A Phase 1, Open-Label Study to Characterize the Metabolism, Excretion, and Mass Balance of a Single Intravenous Dose of 100 mg Containing 75 µCi of [14C]-Quemliclustat in Healthy Adult Male Participants

The purpose of the study is to investigate the routes of elimination and overall mass balance of 100 mg quemliclustat containing 75 μCi [14C] following a single IV infusion of [14C]-quemliclustat in healthy adult male participants, and to quantify total radioactivity (TRA) in plasma, whole blood, urine, and feces.

开始日期2026-02-03

申办/合作机构

Arcus Biosciences, Inc.

NCT06608927

/ Active, not recruiting临床3期

A Randomized, Placebo-Controlled, Double-Blind, Multicenter, Phase 3 Trial of Quemliclustat and Chemotherapy Versus Placebo and Chemotherapy in Patients With Treatment-Naive Metastatic Pancreatic Ductal Adenocarcinoma

The purpose of this study is to compare overall survival of quemliclustat, nab-paclitaxel and gemcitabine versus placebo, nab-paclitaxel and gemcitabine in all randomized patients.

开始日期2024-12-13

申办/合作机构

Arcus Biosciences, Inc.

[+1]

NCT06048484

/ Recruiting临床2期IIT

A Phase 2, Open-Label, Multicenter, Randomized Study Evaluating Neoadjuvant Therapy Targeting the Adenosine Immunosuppressive Pathway in Combination With Immune Checkpoint Blockade and Radiation Therapy in Patients With Advanced PANCreatic Ductal Adenocarcinoma Who Are Candidates for Surgical Resection

The purpose of this study is to combine standard radiation therapy with drugs that encourages the body's immune system against cancer cells and simultaneously adding drugs which also target the pathway that the tumor uses to evade the immune system (CD73 and A2a/b). The study hopes that these drugs will work in concert with radiation therapy to kill cancer cells.
The specific goal of this study is to ensure that treatment with zimberelimab and stereotactic body radiation therapy (SBRT) alone or in combination with quemliclustat (a drug which blocks CD73), with or without etrumadenant (a drug which blocks the A2a/b) given before surgery is safe and if it can further increase the immune response against the tumor.

开始日期2024-05-10

申办/合作机构

Columbia University

[+1]

100 项与 Quemliclustat 相关的临床结果

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100 项与 Quemliclustat 相关的转化医学

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100 项与 Quemliclustat 相关的专利（医药）

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项与 Quemliclustat 相关的文献（医药）

2026-01-09·ACS Pharmacology & Translational Science

Potent Competitive Inhibitors of Ecto-5′-nucleotidase (CD73) based on 6-(Het)aryl-7-deazapurine Ribonucleoside 5′- O -Bisphosphonates

Article

作者: Konvalinka, Jan ; Poštová Slavětínská, Lenka ; Lepšík, Martin ; Šácha, Pavel ; Hocek, Michal ; Šinkevičiu̅tė, Ugnė ; Blažková, Kristýna ; Řezáč, Jan ; Staník, Radek ; Šímová, Magdalena ; Tichý, Michal ; Ormsby, Tereza

CD73 generates immunosuppressive adenosine in the tumor microenvironment and is a promising target for cancer immunotherapy. We have designed and systematically studied diverse 2-substituted 7-deazapurine ribonucleoside 5'-O-bisphosphonates bearing a variety of (het)-aryl groups at position 6 and discovered their highly potent and selective CD73 inhibition activity. The most active compounds (with single-digit picomolar K _i) contained bicyclic (het)-aryl groups at position 6 in combination with chlorine at position 2. Further optimization of pharmacokinetic properties identified inhibitors with low clearance, long half-life, high solubility, and excellent selectivity over CD39 and NTPDase3. They effectively suppressed adenosine formation in MDA-MB-231 cells, rescued CD8⁺ T cell activation, and were nontoxic to human fibroblasts. Overall, their profile compares favorably with AB680, a CD73 inhibitor currently in phase I/II clinical trials.

