Pancreatic cancer is a deadly disease and will be the second leading cause of cancer related death behind lung cancer by 2030. Over 62,000 people are diagnosed each year in the United States with about 90% succumbing to the disease within 5 years. In the metastatic setting, NALIRIFOX, FOLFIRINOX and nab-paclitaxel-gemcitabine are standard treatment options in patients with good performance status (Eastern Cooperative Oncology Group [ECOG] 0/1). All three combinations have shown a survival advantage over previously standard gemcitabine-based therapy, with 11.1 months overall survival (OS) for NALIRIFOX/FOLFIRINOX and 8.7 months for nab-paclitaxel-gemcitabine versus 6.7 months for gemcitabine alone. There is an urgent need to improve treatment of patients with current and emerging therapeutic strategies.
KRAS is the most common oncogene mutated in pancreatic adenocarcinoma, and it is mutated in nearly all tumors. Mutant KRAS is essential for PDAC growth, where the constitutive activated RAS proteins contribute to tumorigenesis, treatment resistance, and metastases. Despite research and drug development efforts focused on KRAS, no effective RAS inhibitors have been approved for the treatment of pancreatic cancer with KRAS mutation. The poor prognosis of KRAS-mutated PDAC patients and the absence of KRAS-targeted therapies, highlight the urgency to develop novel therapies aimed at KRAS.
This study will investigate onvansertib (also known as PCM-075 and NMS-1286937) as the first PLK1-specific adenosine triphosphate competitive inhibitor administered by oral route to enter clinical trials with proven antitumor activity in different preclinical models.

开始日期2025-02-01

申办/合作机构

University of Kansas Medical Center

[+1]

NCT06398587

/ Withdrawn临床2期IIT

An Open-Label, Phase II Trial to Assess Efficacy and Safety of Onvansertib in Combination With Gemcitabine and Nab-Paclitaxel in Patients With Previously Untreated, Locally-Advanced or Unresectable Pancreatic Adenocarcinoma

This phase II trial studies how well onvansertib in combination with gemcitabine and nab-paclitaxel works in treating patients with pancreatic ductal carcinoma (PDAC) that has spread to nearby tissue or lymph nodes (locally advanced), that cannot be removed by surgery (unresectable), or that has spread from where it first started (primary site) to other places in the body (metastatic). Onvansertib is a small chemical molecule that binds and stops the function of of PLK1 in tumor cells. By attacking the PLK1 protein, onvansertib is thought to reduce tumor cells ability to replicate and grow; causing them to die. Chemotherapy drugs, such as gemcitabine and nab-paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving chemotherapy with onvansertib may kill more tumor cells in patients with locally-advanced, unresectable, or metastatic pancreatic ductal carcinoma.

开始日期2024-08-01

申办/合作机构

OHSU Knight Cancer Institute

[+1]

NCT06106308

/ Active, not recruiting临床2期

A Phase 2, Randomized, Open-label Study of Onvansertib in Combination With FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab Versus FOLFIRI and Bevacizumab or FOLFOX and Bevacizumab for First-line Treatment of Metastatic Colorectal Cancer in Patients With a KRAS or NRAS Mutation

The purpose of this study is to assess 2 different doses of onvansertib to select the lowest dose that is maximally effective, and to assess the safety, efficacy, pharmacokinetics, and pharmacodynamics of onvansertib in combination with FOLFIRI + bevacizumab or FOLFOX + bevacizumab in patients with KRAS or NRAS-mutated metastatic colorectal cancer (CRC) in the first-line setting.

开始日期2024-02-27

申办/合作机构

Cardiff Oncology, Inc.

[+1]

100 项与 Onvansertib 相关的临床结果

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100 项与 Onvansertib 相关的转化医学

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100 项与 Onvansertib 相关的专利（医药）

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项与 Onvansertib 相关的文献（医药）

2025-12-31·JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY

High-throughput virtual screening, identification and in vitro biological evaluation of novel inhibitors of PLK1 and NRP1

Article

作者: Zhang, Qi ; Niu, Miao-Miao ; Shen, Xiaozhou ; Han, Gaohua ; Bu, Qian ; Chang, Yuting ; Geng, Yifei ; Guan, Lixia ; Xia, Yang

