞无明显细胞毒性的化合物。其中4种化合物（克拉屈滨、氟尿苷、硫唑嘌呤、甲氨蝶呤）因已有研究证实，其在LFS体外及体内模型中可造成DNA损伤，故予以剔除。最终保留20种化合物开展基因毒性检测。本研究采用微核试验开展基因毒性筛选，检测药物处理后LFS成纤维细胞的微核形成情况。以丝裂霉素C作为阳性对照，若化合物检测结果与阳性对照存在统计学差异（p＜0.05），则判定为无基因毒性。20种化合物中，共有11种未表现出基因毒性。对于微管相关化合物，其引发的微核现象无法区分是源于染色体断裂，还是该类药物固有作用机制——即结合微管蛋白、造成有丝分裂纺锤体功能异常所致。但结合既往研究，这类药物不会在TP53突变细胞中诱发可致肿瘤发生的显著DNA损伤，因此这3种微管相关化合物仍纳入后续研究。剩余14种候选药物，在两株TP53突变脑肿瘤细胞系（SJGBM-2、UW228-2）及LFS成纤维细胞中，扩大药物浓度范围（0.1~10000纳摩尔）并设置三组重复实验进行复筛。将肿瘤细胞中最大药效（Eₘₐₓ）不足50%的化合物剔除。最终共得到8种药效达标化合物：2种ATM/ATR抑制剂（AZD6738、BAY-1895344）、2种CHK1/2抑制剂（PF-477736、AZD7762）、WEE1抑制剂（阿达沃西布），以及3种微管相关药物（来立布林、紫杉醇、长春新碱）。 WEE1抑制剂阿达沃西布联合长春新碱可降低体外LFS相关脑肿瘤细胞的活性本研究在两株脑肿瘤细胞系（SJ-GBM2、UW228-2）中，对筛选得到的候选化合物（5种激酶抑制剂、2种微管相关药物）开展联合用药评价。由于来立布林、紫杉醇在儿童脑肿瘤临床中应用有限，本联合筛选改用髓母细胞瘤常规治疗药物长春碱（长春花生物碱类）替代上述两种微管药物。 ATM、ATR、CHK1、CHK2及WEE1抑制剂作用于同一细胞周期检查点通路，因此彼此间不进行联用。根据协同评分结果，长春碱、长春新碱分别与各类激酶抑制剂联用均表现为相加效应，未出现拮抗作用。综合排名显示，阿达沃西布+长春新碱、BAY-1895344+长春新碱两组联用方案抑瘤效果最优。两种药物在LFS相关SHH型髓母细胞瘤细胞（UW228-2）与正常对照LFS成纤维细胞中的作用特征相近：阿达沃西布、BAY-1895344作用于UW228-2细胞的药物敏感度评分分别为10.4、12.8，而二者对LFS成纤维细胞的药物敏感度评分均为0。为提升研究的临床参考价值，本研究梳理了两种药物的临床试验数据及血肿瘤屏障穿透能力相关报道（数据统计截止至2023年5月26日）：阿达沃西布相关临床试验共61项，其中纳入儿童患者的试验5项；BAY-1895344相关临床试验共9项，仅1项纳入儿童患者。药物瘤内浓度数据显示，胶质母细胞瘤患者瘤内阿达沃西布浓度可达858纳摩尔，小鼠模型中BAY-1895344瘤内浓度为495纳摩尔。综合以上信息判断，相较于BAY-1895344，阿达沃西布更适合快速应用于LFS相关SHH型髓母细胞瘤的联合治疗。因此后续所有实验均选用阿达沃西布作为联用药物。阿达沃西布的直接作用靶点为WEE1激酶，该蛋白负责调控G2/M期细胞周期检查点转换。在TP53功能缺失的肿瘤细胞中，抑制WEE1会造成DNA损伤持续累积、复制应激加剧，最终引发有丝分裂崩溃。蛋白检测结果证实，两株细胞经阿达沃西布处理后，CDK1磷酸化水平下降，提示该药物可有效作用于目标靶点。 TP53突变型SHH髓母细胞瘤的生长依赖WEE1激酶活性为证实TP53突变脑肿瘤细胞的生长依赖WEE1活性，本研究在SJGBM-2、UW228-2两株细胞中对内源性WEE1蛋白进行基因敲低。借助小干扰RNA实现WEE1敲低后，实验组细胞增殖能力较对照组显著下降：SJ-GBM2细胞平均活性降至25.5%（p＜0.05），UW228-2细胞平均活性降至70.3%（p＜0.01）。在UW228-2细胞中，低浓度长春新碱（0.5纳摩尔）联合WEE1敲低的抑瘤效果显著优于单药处理：单用长春新碱组细胞平均活性为80.2%，联合组为61.8%；联合组与单药组、单纯敲低组相比差异均有统计学意义（分别为p＜0.001、p＜0.01）。