2025-11-01·ACTA PHARMACOLOGICA SINICA

CD73 inhibitor AB680 suppresses glioblastoma in mice by inhibiting purine metabolism and promoting P2RY12+ microglia transformation

Article

作者: Ding, Ze-Hua ; Wan, Yu-Wei ; Gao, Pan-Pan ; An, Qi ; Yin, En-Zhi ; Jiang, Hai-Feng ; Xu, Xiao-Hong ; Liang, Xin-Xin ; Li, Ming-Feng ; Du, Yu-Wen ; Shu, Ya ; Liu, Feng ; Chen, Xiao-Qian ; Miao, Cheng ; Wu, Jia-Xing ; He, Xi-Miao ; Wang, Si-Dao

CD73 (ecto-5'-nucleotidase) is a metabolic immune checkpoint that dephosphorylates AMP to produce adenosine. Adenosine plays a pivotal role in immunosuppressive tumor microenvironment (TME) through adenosine receptors expressed on various immune cells. AB680, a specific CD73 inhibitor, is currently undergoing clinical trials for highly refractory cancers. In this study, we investigated the antitumor effects and mechanisms of AB680 in glioblastoma (GBM). By analyzing the expression pattern of CD73 across all cell types in orthotopic naïve G422^TN-GBM tumors (d 7), we found that CD73 and its associated adenosine metabolic signaling were significantly elevated in G422^TN-GBM cells compared to all other cell types. High CD73 expression was also observed in human GBM samples and was correlated with shorter patient survival. Administration of AB680 significantly prolonged survival in G422^TN-GBM-bearing mice, reduced tumor size, cell proliferation, angiogenesis, and enhanced microglia activation and anti-tumor immune responses. Metabolomic analysis revealed that AB680 markedly increased ADP and AMP levels in the TME of orthotopic G422^TN-GBM, thereby stimulating the activation of P2RY12⁺ microglia to exert their M1-like anti-cancer functions, as confirmed by human GBM scRNA-seq and G422^TN-GBM snRNA-seq data. Furthermore, AB680 combined with RT/TMZ exhibited synergistic therapeutic effects by reversing RT/TMZ-induced increases in adenosine levels and promoting the transformation of P2RY12⁺ microglia. Overall, this study demonstrates that targeting CD73 with AB680 alters purine metabolism in the GBM microenvironment, promotes the transformation of P2RY12⁺ microglia, and triggers robust anti-tumor immune responses. These results support the rationale for AB680-based therapeutic clinical trials for GBM.

2025-04-10·JOURNAL OF MEDICINAL CHEMISTRY

Development of CD73 Inhibitors in Tumor Immunotherapy and Opportunities in Imaging and Combination Therapy

Review

作者: Patel, Jimmy S. ; Liang, Steven H. ; Bi, Chunyang

CD73 is a member of the membrane-bound enucleotidase family, which catalyzes the extracellular hydrolysis of adenosine monophosphate (AMP) to produce anti-inflammatory and immunosuppressive adenosine. As a novel checkpoint protein, CD73 is overexpressed in the immune system of various tumors, where adenosine is abundantly enriched. A large number of monoclonal antibodies (mAbs), nucleotides, and non-nucleotides as potent CD73 inhibitors are being discovered, providing opportunities for novel tumor immunotherapy. Currently, 18 CD73 inhibitors are in clinical trials, showing promising results in combination therapy for various solid tumors. The development of CD73-specific companion positron emission tomography imaging ligands holds potential for facilitating diagnosis, patient selection, and treatment efficacy evaluation throughout the entire process of CD73-targeted therapeutic development.