Overexpression of PLK1 and NRP1 correlate with enhanced proliferative activity in lung cancer cells, thus the development of dual-target PLK1/NRP1 inhibitors holds great therapeutic promise. In this study, five compounds (PLN 1-5) targeting both PLK1 and NRP1 were identified using a multi-step virtual screening approach. PLN-5 showed nanomolar inhibitory potency against PLK1 (IC₅₀ = 2.07 ± 0.13 nM) and NRP1 (IC₅₀ = 5.15 ± 0.24 nM), exceeding the positive controls onvansertib and EG00229 by approximately 9-fold and 124-fold, respectively. Molecular dynamics (MD) simulations revealed that PLN-5 maintained a stable binding to the active sites of PLK1 and NRP1. Importantly, MTT assays showed that PLN-5 had significant antiproliferative activity (IC₅₀ = 0.27 ± 0.02 μM) against human lung cancer cells, with no significant inhibitory effect on normal lung cells. In conclusion, these results demonstrate the therapeutic potential of PLN-5 as a dual-targeting antitumor agent that warrants further development.

2025-11-11·ONCOGENE

PLK1-mediated PDHA1 phosphorylation drives metabolic reprogramming in lung cancer

Article

作者: Peng, Jia ; Liu, Xiaoqi ; Zhang, Qiongsi ; Liu, Jinghui ; Zhang, Yanquan ; Kong, Yifan ; Wang, Ruixin ; Li, Zhiguo ; Katz, Wendy ; Rao, Xiongjian ; Allison, Derek B

Although the involvement of polo-like kinase 1 (PLK1) in metabolic reprogramming from oxidative phosphorylation (OXPHOS) to glycolysis has been previously described, the underlying molecular mechanism remains unclear. Pyruvate dehydrogenase (PDH) catalyzes the conversion of pyruvate into acetyl-CoA, the starting material for the tricarboxylic acid (TCA) cycle. In a companion study by Zhang et al., we demonstrated that PLK1 phosphorylation of PDHA1 at threonine 57 (PDHA1-T57) drives its protein degradation via mitophagy activation. Using a stable-isotope resolved metabolomics (SIRM) approach, we now show that PLK1 phosphorylation of PDHA1-T57 results in metabolic reprogramming from OXPHOS to glycolysis. Notably, cells mimicking PDHA1-T57 phosphorylation rely more on the aspartate-malate shuttle than on glucose-derived pyruvate to sustain the TCA cycle. This metabolic shift was also observed in mouse embryonic fibroblasts (MEFs) and transgenic mice conditionally expressing the PDHA1-T57D variant, highlighting the role of PLK1 in metabolic reprogramming in vivo. It is well-established that pyruvate dehydrogenase kinase (PDK)-mediated phosphorylation of PDH leads to its inactivation and that dichloroacetic acid (DCA), a PDK inhibitor, has been investigated in preclinical and early clinical studies as a potential therapeutic agent for lung cancer. We demonstrated that DCA combined with Onvansertib, a PLK1 inhibitor, synergistically inhibits lung tumor growth by enhancing mitochondrial ROS, inhibiting glycolysis, and inducing apoptosis. This study aims to elucidate how PLK1-associated activity drives the metabolic reprogramming from OXPHOS to glycolysis during cellular transformation, thereby contributing to lung carcinogenesis. Our results provide support for a clinical trial to evaluate the efficacy of Onvansertib plus DCA in treating lung cancer.

2025-09-01·BIOMEDICINE & PHARMACOTHERAPY

Single-cell transcriptomic and pharmacological studies of onvansertib for small cell lung cancer treatment

Article

作者: Choi, Insung ; Jeon, Hyeon Do ; Lee, Gi Bbeum ; Ahn, Seong Hye ; Yon, Dong Keon ; Baek, Inwha ; Lee, Hwajin ; Jung, Junyang ; Park, Jaejung ; Kim, Ja-Eun ; Song, Woojeung ; Lee, Ji Hyun