在SJ-GBM2细胞中，仅联合用药组与单用长春新碱组的细胞活性存在显著差异（单用长春新碱：62.9%，联合组：16.2%，p＜0.01），单纯WEE1敲低组与联合组相比无统计学差异（p＞0.05）。两株细胞的布利斯协同评分分别为−0.2、−5.14，提示该联用方案在两种细胞中均表现为相加效应。敲低WEE1可显著激活SJ-GBM2与UW228-2细胞内半胱天冬酶-3。长春新碱单药对半胱天冬酶-3活性无明显影响，这也符合该药物在TP53突变肿瘤细胞中以抑制增殖为主、而非直接杀伤细胞的作用特点；同时长春新碱不会削弱WEE1敲低所诱导的促凋亡效应。本研究另外选取两种WEE1抑制剂（Debio0123、ZN-c3）在TP53突变脑肿瘤细胞中开展药效验证，其作用强度与阿达沃西布相近。半数抑制浓度数据如下：SJ-GBM2细胞中，阿达沃西布43.4nM、Debio0123147.1nM、ZN-c369.7nM；UW228-2细胞中，阿达沃西布272.7nM、Debio0123270.5nM、ZN-c3271.1nM。与阿达沃西布一致，这两种药物分别联合长春新碱使用时，也均呈现相加作用。利用TP53突变型SHH髓母细胞瘤患者来源类器官完成候选药物验证为提升研究结果的临床参考价值，本研究进一步在TP53突变型SHH髓母细胞瘤患者来源类器官（PDO）模型中，验证阿达沃西布联合长春新碱的作用效果。受试的3种类器官模型均显示两药联用为相加效应，未出现拮抗作用，协同评分区间为−6.35~2.52，与传统细胞系实验结论一致。单药药效对比结果显示：长春新碱降低类器官代谢活性的作用有所减弱，其半数抑制浓度均值为6.8nM（范围1.38~11.9nM），而该药物在传统细胞系SJ-GBM2、UW228-2中的半数抑制浓度分别仅为1.1nM、0.9nM。阿达沃西布在类器官模型中的半数抑制浓度均值为166.5nM（范围117.4~215.3nM），高于SJ-GBM2细胞（43.4nM）、低于UW228-2细胞（272.7nM）。两种药物的作用均高度依赖细胞周期，这类药效差异在二维传代细胞系与三维类器官对比实验中十分常见：类器官的增殖与细胞周期运转速度更慢、基因表达模式存在差异，且药物难以穿透三维结构，最终导致离体培养的类器官对药物敏感性下降。其中SJ-GBM2细胞对药物的敏感度更是达到类器官的3~8倍。综上，在全部3种TP53突变型SHH髓母细胞瘤患者来源类器官模型中，均证实阿达沃西布与长春新碱联用可产生相加作用，有效抑制细胞代谢活性。相较于其他儿童脑部肿瘤，SHH型髓母细胞瘤的WEE1表达水平与阿达沃西布敏感评分更高本研究依托已发表的儿童原发性脑部肿瘤数据集，分析药物靶点及预测性生物标志物的表达特征。对Roth与Northcott队列的mRNA表达数据进行分析后发现：髓母细胞瘤组织中WEE1的mRNA表达水平显著高于正常小脑组织；在各亚型髓母细胞瘤里，SHH型髓母细胞瘤的WEE1表达量最高（p＜0.01）。在SHH型髓母细胞瘤内部，SHH-α亚型（SHH_3，包含LFS相关髓母细胞瘤病例）、SHH-β亚型（SHH_1）及SHH-δ亚型（SHH_4）的WEE1 mRNA表达水平位居前列。既往研究显示，在不同肿瘤类型中，WEE1表达量与细胞对阿达沃西布的敏感性并无明确关联。因此本研究采用一套经验证的儿童肿瘤阿达沃西布敏感性特征谱开展深度分析。结果显示，原发性髓母细胞瘤的阿达沃西布敏感评分（AdSS）显著高于多数儿童脑部肿瘤（p＜0.01），仅与非典型畸胎样/横纹肌样瘤（ATRT）相近（差异无统计学意义）。各髓母细胞瘤亚型对比：SHH型的阿达沃西布敏感评分与WNT亚型、第3组亚型无明显差异，但显著高于第4组亚型（p＜0.001）；而包含LFS相关髓母细胞瘤的SHH-α（SHH_3）亚型，在所有SHH亚型中敏感评分最高（p＜0.01）。单独的TP53突变状态与髓母细胞瘤的药物敏感评分无相关性，这也与阿达沃西布相关临床试验结论相符，即TP53突变不能作为预测该药物疗效的生物标志物。体内实验证实：抑制WEE1活性可阻碍TP53突变型SHH髓母细胞瘤患者来源异种移植模型的肿瘤生长本研究采用阿达沃西布联合长春新碱，对LFS相关SHH髓母细胞瘤DKFZ-BT084患者来源异种移植（PDX）模型开展体内给药实验。