项与 Quemliclustat 相关的新闻（医药）

2026-04-01

·医学新视点

《自然-医学》：“癌王”治疗迎曙光，CD73抑制剂联合化疗，有望为胰腺癌患者带来更好生存结局

胰腺癌被称为“癌中之王”，是最致命的恶性疾病之一，预计到2030年将成为癌症的第二大死因。尽管临床已有多种治疗策略，但晚期胰腺癌患者的总生存期仍有待提高。Quemliclustat是一种强效的CD73选择性小分子抑制剂，能够有效阻断腺苷的产生，从而恢复免疫系统的正常功能，目前正在多种肿瘤中开展相关探索研究。近日，ARC-8的1b期研究结果发表于《自然-医学》（Nature Medicine），表明在未经治疗的转移性胰腺癌患者中，使用quemliclustat联合化疗（吉西他滨/白蛋白紫杉醇），经确认客观缓解率（ORR）为38%、经确认的疾病控制率（DCR）为86%、中位缓解持续时间（DOR）为5.5个月、中位总生存期（OS）为19.4个月、中位无进展生存期（PFS）为8.8个月，展现出具有潜力的治疗效果，值得临床关注。截图来源：Nature Medicine ARC-8试验是一项正在进行中的开放标签研究，采用了经典的两阶段设计。研究纳入经细胞学或组织学诊断为转移性胰腺导管癌、既往未接受过相应治疗的患者。第一阶段为剂量递增阶段，共纳入22例患者，探索了不同剂量（25 mg~125 mg）的quemliclustat+化疗（G/nP，吉西他滨/白蛋白结合型紫杉醇）+PD-1抑制剂赛帕利单抗（zimberelimab）的安全性，最终确定了quemliclustat 100 mg为后续研究的推荐剂量。第二阶段为剂量扩展阶段，116例患者被随机分配接受quemliclustat+化疗，或quemliclustat+化疗+zimberelimab。剂量扩展阶段数据截止时（2022年2月28日），中位生存随访时间为21.1个月。双联治疗组的疗效表现较三联治疗组更优，具体而言： ORR：双联治疗组和三联治疗组经确认/未经确认的ORR分别为38%/41%和25%/34%； DCR：经确认/未经确认的DCR相同，双联治疗组和三联治疗组分别为86%和72%；中位DOR：双联治疗组为5.5个月，长于三联治疗组的3.7个月；中位OS：双联治疗组长于三联治疗组（19.4个月 vs. 14.6个月）；中位PFS：双联治疗组仍更长（8.8个月 vs. 4.9个月）。事后分析发现，截至2023年6月19日，中位生存随访时间为21个月。两个研究阶段的所有接受quemliclustat 100 mg治疗的患者（122例），经确认/未经确认的ORR分别为29%/39%，经确认/未经确认的DCR均为78%，DOR为5.4个月，中位OS达到了15.7个月，中位PFS为6.3个月。此外，研究还进行了另一项事后探索性分析，通过统计学方法构建了一个“合成对照组”，该对照组由历史临床试验中仅接受化疗的患者经匹配后构成。与这个合成对照组为9.8个月的中位OS数据相比，接受quemliclustat 100 mg治疗（15.7个月）将患者中位OS显著延长了5.9个月（P=0.003）。安全性方面，未发现quemliclustat或zimberelimab有新的安全性特征。 ARC-8研究结果支持CD73可作为胰腺导管癌的治疗靶点，以及quemliclustat作为转移性胰腺导管癌患者中的治疗策略。文章指出，一项名为PRISM-1的3期临床研究正在进行中，旨在明确quemliclustat+化疗与安慰剂+化疗的疗效和安全性特征。点击文末“阅读原文/Read more”，即可访问期刊官网阅读完整论文。推荐阅读 NEJM：新药在胰腺癌、乳腺癌、结直肠癌等多种实体瘤中展现抗肿瘤活性，这些患者获益更大《自然-医学》：突破胰腺癌治疗瓶颈，细胞疗法展现治疗潜力减少化疗，疗效相当，还更安全！《柳叶刀》子刊：转移性胰腺癌新治疗策略题图来源：123RF 参考资料 [1] Wainberg, Z.A., Manji, G.A., Bahary, N. et al. Quemliclustat and chemotherapy with or without zimberelimab in metastatic pancreatic adenocarcinoma: a randomized phase 1 trial. Nat Med (2026). https://doi.org/10.1038/s41591-026-04283-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「医学新视点」微信公众号留言联系。如有其他合作需求，请联系wuxi_media@wuxiapptec.com 分享，点赞，在看，传递医学新知