Polo-like kinase 1 (PLK1), a serine/threonine protein kinase, plays a crucial role in essential biological processes such as cell division, DNA damage response, and cell death. Since its dysregulation is highly associated with tumor development and progression, PLK1 inhibitors, including onvansertib, have been developed as promising anti-cancer therapeutics. Onvansertib is currently under Phase II investigation to evaluate its safety and efficacy in patients with relapsed small cell lung cancer (SCLC). In this study, the efficacy, tolerability, and toxicity of onvansertib were comprehensively profiled using a large panel of 144 cancer cell lines and mouse models. We identified that SCLC cell lines are highly responsive to onvansertib. SCLC xenograft assays showed that daily oral administration of onvansertib at 60 mg/kg was more effective in tumor regression without inducing significant changes in body weight compared to a treatment cycle of 3 days of administration followed by 4 days of rest over a 3-week experimental period. However, in vivo toxicity studies revealed onvansertib-related mortality, clinical signs, and hematological adverse effects at the 60 mg/kg dose. Our findings collectively provide experimental evidence to support combination therapies or toxicity-salvaging low-dose regimens, as reflected in current clinical trials of onvansertib. Additionally, we conducted single-cell RNA-sequencing to elucidate the pharmacological mechanisms of onvansertib in SCLC with unprecedented resolution. Onvansertib impairs a normal cell cycle transition by downregulating the cell division process, leading to G2/M phase arrest. Altogether, this work demonstrates the therapeutic mechanisms and in vitro and in vivo pharmacological profiles of onvansertib in SCLC.