结果显示，该方案对肿瘤生长及荷瘤动物生存期均无显著影响（对数秩检验：p＞0.05）。各组荷瘤小鼠自检出肿瘤后的中位生存期分别为：对照组17.5天、阿达沃西布单药组9天、长春新碱单药组20.5天、联合用药组28天。为验证阿达沃西布在体内是否发挥靶点作用，本研究在另外两株LFS相关SHH髓母细胞瘤PDX模型中检测CDK1磷酸化水平。结果显示，阿达沃西布联合长春新碱处理组与对照组的磷酸化CDK1表达量无明显差异，提示该药物在体内未有效作用于目标靶点。推测原因可能为药物血脑屏障穿透能力不足，这也是其体内药效不佳的主要诱因。为进一步验证肿瘤在体内的生长依赖WEE1活性，本研究利用短发夹RNA（shRNA）稳定敲低LFS原发SHH髓母细胞瘤PDX模型细胞的WEE1基因，观察肿瘤形成与生长特征。WEE1敲低组共5只小鼠，其中3只（60%）长出肿瘤；转染乱序对照shRNA的对照组5只小鼠全部（100%）成瘤（费希尔精确检验：p=0.44）。两组动物生存期存在显著差异：观察期内对照组5只小鼠均因肿瘤进展死亡，而WEE1敲低组仍有2只存活（p=0.044）。阿达沃西布联合长春新碱在LFS小鼠模型中未见明显毒性反应本研究初筛药物时，已将基因毒性作为核心筛选标准，旨在为DNA损伤易感的LFS患者筛选低毒药物。本研究采用Trp53+/-LFS小鼠模型（品系：Trp53tm1Tyj/J），评估阿达沃西布与长春新碱的体内毒性。在给药及观察期间，实验动物未出现不良反应，体重保持稳定。对照组、单药组及联合用药组动物存活率均为100%。动物解剖结果显示，各脏器均未出现提示肿瘤发生的肉眼病变；对脑、肾、肝、脾组织开展组织学检测，也未发现异常。各组脏器中γH2AX阳性细胞核数量无统计学差异。上述结果证实：在Trp53缺陷型小鼠模型中，单用或联用长春新碱、阿达沃西布，均基本无基因毒性及脏器毒性。讨论本研究对333种化合物开展筛选，旨在探索Li-Fraumeni综合征相关髓母细胞瘤的新型治疗方案。最终确定WEE1抑制剂阿达沃西布联合长春花生物碱类药物长春新碱为疗效佳且毒性低的最优组合。两种药物在Li-Fraumeni综合征体外、体内模型中均无基因毒性，联用后对肿瘤细胞表现为相加作用。尽管该药物组合在动物体内给药实验中未显现明显疗效，但在患者来源异种移植（PDX）模型中对WEE1进行基因敲低后，肿瘤生长受到抑制，免疫缺陷小鼠生存期也得以延长，证实WEE1是治疗Li-Fraumeni综合征相关SHH型髓母细胞瘤的潜力靶点。值得注意的是，该联用方案的作用并不局限于TP53突变型SHH髓母细胞瘤：TP53突变肿瘤对其敏感，TP53野生型肿瘤同样可能产生应答。由于阿达沃西布与长春新碱基本无基因毒性，后续也可探索该方案用于治疗其他类型的Li-Fraumeni综合征相关肿瘤。本研究证实，无论体外还是体内实验，TP53突变型SHH髓母细胞瘤的生长均依赖WEE1活性。从作用机制来看，TP53突变会造成G1/S细胞周期检查点调控功能缺陷，这也是Li-Fraumeni综合征肿瘤细胞对传统化疗耐药的重要原因。与此同时，细胞分裂异常加快，使得肿瘤细胞必须依靠G2/M检查点完成DNA损伤修复，才能顺利进入分裂期。阿达沃西布靶向调控G2/M期转换的WEE1激酶，会迫使细胞提前进入分裂阶段，进而加剧基因组不稳定性，最终诱发有丝分裂崩溃。因此多项研究认为，TP53突变可作为预判阿达沃西布疗效的潜在生物标志物，但成人临床试验却得出了相互矛盾的结论。目前临床主流治疗方案以传统化疗为主，难以实现Li-Fraumeni综合征相关SHH型髓母细胞瘤患者的长期无进展生存，该类患者5年无进展生存率仅为20%。长春新碱已是这类肿瘤的常规治疗用药；阿达沃西布则正开展儿童恶性脑肿瘤的早期临床试验（试验编号：NCT02095132）。截至目前，尚无证据表明WEE1抑制剂能让髓母细胞瘤患者显著获益，且专门针对TP53突变型SHH髓母细胞瘤的临床数据仍处于空白状态。多项研究表明，WEE1是髓母细胞瘤极具开发价值的药物靶点。Keller等人2022年发表的系统性综述指出，WEE1抑制剂及其他细胞周期激酶抑制剂，无论单药还是联合放化疗，都是治疗髓母细胞瘤最具前景的药物。Harris团队通过整合基因组分析，同样证实WEE1是髓母细胞瘤中可靶向的有效靶点。