2026-03-26

·药时空

胰腺癌治疗全景：前沿靶点、临床格局与千亿市场预测

胰腺癌因其高侵袭性、低生存率、治疗选择有限，成为全球恶性肿瘤中最棘手的癌种之一。本文系统梳理胰腺导管腺癌（PDAC）与胰腺神经内分泌肿瘤（pNETs）的标准治疗、靶向及免疫最新进展、后期临床在研药物，并给出2025—2034年市场规模预测，为临床与产业决策提供参考。一、疾病概况：两类胰腺癌，预后天差地别胰腺癌的癌症相关死亡人数与发病率极不匹配，凸显其恶性程度极高。外分泌肿瘤（90%–95%）以胰腺导管腺癌（PDAC）为主，起源于胰腺导管上皮，5年生存率仅约13%。胰腺神经内分泌肿瘤（pNETs，<5%）起源于激素分泌型胰岛细胞，恶性程度相对较低，5年生存率约50%。二、当前标准治疗1. 胰腺导管腺癌（PDAC）（1）可切除术后：辅助化疗体能状态好（ECOG 0–1）改良FOLFIRINOX（mFOLFIRINOX）：5‑氟尿嘧啶+亚叶酸钙+伊立替康+奥沙利铂，剂量调整后疗效与毒性更平衡。体能状态差/合并症多（ECOG 2）吉西他滨±卡培他滨。（2）不可切除局部晚期/转移：一线化疗标准方案： mFOLFIRINOX 吉西他滨 + 白蛋白结合型紫杉醇 2024年FDA新获批方案：NALIRIFOX 含脂质体伊立替康，相比FOLFIRINOX：更低血液学毒性、更少神经病变腹泻发生率更高（3）二线化疗一线用FOLFIRINOX → 二线以吉西他滨为基础方案一线用吉西他滨 → 二线脂质体伊立替康 + 5‑FU + 亚叶酸钙（4）分子靶向治疗（仅适用于特定亚型） BRCA胚系突变（4%–7%）奥拉帕利（PARP抑制剂）：一线铂类化疗≥16周未进展后的维持治疗。 MSI‑H/dMMR（1%–2%）帕博利珠单抗（PD‑1抑制剂）：后线治疗。 NRG1融合（1%–3%）泽诺妥珠单抗（HER2×HER3双抗）：FDA加速批准，用于既往治疗进展后。2. 胰腺神经内分泌肿瘤（pNETs）（1）早期手术切除为根治手段。（2）晚期/不可切除/转移控制激素症状：生长抑素类似物：奥曲肽、兰瑞肽（一线标准）。全身治疗：依维莫司（mTOR抑制剂）舒尼替尼、卡博替尼（TKI） 177Lu‑Dotatate（肽受体放射性核素治疗PRRT）适用于SSTR阳性（90%–95%）、生长抑素类似物进展后的GEP‑NETs。三、新兴疗法：后期管线重点靶点1. PDAC核心在研药物（1）RAS(ON)抑制剂：daraxonrasib 覆盖90%–95% RAS突变晚期PDAC 多项III期研究进行中，覆盖：既往治疗的转移患者术后辅助治疗一线联合化疗 2025年获： FDA突破性疗法认定（BTD）孤儿药资格（ODD）专员国家优先券（CNPV）（2）其他后期在研靶点 CD73抑制剂：quemliclustat 联合化疗（III期） PRMT5抑制剂：navlimetostat（针对MTAP缺失，约21%患者）多胺类似物：ivospemin GSK‑3β抑制剂：elraglusib（II期达到主要终点） MEK抑制剂：atebimetinib（2026年将启动全球III期）2. pNETs新兴疗法新型放射性药物 177Lu‑edotreotide：FDA审评中，PDUFA 2026-08-28 225Ac‑Dotatate：用于既往PRRT进展后新一代TKI：zanzalintinib表 1 | 胰腺癌在研药物精选靶点类似卡博替尼，但半衰期更短，用于晚期pNETs。四、市场预测：2034年逼近百亿美元据科睿唯安（Clarivate）预测：整体市场 2025年：32亿美元 2034年：97亿美元 PDAC（占绝对主体） 2025年：25亿美元 2034年：88亿美元 2025年主力：白蛋白结合型紫杉醇（12亿美元） 2034年主力： RAS抑制剂（daraxonrasib）：38亿美元 MEK抑制剂（atebimetinib）：15亿美元吉西他滨+白蛋白紫杉醇：近20亿美元 pNETs市场 2034年：接近10亿美元放射性药物 + TKI 合计约4.6亿美元按药物类别划分的主要市场胰腺癌核心疗法销售额预估要点总结 1.PDAC仍是预后最差的常见实体瘤，化疗仍为基石，RAS、MEK、CD73、PRMT5是未来突破方向。 2.分子分型（BRCA、MSI‑H、NRG1）已真正改变胰腺癌治疗模式。 3.pNETs走向长效生长抑素类似物 + 靶向 + PRRT的精准阶梯治疗。 4.2030年后，RAS抑制剂将重塑胰腺癌市场与临床格局。原文DOI：https://doi.org/10.1038/d41573-026-00027-3 识别微信二维码，可添加药时空小编请注明：姓名+研究方向！