项与 Onvansertib 相关的新闻（医药）

2025-09-25

·学术经纬

50岁以下患者激增，死亡率全球第二的癌种！多款新药正为患者带来新希望

编者按：结直肠癌是全球最常见的恶性肿瘤之一，其发病率和死亡率居高不下。近年来，该领域治疗手段不断进步，患者的选择日益丰富，疾病治疗状况得到了极大改善。但当前临床仍面临诸多挑战。令人期待的是，目前全球有数百项结直肠癌新药研发管线处于临床研究阶段，为结直肠癌患者带来新的希望。作为医药创新的赋能者，药明康德长期以来通过独特的CRDMO模式，持续助力全球合作伙伴加速包括结直肠癌在内的各类癌症创新药物研发，推动更多突破性疗法早日落地，为战胜结直肠癌贡献力量。结直肠癌是全球范围内严重威胁人类健康的主要恶性肿瘤之一。根据CA：A Cancer Journal for Clinicians发布的2022年全球癌症统计报告，结直肠癌的发病率位居全球癌症谱第三位，其死亡率位列癌症相关死亡原因第二位。更值得警惕的是，近年来结直肠癌发病呈现显著的“年轻化”趋势——50岁以下患者占比持续攀升，成为公共卫生领域的重要挑战之一。目前，结直肠癌领域已建立起多手段协同的综合治疗体系。除手术和传统放化疗之外，近年来靶向治疗和免疫治疗等领域取得的突破，为携带特定分子标志物的患者带来了更长的生存获益，也推动结直肠癌治疗逐步进入“精准化”时代。尽管治疗手段日益丰富，结直肠癌的整体预后仍不理想，尤其是转移性结直肠癌，其治疗形势依然严峻，5年生存率在15%以下。更严峻的是，对于经手术、放化疗、靶向及免疫等多线方案治疗后仍出现疾病进展的“难治性”结直肠癌患者，其后续生存期往往进一步缩短。这类患者的未竟医疗需求尤为迫切。为响应这一需求，全球目前针对结直肠癌的临床在研管线项目有数百个，覆盖各类创新靶点和创新分子类型。长期以来，药明康德始终支持包括结直肠癌在内的各类癌症创新疗法的研发，依托“一体化、端到端”的CRDMO模式，助力合作伙伴将科学突破高效转化为创新药物。在全球监管机构批准的数十款结直肠癌治疗药物中，就有多款得到了药明康德的支持。图片来源：123RF 2025年以来，结直肠癌新药研发领域迎来多项新进展。小分子靶向疗法迎来多项突破 1月，安进（Amgen）开发的KRAS G12C抑制剂Lumakras（sotorasib）联合EGFR抑制剂Vectibix（panitumumab）获美国FDA批准，用于治疗携带KRAS G12C突变且既往接受过特定化疗的转移性结直肠癌（mCRC）患者。这一联合方案的上市，为此类患者提供了新的治疗选择。 5月，辉瑞（Pfizer）公布了其BRAF V600E抑制剂Braftovi（恩考芬尼，encorafenib）联合西妥昔单抗与化疗方案mFOLFOX6的3期临床数据。结果显示，该联合方案较现有标准治疗可将BRAF V600E突变mCRC患者的死亡风险降低51%。随后在7月，中国国家药品监督管理局（NMPA）批准恩考芬尼联合西妥昔单抗用于既往接受过系统治疗的BRAF V600E突变mCRC患者。 8月，Cardiff Oncology公布其PLK1抑制剂onvansertib联合标准治疗（SOC）一线治疗RAS突变mCRC的2期临床数据。结果显示，30mg剂量组的客观缓解率（ORR）达到49%，显著高于对照组的30%；同时，该联合方案还显著改善了患者的早期无进展生存期（PFS），且整体耐受性良好。PLK1是Polo样激酶家族成员之一，在多种实体瘤和血液癌症中高度表达，且被认为是维持细胞正常分裂的基石之一。研究显示，RAS的激活会引发PLK1的激活，导致细胞分裂和肿瘤增殖，因此，通过抑制PLK1的活性，onvansertib有望抑制肿瘤生长。同月，Larkspur Biosciences首次公开其口服小分子降解剂LRK-4189的分子结构。该药物通过靶向脂质激酶PIP4K2C，在结直肠癌临床前模型中表现出显著的抗肿瘤活性，无论单药或联合化疗均有效。目前，LRK-4189的新药临床试验申请（IND）所需的前期研究已完成，预计将在2025年第四季度启动1期临床试验。PIP4K2C已被证实与结直肠癌等多种肿瘤的不良预后密切相关，肿瘤细胞通过利用PIP4K2C提升生存能力，避免免疫监视并耐受压力。免疫治疗持续拓宽患者人群在结直肠癌患者中，微卫星高度不稳定（MSI-H）与错配修复缺陷（dMMR）是两类常见的遗传异常。这类变异会影响细胞内的DNA修复机制，导致肿瘤细胞突变积累和肿瘤突变负荷增高，从而增强免疫原性。因此，MSI-H/dMMR型肿瘤通常对免疫治疗更为敏感。 2025年以来，免疫治疗在结直肠癌领域的应用持续拓展，从传统的MSI-H/dMMR优势亚型，逐步延伸至微卫星稳定（MSS）及耐药等更难治的患者群体。在非MSI-H型mCRC方面，Exelix公司于6月公布了其多靶点酪氨酸激酶抑制剂zanzalintinib联合PD-L1抑制剂Tecentriq（阿替利珠单抗，atezolizumab）用于经治非MSI-H型mCRC的3期研究数据。结果显示，该联合疗法显著延长了患者的总生存期，为此类mCRC患者提供了后线治疗的潜在策略。对于MSI-H/dMMR型mCRC患者，免疫检查点抑制剂的组合方案展现出显著疗效。