血脑屏障是限制脑部肿瘤药物疗效的关键因素。已有研究报道了阿达沃西布的体内血脑屏障穿透能力：Pokorny团队发现，在原位胶质母细胞瘤PDX模型中，药物在肿瘤组织内分布不均，瘤内药物浓度仅为血药浓度的5%，穿透效果较差，这一结果也与两项成人胶质母细胞瘤Ⅰ期临床试验（NCT01849146）结论相符。但另一项胶质母细胞瘤患者药代动力学研究显示，单次口服给药后，阿达沃西布血脑屏障穿透性良好，肿瘤内游离药物浓度与血浆药物浓度中位比值达3.2。两种结果存在差异的原因在于：胶质母细胞瘤的血管存在窗孔样结构，而SHH型髓母细胞瘤的血脑屏障结构完整。结合阿达沃西布本身穿透血脑屏障能力有限这一特点，也解释了为何该药物难以在SHH型髓母细胞瘤治疗中发挥作用。脑部肿瘤体内模型实验显示，阿达沃西布单药或联合化疗，可有效抑制皮下接种的脑肿瘤细胞生长，但在颅内原位接种模型中的疗效却参差不齐。Pokorny与Moreira的研究均证实，原位模型对药物的敏感性显著低于异位皮下模型，进一步说明血脑屏障通透性会直接影响阿达沃西布的体内药代特征，导致肿瘤部位药物浓度不足。加之SHH型髓母细胞瘤PDX模型的血脑屏障结构本身存在变异，也让相关实验结果的解读更为复杂。本研究已明确WEE1具备成药价值，因此后续研究重心应放在研发高血脑屏障穿透性的WEE1抑制剂。目前已有多款候选药物进入临床阶段，如ZN-c3（NCT04158336）、Debio0123（NCT03968653）。本实验证实，二者在TP53突变脑肿瘤模型中的药效与阿达沃西布相当；另有研究显示，Debio0123在胶质母细胞瘤原位模型中疗效确切，且可有效穿透血脑屏障。此外，新型药物递送技术也在持续探索中，包括纳米颗粒、聚合物胶束等载体系统。目前正在胶质瘤中开展临床评估的微泡联合聚焦超声无创技术，也有望提升WEE1抑制剂的血脑屏障穿透效率。若能筛选出Li-Fraumeni综合征特异性的阿达沃西布疗效预测标志物，也可进一步挖掘该药物的应用潜力，但这类研究受限于该病相关SHH型髓母细胞瘤患者样本稀少，推进难度较大。对于肿瘤易感综合征患者，新型疗法的基因毒性是必须考量的核心问题。采用DNA损伤类药物治疗Li-Fraumeni综合征患者，会大幅提升继发肿瘤风险，因此本研究重点评估了候选药物引发DNA双链断裂及持续性DNA损伤的能力。阿达沃西布兼具放化疗增敏作用，但既往临床试验尚未明确其单用是否会造成DNA损伤。本研究发现，Li-Fraumeni综合征正常细胞经阿达沃西布长期处理后，γH2AX病灶与微核形成数量并未增加。长春新碱属于微管靶向药物，采用微核试验评估其基因毒性易出现结果偏差，但既往多项体内外实验均证实，长春花生物碱不会在Li-Fraumeni综合征模型中造成明显DNA损伤、诱发肿瘤。同时，在Trp53缺陷型Li-Fraumeni综合征小鼠模型中，单用或联用两种药物均未观察到与基因缺陷相关的不良反应及脏器毒性。综上可以判定，阿达沃西布联合长春新碱可安全应用于Li-Fraumeni综合征患者。本类临床前研究也存在局限性，实验模型的选择会影响研究结果向临床转化的价值。目前成熟、能够精准模拟TP53突变型SHH髓母细胞瘤的体外模型数量十分有限。现阶段针对SHH型髓母细胞瘤的靶向治疗探索整体进展缓慢：Pak团队发现，组蛋白去乙酰化酶抑制剂可与药物抵抗型髓母细胞瘤形成有效联用方案，但该结论仍需临床试验验证；Endersby团队证实CHK1抑制剂对第3组髓母细胞瘤有效，却对TP53突变型SHH髓母细胞瘤PDX模型无效；Simovic团队发现碳离子放疗对Li-Fraumeni综合征相关SHH髓母细胞瘤疗效显著，但联合聚腺苷二磷酸核糖聚合酶抑制剂后并未进一步提升效果。本中心的临床数据也证实，放疗能够延长这类患者的生存期，具备明确临床价值。针对其他Li-Fraumeni综合征相关脑部肿瘤，Reed团队依托转录组测序精准医疗平台，发现1例Li-Fraumeni综合征胶质母细胞瘤患者存在STAT1/STAT2高表达，对芦可替尼敏感，据此制定个体化方案后，患者病情得到有效控制。当前新药研发常借助患者来源模型开展药物筛选，以此挖掘针对单个患者或小众患者群体的驱动基因与靶向药物。