临床3期孤儿药突破性疗法临床结果加速审批

2026-03-25

·BioSpace

Arcus Biosciences Announces New Employment Inducement Grants - March 24, 2026

HAYWARD, Calif.--(BUSINESS WIRE)--Arcus Biosciences, Inc. (NYSE:RCUS), a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules and combination therapies for people with cancer and inflammatory and autoimmune disorders, today announced that the Compensation Committee of the Company’s Board of Directors granted two new employees options to purchase a total of 7,050 shares of the Company’s common stock at an exercise price per share of $21.41, which was the closing price on March 23, 2026, and restricted stock units to acquire a total of 3,550 shares of the Company’s common stock. The equity awards were granted pursuant to the Company’s 2020 Inducement Plan, which was approved by the Company’s Board of Directors in January 2020 pursuant to the “inducement exception” under NYSE Listed Company Manual Rule 303A.08. About Arcus Biosciences Arcus Biosciences is a clinical-stage, global biopharmaceutical company focused on developing differentiated molecules for the treatment of cancer and inflammatory and autoimmune diseases. In partnership with industry collaborators, patients and physicians around the world, Arcus is expediting the development of its late-stage portfolio of first- and/or best-in-class medicines against well-characterized biological targets and pathways and studying novel, biology-driven combinations that have the potential to help people with cancer live longer. Founded in 2015, the company has advanced multiple investigational medicines into registrational clinical trials including casdatifan, a HIF-2a inhibitor for clear cell renal cell carcinoma, and quemliclustat, a small-molecule CD73 inhibitor for pancreatic cancer. For more information about Arcus Biosciences’ clinical and preclinical programs, please visit . Inducement PR Source: Arcus Biosciences Contacts Investor & Media Inquiries: Holli Kolkey VP of Corporate Communications (650) 922-1269 hkolkey@arcusbio.com Maryam Bassiri Director, Corporate Affairs (510) 406-8520 mbassiri@arcusbio.com

100 项与 Quemliclustat 相关的药物交易

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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
转移性胰腺导管腺癌	临床3期	美国	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	日本	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	澳大利亚	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	奥地利	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	比利时	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	加拿大	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	捷克	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	法国	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	德国	Arcus Biosciences, Inc.	2024-12-13
转移性胰腺导管腺癌	临床3期	意大利	Arcus Biosciences, Inc.	2024-12-13

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临床结果

适应症

分期

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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


NCT04104672 (ARC-8, ASCO_GI2024) 人工标引	临床1期	转移性胰腺腺癌一线 NT5E	122	quemliclustat+gemcitabine/nab-paclitaxel	顧夢選積獵鹽鬱醖艱膚(繭築網鏇鑰範鏇醖夢憲) = 膚憲蓋製艱衊憲鹽鹹顧艱鏇壓齋構夢壓遞鹽鹹 (選鬱糧衊構醖網憲遞餘, 24 ~ 61) 更多	积极	2024-01-18
NCT04104672 (ARC-8, ASCO_GI2024) 人工标引	临床1期	转移性胰腺腺癌一线 NT5E	122	quemliclustat+gemcitabine/nab-paclitaxel+zimberelimab	顧夢選積獵鹽鬱醖艱膚(繭築網鏇鑰範鏇醖夢憲) = 膚齋膚網廠淵憲襯鏇積艱鏇壓齋構夢壓遞鹽鹹 (選鬱糧衊構醖網憲遞餘, 28 ~ 48) 更多	积极	2024-01-18
NCT04104672 (ASCO_GI 12021 \| ASCO_GI 22021) 人工标引	临床1期	转移性胰腺腺癌一线	13	overall	繭餘醖淵構顧簾簾艱夢(構艱淵願襯艱艱顧廠廠) = 壓顧製憲築構夢願餘構蓋積顧獵簾鏇膚齋遞獵 (簾遞醖鑰襯鹹鏇選齋膚 ) 更多	积极	2021-01-20
NCT04104672 (ASCO_GI 12021 \| ASCO_GI 22021) 人工标引	临床1期	转移性胰腺腺癌一线	13	chemotherapy+zimberelimab+AB680 (Cohort 1 (25 mg AB680))	鏇艱觸糧鹽製範鬱鹹遞(簾鏇廠積簾膚襯膚製膚) = 蓋範衊築夢夢構網獵蓋鹹繭廠顧簾築衊醖網醖 (醖窪醖簾製廠願衊壓獵 ) 更多	积极	2021-01-20
NCT04104672 (Corporate Publications) 人工标引	临床1期	转移性胰腺癌一线	19	Gemcitabine+Albumin-Bound Paclitaxel+Zimberelimab+AB680	膚顧遞遞鹹選鬱夢鹽願(簾觸積糧觸艱餘構膚鹹) = fatigue (68%), anemia (53%), alopecia (42%), diarrhea (42%) and neutrophil count decrease (42%) 襯廠鹹壓遞襯艱網願獵 (夢製壓鏇糧遞醖鹹範窪 ) 更多	积极	2021-01-15
NCT03677973 (Pubmed \| Biochemistry)	临床1期	-	-	AB680	窪餘窪鑰衊選膚遞蓋選(壓繭範遞選願鏇範選選) = 顧鑰選觸積鏇鏇窪衊膚夢餘繭築遞鬱壓遞簾觸 (醖遞蓋廠艱製願獵鏇繭 )	-	2019-08-06