2月，百时美施贵宝（Bristol Myers Squibb）公布了PD-1抑制剂Opdivo（纳武利尤单抗，nivolumab）联合CTLA-4抑制剂Yervoy（伊匹木单抗，ipilimumab）治疗MSI-H/dMMR型mCRC的3期长期随访数据。结果显示，在所有治疗线中，该联合方案较Opdivo单药可降低38%的疾病进展或死亡风险。基于该结果，美国FDA于4月正式批准其用于不可切除或转移性MSI-H/dMMR结直肠癌的一线治疗。针对耐药患者的创新疗法也取得进展。Marengo Therapeutics在4月公布了其T细胞激活剂invikafusp alfa的1/2期临床试验更新结果：该药物在肿瘤突变负荷高（TMB-H）、PD-1/PD-L1抑制剂耐药的难治性癌症（含结直肠癌）中展现出显著疗效，疾病控制率达67%，并已获得FDA授予快速通道资格。此外，对于免疫治疗不敏感的MSS型mCRC，癌症疫苗疗法带来了新希望。6月，Enterome公司公布了其癌症疫苗EO4010联合纳武利尤单抗±贝伐珠单抗（bevacizumab）治疗MSS/错配修复正常型mCRC的1/2期试验积极结果：联合治疗组的12个月生存率达40%，中位生存期为11.3个月，为这一传统上被视为免疫治疗“冷肿瘤”的CRC亚型提供了通过疫苗激活抗肿瘤免疫应答的新治疗策略。自2025年以来，还有其他许多结直肠癌新药管线取得临床进展，此处不再一一列举，我们期待未来能见证更多研发成果涌现。一体化CRDMO平台助力结直肠癌治疗持续创新多年来，全球结直肠癌治疗领域取得了长足进步，数十种新药相继获批上市。尤其对于难治性转移性结直肠癌这一治疗选择长期受限的群体，持续涌现的创新方案为患者带来了生命延续的曙光。尽管如此，转移性结直肠癌的治疗仍面临着肿瘤异质性高、耐药问题突出等重大挑战。目前，全球医药界正通力合作、携手攻坚，不断推动该领域向前发展。权威期刊Nature Reviews Clinical Oncology今年发表的一篇论文指出，随着更多临床试验数据的持续积累，靶向疗法已成为携带明确癌症驱动基因突变患者的重要选择。为进一步提高疗效，未来需优化现有药物及联合治疗策略，并深入探索肿瘤的耐药机制，以寻找逆转耐药的有效途径。与此同时，免疫治疗也亟待突破，有必要加强转化研究，以发现可精准预测免疫检查点抑制剂疗效的生物标志物，并开发新策略，以惠及肿瘤免疫原性较低的结直肠癌患者群体。在推动结直肠癌治疗方案持续创新的过程中，药明康德始终致力于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。在医药创新生态圈的合力下，我们坚信，更多突破性疗法将不断涌现，为结直肠癌患者带来更多新的曙光。参考资料： [1] Colorectal Cancer. Retrieved September 8, 2025, from https://www.aacr.org/patients-caregivers/cancer/colorectal-cancer/ [2] COLORECTUM. Retrieved September 8, 2025, from https://gco.iarc.who.int/media/globocan/factsheets/cancers/41-colorectum-fact-sheet.pdf [3] What Is Colorectal Cancer? Retrieved September 8, 2025, from https://www.cancer.org/cancer/types/colon-rectal-cancer/about/what-is-colorectal-cancer.html [4] Bray, Freddie et al. “Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.” CA: a cancer journal for clinicians vol. 74,3 (2024): 229-263. doi:10.3322/caac.21834 [5] Ciracì, Paolo et al. “Late-line options for patients with metastatic colorectal cancer: a review and evidence-based algorithm.” Nature reviews. Clinical oncology vol. 22,1 (2025): 28-45. doi:10.1038/s41571-024-00965-0 [6] Pericay, Carles et al. “Real-World Outcomes in Patients with Metastatic Colorectal Cancer in Spain: The RWD-ACROSS Study.” Cancers vol. 15,18 4603. 17 Sep. 2023, doi:10.3390/cancers15184603 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「医药观澜」微信公众号回复“转载”，获取转载须知。