在临床前研究中，基因编辑动物模型、患者来源异种移植模型等体内体系的药效验证至关重要。与此同时，类器官体外检测技术作为功能化精准医疗手段，也在多项临床试验中得到推广应用（NCT03896958、NCT03336931、NCT03133273）。总结：本研究通过药物筛选与多轮验证，确定WEE1抑制剂阿达沃西布联合长春新碱是治疗Li-Fraumeni综合征相关髓母细胞瘤的潜力组合，具备开展临床试验的价值。该方案对Li-Fraumeni综合征正常细胞基因毒性低，在相关肿瘤模型中抑瘤效果显著，且在基因编辑Li-Fraumeni综合征小鼠模型中证实安全性良好。尽管该组合在本研究的体内给药实验中未显现疗效，但结合靶点验证结果可知：若能解决药物血脑屏障穿透难题，WEE1抑制剂联合长春新碱可纳入Li-Fraumeni综合征相关SHH型髓母细胞瘤的治疗方案。后续需开展临床试验，验证高穿透性WEE1抑制剂联合长春新碱，在该类肿瘤以及其他Li-Fraumeni综合征相关肿瘤中的实际疗效。研究局限性本研究主要围绕筛选得到的长春新碱联合阿达沃西布组合，探索其作为Li-Fraumeni综合征相关SHH型髓母细胞瘤新型疗法的应用潜力。本次筛选所用药物库中的化合物，大多为已获批上市或处于临床研发阶段的药物。药物初筛仅采用两株TP53突变脑肿瘤细胞系开展实验，但后续已在三株可真实模拟该类肿瘤的TP53突变型SHH髓母细胞瘤患者来源类器官中完成候选药物验证。本研究另一项不足为：LFS小鼠模型体内毒性实验的观察周期较短（仅4周），无法评估药物长期毒性，例如治疗诱发的新发肿瘤。不过，实验未检测到DNA损伤标志物明显升高，提示该方案诱发治疗相关继发肿瘤的风险较低。最后，本研究采用的动物模型无法完全复刻LFS患者的各项特征，包括TP53突变谱、血脑屏障结构等，均与人体存在差异。原文：Kolodziejczak AS, Selt F, Peterziel H, et al. Preclinical drug screen identifies WEE1 inhibitor and vinca alkaloid as a combination treatment concept for Li-Fraumeni syndrome medulloblastoma. iScience. 2025 Dec 29;29(2):114564. doi: 10.1016/j.isci.2025.114564. PMID: 41585496; PMCID: PMC12828543. Li-Fraumeni综合征病友群（LFS之家）联系人：徐若木微信：Rome-Xu

2026-06-02

·BioSpace

Zentalis Pharmaceuticals Announces Inducement Grants Under Nasdaq Listing Rule 5635(c)(4) - June 1, 2026

SAN DIEGO, June 01, 2026 (GLOBE NEWSWIRE) -- Zentalis ® Pharmaceuticals, Inc. (Nasdaq: ZNTL), a clinical oncology innovator advancing late-stage development of investigational first-in-class WEE1 inhibitor azenosertib as a biomarker-driven treatment approach for ovarian cancer, today announced that on June 1, 2026, the Compensation Committee of Zentalis’ Board of Directors granted non-qualified stock options to purchase an aggregate of 191,000 shares of the Company’s common stock to two (2) newly hired employees. The stock options