免疫疗法突破性疗法临床3期

2025-08-01

·药明康德

强效降脂近90%！赛诺菲助力潜在“first-in-class”疗法开发；诺和诺德单抗再获FDA批准……

强效降脂近90%！赛诺菲近4亿美元助力潜在“first-in-class”疗法开发Arrowhead Pharmaceuticals今日宣布，其控股子公司维亚臻（Visirna Therapeutics）与赛诺菲（Sanofi）签署协议。根据协议条款，赛诺菲将获得在大中华区开发和商业化在研疗法plozasiran（VSA001）的独家权利。Plozasiran是一款潜在“first-in-class”的siRNA疗法，旨在抑制载脂蛋白C-III（APOC3）的产生，用于治疗家族性乳糜微粒血症综合征（FCS）及重度高甘油三酯血症（SHTG）。根据协议，赛诺菲将向维亚臻支付1.3亿美元的预付款，并在未来根据监管里程碑支付最高2.65亿美元。维亚臻此前已完成在中国FCS患者中的plozasiran临床3期试验，试验成功达到主要疗效终点及所有关键次要终点。之前公布的试验结果显示，plozasiran在第10个月使患者的中位甘油三酯水平降低高达89%，中位APOC3水平降低高达93%，与安慰剂组相比具有统计学差异。维亚臻已于2025年1月向中国国家药品监督管理局（NMPA）递交新药上市申请，并获得正式受理。此次合作将进一步推动plozasiran在大中华区的临床应用进程，有望为高甘油三酯血症患者带来新的治疗选择。诺和诺德单抗再获FDA批准诺和诺德（Novo Nordisk）日前宣布，美国FDA已批准Alhemo（concizumab）注射液用于预防或减少血友病A（HA）与血友病B（HB）成人及儿科患者的出血发作频率，这些患者年龄12岁及以上且体内无抑制物。新闻稿指出，当前多数无抑制物血友病患者的治疗多依赖静脉输注，而Alhemo作为一种每日一次的皮下注射药物，为该人群提供了更便捷的预防治疗选择。Alhemo是一种组织因子途径抑制剂（TFPI）拮抗剂，此次批准是在2024年12月获批适应症（用于体内含有抑制物的HA/HB患者）基础上的扩展。此次批准主要基于3期临床试验explorer8的结果，研究证实Alhemo在12岁及以上无抑制物的HA/HB患者中具有良好的安全性与疗效。试验显示，在无抑制物的HB患者中，年化出血率（ABR）降低79%；在HA患者中，ABR降低幅度更高，达到86%。近半晚期RAS突变癌症患者获得缓解，小分子抑制剂积极结果公布Cardiff Oncology近日公布其正在进行的CRDF-004试验的积极结果。该研究是一项随机的2期临床试验，评估候选小分子onvansertib联合标准治疗（SoC）在一线RAS突变型转移性结直肠癌（mCRC）患者中的疗效与安全性。数据显示，在意向治疗人群（N=110）中，接受30 mg剂量onvansertib治疗的患者组确认客观缓解率（ORR）达49%，显著优于对照组的30%。此外，早期无进展生存期（PFS）数据亦显示出30 mg onvansertib组较对照组具有更好的临床获益。研究进一步表明，onvansertib在多个疗效指标上展现出剂量依赖性的积极应答，包括早期肿瘤缩小率及缓解深度，且整体耐受性良好。这一结果支持onvansertib作为一线治疗RAS突变型mCRC的潜力。Onvansertib是一种潜在“first-in-class”的第三代口服PLK1抑制剂。PLK1是Polo样激酶家族成员之一，在乳腺癌、前列腺癌、卵巢癌、肺癌和直肠癌等多种实体瘤和血液癌症中高度表达。PLK1被认为是维持细胞正常分裂的基石之一。研究显示，RAS的激活会引发PLK1的激活，导致细胞分裂和肿瘤增殖，因此，通过抑制PLK1的活性，onvansertib有望抑制肿瘤生长。参考资料：[1] Cardiff Oncology Announces Positive Data from Ongoing Randomized Phase 2 First-line RAS-mutated mCRC Clinical Trial (CRDF-004). Retrieved August 1, 2025 from https://investors.cardiffoncology.com/news-releases/news-release-details/cardiff-oncology-announces-positive-data-ongoing-randomized[2] FDA approves Alhemo® as once-daily prophylactic treatment to prevent or reduce the frequency of bleeding episodes for adults and children 12 years of age and older with hemophilia A or B (HA/HB) without inhibitors. Retrieved August 1, 2025 from https://www.prnewswire.com/news-releases/fda-approves-alhemo-as-once-daily-prophylactic-treatment-to-prevent-or-reduce-the-frequency-of-bleeding-episodes-for-adults-and-children-12-years-of-age-and-older-with-hemophilia-a-or-b-hahb-without-inhibitors-302519177.html[3] Arrowhead Subsidiary Visirna Sells Rights to Hypertriglyceridemia Candidate Plozasiran in Greater China to Sanofi. Retrieved August 1, 2025 from https://www.businesswire.com/news/home/20250801023769/en/Arrowhead-Subsidiary-Visirna-Sells-Rights-to-Hypertriglyceridemia-Candidate-Plozasiran-in-Greater-China-to-Sanofi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期引进/卖出临床结果上市批准siRNA

2025-07-30

·FierceBiotech

Investors whale on Cardiff, sinking stock after seeing updated colorectal cancer data

Cardiff Oncology is aiming to provide an update on its first-line metastatic colorectal cancer program in the first quarter of next year.\n Cardiff Oncology has reported updated results from its phase 2 colorectal cancer trial, laying out data it believes can support talks with the FDA about a registrational program. Investors, though, responded by sending the biotech’s share price down 27% to $2.43 in premarket trading. The phase 2 study is testing Cardiff’s PLK1 inhibitor onvansertib in combination with standard of care in patients with first-line RAS-mutated metastatic colorectal cancer (mCRC). In December, the biotech reported a 64% objective response rate (ORR) on the high dose, compared to a 33% ORR in the control cohort. The gap between the treatment and control arms narrowed in the latest, larger cut of the data.Including unconfirmed responses, the ORR was 59% on the high dose, versus a 43% response rate in the control arm. Removing the unconfirmed responses resulted in ORRs of 49% and 30%, respectively, for the high-dose and control arms. The difference fell short of the 20% targeted by Cardiff, William Blair analysts said in a note to investors. The analysts said the slight miss does not alter onvansertib’s profile.Talking on a conference call with analysts, Cardiff CEO Mark Erlander said the data support \"the next step in our path towards a seamless registrational trial for both accelerated and full approval.” Erlander’s position is built on the belief that the high dose is “clearly outperforming” the control group and that the data compare \"favorably against previous practice-changing trials.” Asked by an analyst whether Cardiff would wait for the data to mature before talking to the FDA, Erlander said, “I think we have to make that call in the next month or two.” The company is “right in the middle of a lot of the PK exposure response data,” the CEO said, but, as it stands, management believes it has the evidence to move forward and to speak with the FDA later in the year.The progression-free survival (PFS) data that could provide a clearer picture of the impact of onvansertib are immature. Median PFS in the first-line setting is nine to 12 months, Erlander said. Cardiff has a median of six months of follow-up. The data that are available show a separation of the PFS curves, with the high dose performing best and the control performing worst, and Erlander believes the signs are encouraging. “Early tumor shrinkage, early responses and depth of response are strongly correlated with improvements in progression-free survival,” the CEO told analysts. “We’re expecting those separations to continue and hopefully become even more clear with more patient follow-up.”Cardiff is aiming to provide an update on the first-line mCRC program in the first quarter of next year.

临床结果临床2期

100 项与 Onvansertib 相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11458	-	-	DB15110

研发状态

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
转移性结直肠癌	临床2期	美国	Cardiff Oncology, Inc.	2023-03-17
HER2 阴性乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
HR阳性乳腺腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
激素受体/生长因子受体阴性乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
炎症性乳腺肿瘤	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
浸润性乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
局部晚期乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
转移性乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
不能切除的乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-30
三阴性乳腺癌	临床2期	美国	Cardiff Oncology, Inc.	2022-09-12

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临床结果

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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


NCT06106308 (CRDF-004, Company_Website) 人工标引	临床2期	RAS 突变结直肠癌一线 NRAS Mutation \| KRAS Mutation	110	Onvansertib 20 mg + SoC	製觸衊艱夢蓋獵糧襯鹹(衊範憲窪襯膚襯獵鹽鏇) = 鬱鏇鑰獵鏇繭艱鹽繭遞鏇遞齋衊鹽鹹膚夢網鹽 (壓獵壓衊糧醖糧壓鏇窪 ) 更多	积极	2025-07-29
				Onvansertib 30 mg + SoC	製觸衊艱夢蓋獵糧襯鹹(衊範憲窪襯膚襯獵鹽鏇) = 鹽餘鹹憲網鑰網廠築鏇鏇遞齋衊鹽鹹膚夢網鹽 (壓獵壓衊糧醖糧壓鏇窪 ) 更多
NCT05383196 (ASCO2025) 人工标引	临床1期	转移性三阴性乳腺癌	17	Onvansertib	壓獵襯獵築鹽顧簾觸壓(衊簾願鹽鹹醖夢築鬱鹽) = DLTs were observed in 0/3 pts at DL0, 1/4 (25%) at DL1, and 3/10 (30%) at DL2. 餘簾蓋淵築醖範襯製願 (夢選觸顧糧餘積網製鏇 ) 更多	积极	2025-05-30
				Onvansertib DL0 9 mg/m²Onvansertib DL0 9 mg/m²
NCT06106308 (CRDF-004, GlobeNewswire) 人工标引	临床2期	RAS 突变结直肠癌一线 KRAS Mutation \| NRAS Mutation	30	Onvansertib 20mgOnvansertib 20mg + SoC	廠觸齋衊願鹹鑰蓋積襯(襯鏇窪夢襯蓋壓範遞遞) = 壓鑰淵淵窪構獵醖獵遞廠願遞淵膚願鏇衊壓鏇 (願衊窪膚築網餘襯淵製 )	积极	2024-12-10
				Onvansertib 30mgOnvansertib 30mg + SoC	廠觸齋衊願鹹鑰蓋積襯(襯鏇窪夢襯蓋壓範遞遞) = 鏇構壓壓壓鬱構築積鹽廠願遞淵膚願鏇衊壓鏇 (願衊窪膚築網餘襯淵製 )