were granted under the Zentalis Pharmaceuticals, Inc. 2022 Employment Inducement Incentive Award Plan (2022 Inducement Plan) as an inducement material to each such individual’s entering into employment with Zentalis in accordance with Nasdaq Listing Rule 5635(c)(4). The 2022 Inducement Plan is used exclusively for the grant of equity awards to individuals who were not previously employees of Zentalis, or following a bona fide period of non-employment, as an inducement material to each such individual’s entering into employment with Zentalis, pursuant to Nasdaq Listing Rule 5635(c)(4). The stock options have an exercise price of $3.98 per share, which is equal to the closing price of Zentalis’ common stock on The Nasdaq Global Market on the date of grant. The stock options have a 10-year term and will vest over four years, with 25% of the options vesting on the first anniversary of the vesting commencement date and the remaining 75% of the options vesting in equal monthly installments over the three years thereafter. Vesting of the stock options is subject to the employee’s continued service to Zentalis on each vesting date. About Zentalis Pharmaceuticals Zentalis is a clinical oncology innovator developing a treatment approach for ovarian cancer and multiple tumor types. Leveraging therapeutics development and biomarker expertise, Zentalis is advancing monotherapy and combination studies of its investigational first-in-class WEE1 inhibitor, azenosertib. Focused on translating WEE1 science into clinical practice, we aim to equip physicians with a targeted, non-chemo, orally available medicine that enhances treatment experience, choice, and outcomes. Our mission: to unburden cancer patients with more convenience and care. For more information, please visit . Follow Zentalis on LinkedIn at . ZENTALIS ® and its associated logo are trademarks of Zentalis and/or its affiliates. All website addresses and other links in this press release are for information only and are not intended to be an active link or to incorporate any website or other information into this press release. Contact: Aron Feingold VP, Investor Relations & Corporate Communications ir@zentalis.com

100 项与 Azenosertib 相关的药物交易

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适应症	最高研发状态	国家/地区	公司	日期
铂耐药性输卵管癌	临床3期	美国	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	澳大利亚	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	比利时	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	加拿大	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	法国	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	德国	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	爱尔兰	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	意大利	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	波兰	K-Group Beta, Inc.	2026-04-17
铂耐药性输卵管癌	临床3期	韩国	K-Group Beta, Inc.	2026-04-17

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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


NCT04516447 (Zn-c3-002, ESGO2026)	临床1期	卵巢癌维持 Cyclin E1 positive	14	Azenosertib plus bevacizumab	鏇壓築顧衊願鹹網網鏇(糧簾鬱餘製選襯遞醖獵) = The majority of treatment-related adverse events were grade 1-2, with the most common being paronychia (57.1%, all grade 1) and 夢憲遞窪淵淵膚鬱醖遞 (鹹願遞築製糧艱餘糧衊 ) 更多	积极	2026-02-28
NCT05743036 (Phase 1 dose escalation results of the WEE1 inhibitor, ASCO2025)	临床1期	转移性结直肠癌 BRAF V600E	44	Azenosertib	壓遞襯鹹顧製觸鑰鏇憲(鏇鹽艱願築鏇繭鬱艱蓋) = 11.4% 鏇網鏇繭壓製願衊齋鬱 (網築顧繭獵壓鹹襯選淵 ) 更多	积极	2025-05-30
NCT05198804 \| NCT05128825 \| NCT04158336 (AACR2025)	N/A	卵巢浆液性肿瘤 TP53 mutations	139	Azenosertib 300mg QD	鹽網窪廠網顧艱鹽築繭(醖窪顧蓋構齋蓋鹹獵艱) = 構遞製鏇醖淵膚壓膚鬱憲獵淵齋積繭醖鏇蓋範 (遞糧遞壓繭鹽淵獵獵網 ) 更多	积极	2025-04-28