NCT03414034 (CTgov)	临床2期	转移性去势抵抗性前列腺癌	72	prednisone+Abiraterone+Onvansertib (Arm A: Onvansertib + Abiraterone and Prednisone)	蓋鏇鹹網製齋選顧蓋窪 = 鹽壓膚構襯糧廠鹹積構製鬱窪醖觸醖網鏇鏇築 (簾鹹餘鹹淵繭選構顧構, 鹽衊遞襯網簾醖夢觸齋 ~ 獵蓋憲觸衊衊艱鏇壓襯) 更多	-	2024-11-07
				prednisone+Abiraterone+Onvansertib (Arm B: Onvansertib + Abiraterone and Prednisone)	蓋鏇鹹網製齋選顧蓋窪 = 淵蓋構衊築餘顧築憲憲製鬱窪醖觸醖網鏇鏇築 (簾鹹餘鹹淵繭選構顧構, 壓蓋築簾夢選鏇簾艱繭 ~ 願齋鑰壓鏇簾憲憲製醖) 更多
NCT03829410 (CRDF-004, GlobeNewswire) 人工标引	临床2期	KRAS 突变结直肠癌二线 KRAS Mutation	-	Onvansertib with FOLFIRI and bevacizumab (bev-naïve patients)	築簾選範構繭糧壓壓壓(壓築願蓋糧膚憲鹹窪構) = 齋選鏇糧壓鬱製積鹽襯遞窪鬱醖願製窪廠鏇獵 (製憲構襯餘範鏇糧夢餘 ) 更多	积极	2024-10-30
				onvansertib with FOLFIRI and bevacizumab (bev-exposed patients)	築簾選範構繭糧壓壓壓(壓築願蓋糧膚憲鹹窪構) = 獵鹽鏇壓願衊鏇廠憲衊遞窪鬱醖願製窪廠鏇獵 (製憲構襯餘範鏇糧夢餘 ) 更多
NCT06106308 (Pubmed \| J Clin Oncol)	临床2期	KRAS 突变结直肠癌二线 KRAS Mutant	53	Onvansertib + FOLFIRI + Bevacizumab	觸築齋繭醖廠獵製壓淵(醖膚襯簾膚範夢廠鹹壓) = 選醖衊夢鬱遞積夢繭夢遞積廠齋齋網構壓範餘 (鹹壓襯憲築醖網鹹積齋, 15.3 ~ 40.3) 更多	积极	2024-10-30
				Onvansertib + FOLFIRI + Bevacizumab (revealed bevacizumab)	觸築齋繭醖廠獵製壓淵(醖膚襯簾膚範夢廠鹹壓) = 夢淵構築願糧夢壓鏇蓋遞積廠齋齋網構壓範餘 (鹹壓襯憲築醖網鹹積齋 ) 更多
Phase Ib Clinical Study (Pubmed \| Clin Cancer Res)	临床1期	二线 KRAS-mutant	18	Onvansertib 12 mg/m2	窪衊顧繭鏇餘繭廠範觸(構醖鏇窪遞簾夢襯繭艱) = Grade 3 and 4 adverse events (AE) represented 15% of all treatment-related AEs, with neutropenia being the most common 衊膚鹹遞憲鹽選餘淵襯 (鏇醖遞艱範壓淵獵選網 ) 更多	积极	2024-05-15
				Onvansertib 15 mg/m2
NCT03829410 (AACR2024) 人工标引	临床1/2期	KRAS 突变结直肠癌二线 KRAS-mutant	66	Onvansertibbevacizumab	選衊蓋網製蓋觸鬱範範(鹹繭醖蓋醖選積網壓齋) = 鹽製鹽觸艱製窪鹽鬱壓鏇願鏇膚範壓鑰遞積觸 (艱鏇繭廠衊鬱鑰壓膚鏇 ) 更多	积极	2024-03-22
NCT05593328 (ONSEMBLE, GlobeNewswire) 人工标引	临床2期	转移性结直肠癌二线 KRAS Mutation \| NRAS Mutation	23	Onvansertib+SoC	膚鹽顧襯積窪糧壓顧鏇(衊齋衊鬱艱鬱艱鏇蓋鹽) = 窪衊顧襯範遞鑰衊餘顧襯鏇衊觸鹽遞獵廠築齋 (鬱夢鹽構齋網構願選廠 ) 更多	积极	2024-02-29
				Onvansertib+SoC (Bev Naïve patients)	膚鹽顧襯積窪糧壓顧鏇(衊齋衊鬱艱鬱艱鏇蓋鹽) = 夢鏇獵鏇壓遞鹽夢鑰衊襯鏇衊觸鹽遞獵廠築齋 (鬱夢鹽構齋網構願選廠 )
Literature 人工标引	临床1期	KRAS 突变结直肠癌二线 KRAS Mutation	18	Onvansertib+FOLFIRI+Bevacizumab	鑰憲獵遞網襯鏇膚膚鏇(簾選鹹淵獵鑰艱觸積糧) = 鬱構齋遞膚窪夢選襯齋簾獵觸襯築夢壓鬱壓壓 (繭糧鹹顧範衊壓窪膚壓 ) 更多	积极	2024-01-17