NCT05198804 \| NCT05128825 \| NCT04158336 (AACR2025)	N/A	卵巢浆液性肿瘤 TP53 mutations	139	Placebo	鹽網窪廠網顧艱鹽築繭(醖窪顧蓋構齋蓋鹹獵艱) = 觸壓鬱蓋觸醖繭鏇蓋築憲獵淵齋積繭醖鏇蓋範 (遞糧遞壓繭鹽淵獵獵網 ) 更多	积极	2025-04-28
NCT05128825 (DENALI, Company_Website) 人工标引	临床2期	铂耐药性卵巢癌 CCNE1 Amplification	102	Azenosertib 400mg QD 5:2 dose	築簾夢衊膚衊選壓構願(繭夢網糧願廠觸糧壓範) = 廠壓鹹淵壓遞遞觸願艱夢襯鹽蓋醖願製鹽築製 (蓋衊壓獵願觸範鹹製憲, 21.0 ~ 50.9) 更多	积极	2025-03-15
NCT04833582 (ASCO2024)	临床1期	复发性骨肉瘤	31	Azenosertib	蓋範廠夢獵遞鏇遞膚觸(構鏇獵淵餘鏇壓築簾襯) = 積鏇鑰窪鹽獵襯簾窪鹹築艱齋廠糧獵鬱憲鬱鏇 (網鬱網餘糧鬱憲壓鹽製 )	积极	2024-05-24
NCT04516447 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	原发性腹膜癌 \| 卵巢上皮癌 \| 输卵管癌	94	Paclitaxel+Azenosertib	襯製選鏇壓製網醖憲顧(憲顧範構襯製選醖範鹽) = neutropenia (44.4), thrombocytopenia (30.3), anemia (12.1), leukopenia (11.1), fatigue (10.1), diarrhea (6.1), nausea (5.1), and vomiting (5.1) 簾顧衊餘鹽選鏇窪鬱獵 (積淵餘醖蓋廠顧選製蓋 )	积极	2023-05-26
NCT04516447 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	原发性腹膜癌 \| 卵巢上皮癌 \| 输卵管癌	94	Carboplatin+Azenosertib		积极	2023-05-26
NCT04516447 (AACR2022) 人工标引	临床1期	卵巢癌 \| 原发性腹膜癌 \| 输卵管癌二线 \| 三线	41	total	廠鬱廠鹹蓋壓衊觸蓋鹹(範鬱醖鬱窪襯鏇淵鏇範) = nausea 7.3%, neutropenia 34.1%, thrombocytopenia 17.1%, anemia 9.8%, diarrhea 2.4%, fatigue 2.4%, vomiting 9.8%, leukopenia 7.3%, abdominal pain 7.3%, hypoalbuminemia 2.4%, alanine aminotransferase increased 7.3%, and hypomagnesemia 2.4% 製廠蓋觸鹹觸鑰築蓋餘 (簾蓋艱醖醖醖積積憲遞 ) 更多	积极	2022-06-15
NCT04516447 (AACR2022) 人工标引	临床1期	卵巢癌 \| 原发性腹膜癌 \| 输卵管癌二线 \| 三线	41	carboplatin+ZN-c3		积极	2022-06-15
NCT04158336 (ZN-c3-001, AACR2022) 人工标引	临床1期	子宫浆液性癌	12	ZN-c3	積鑰鹹製網繭選窪鑰獵(鏇壓網簾醖簾願觸繭鬱) = 醖衊衊範繭製願簾夢觸窪壓窪鹹鬱願鹽醖鑰窪 (簾齋餘襯顧積憲窪繭鬱 ) 更多	积极	2022-06-15
NCT04158336 (ZN-c3-001, AACR 12021 \| AACR 22021) 人工标引	临床1期	HR阳性/HER2低表达实体瘤	39	ZN-c3	鹹繭積衊夢夢構鬱艱築(憲選膚構膚醖範鏇築膚) = 憲繭鏇獵願構壓願願壓築蓋積鹹廠觸齋願鹽鬱 (構夢鏇壓範壓願壓壓膚 ) 更多	积极	2021-04-10