The goal of this clinical trial is to Assess the Effect of Food on the
Pharmacokinetics (PK) of D3S-001 in Healthy Adult Participants. The main question[s] it aims to answer are:
1. Evaluate the PK of D3S-001 administered in the fasted and fed state in healthy adult participants.
2. Evaluate the safety and tolerability of D3S-001 administered in the fasted and fed state in healthy adult participants.
Potential participants will be screened within 28 days prior to the first dose. Participants will be admitted into the clinical research unit (CRU) on Day -1 and will be confined until end of study (EOS) or until early termination. On Day 1, participants will be randomised to Group 1 or Group 2. Participants will receive Treatment A or Treatment B in each of 2 periods (Periods 1 and 2; Study Days 1 and 4), once under fasted conditions (Treatment A) and once under fed conditions (Treatment B). Each participant will receive both treatments.

开始日期2025-07-11

申办/合作机构

德昇济医药（无锡）有限公司

[+1]

CTR20250246

/ Completed临床1期

一项在健康参与者中评估D3S-001 以两种不同生产工艺制备的胶囊给药后相对生物利用度的随机、开放、双周期交叉1 期临床研究

主要目的：评估健康成年参与者在空腹状态下接受单次口服给药时1× D3S-001.M胶囊100 mg 与1×胶囊100 mg 制剂的药代动力学（PK）特征和相对生物利用度（RBA）。次要目的：评估健康成年参与者空腹单次口服D3S-001.M胶囊100 mg 和D3S-001 胶囊100 mg 制剂后的安全性和耐受性。

开始日期2025-03-03

申办/合作机构

德昇济医药（无锡）有限公司

CTIS2023-508517-16-00

/ Recruiting临床1/2期

A Phase 1/2, Open-label, Dose-escalation, and Dose-expansion Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of D3S-001 Monotherapy or Combination Therapy in Subjects with Advanced Solid Tumors with a KRAS p.G12C Mutation - D3S-001-100

开始日期2024-12-18

申办/合作机构

德昇济医药（无锡）有限公司

100 项与 D3S-001 相关的临床结果

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100 项与 D3S-001 相关的转化医学

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100 项与 D3S-001 相关的专利（医药）

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项与 D3S-001 相关的文献（医药）

2024-09-04·Cancer Discovery

D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities

Article

作者: Lu, Shun ; Rui, Haopeng ; Yu, Mi Ra ; Lu, Jingtao ; Wang, Jia ; Chen, Zhi Jian ; Zhang, Jing ; Cho, Byoung Chul ; Chen, Cheng ; Mok, Tony ; Wang, Wenqian ; Lim, Sun Min

Abstract:

First-generation KRAS G12C inhibitors, such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. One potential explanation for their modest clinical activity is the dynamic “cycling” of KRAS between its guanosine diphosphate (GDP)– and guanosine triphosphate (GTP)–bound states, raising controversy about whether targeting the GDP-bound form can fully block this oncogenic driver. We herein report that D3S-001, a next-generation GDP-bound G12C inhibitor with faster target engagement (TE) kinetics, depletes cellular active KRAS G12C at nanomolar concentrations. In the presence of growth factors, such as epithelial growth factor and hepatocyte growth factor, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust antitumor activity preclinically and translated into promising clinical efficacy in an ongoing phase 1 trial (NCT05410145).Significance: The kinetic study presented in this work unveils, for the first time, that a GDP-bound conformation-selective KRAS G12C inhibitor can potentially deplete cellular active KRAS in the presence of growth factors and offers new insights into the critical features that drive preclinical and clinical efficacy for this class of drugs.

NATURE MEDICINE

D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial

Article

作者: Zhang, Jing ; Zhang, Yanqiao ; Liu, Anwen ; Shen, Yandong ; Zhao, Jun ; Fan, Zifei ; Lee, Myung Ah ; Chen, Zhi Jian ; Song, Zhengbo ; Wang, Hui ; Zhang, Jun ; Lu, Shun ; Loong, Herbert H ; Wang, Jia ; Cho, Byoung Chul ; Park, John J ; Johnson, Melissa L ; Mok, Tony ; Lim, Sun Min ; Li, Ziming ; Chen, Cheng ; Richardson, Gary ; Chen, Qian

D3S-001 is a next-generation KRAS-G12C inhibitor (G12Ci) designed to enhance target engagement efficiency and overcome growth factor-induced nucleotide exchange. D3S-001 was evaluated in a phase 1a dose-escalation study in patients with advanced solid tumors harboring KRAS^G12C mutation (N = 42) and a phase 1b expansion cohort of patients with non-small-cell lung cancer (NSCLC) whose disease progressed after prior G12Ci therapy (N = 20). The primary endpoints were safety and determination of the maximum tolerated dose. Secondary endpoints included pharmacokinetics, confirmed objective response rate (ORR) and disease control rate. D3S-001 demonstrated dose-dependent pharmacokinetics and no dose-limiting toxicities, and the maximum tolerated dose was not reached. Grade 3 treatment-related adverse events were reported in seven patients (16.7%) in the G12Ci-naive dose-escalation cohort and two patients (10.0%) in the G12Ci-pretreated NSCLC expansion cohort. There were no grade 4 or 5 treatment-related adverse events. D3S-001 600 mg was selected as the dose for further investigation based on pharmacokinetics. Confirmed ORR in the G12Ci-naive population was 73.5% overall (25 of 34), and 66.7% (14 of 21), 88.9% (8 of 9) and 75.0% (3 of 4) in patients with NSCLC, colorectal cancer and pancreatic ductal adenocarcinoma, respectively. Among patients with G12Ci-pretreated NSCLC, ORR was 30.0% (6 of 20) and disease control rate was 80.0% (16 of 20). This study demonstrates the safety and tolerability of D3S-001 monotherapy with promising antitumor activity. The phase 1b expansion phase is ongoing. ClinicalTrials.gov identifier: NCT05410145 .

项与 D3S-001 相关的新闻（医药）

2025-08-29

·医药笔记

德昇济：新一代KRAS G12C获FDA授予突破疗法认证

▎Armstrong 2025年8月29日，德昇济宣布其新一代KRAS G12C抑制剂D3S-001获得FDA突破疗法认证和孤儿药资格认证，突破疗法认证是给予KRAS G12C突变、经PD-1和化含铂化疗治疗后进展，但未经KRAS G12C抑制剂治疗的非小细胞肺癌适应症，孤儿药资格是给予KRAS G12C突变的结直肠癌适应症。 D3S-001为德昇济的核心管线，正在快速推进多项临床试验，包括单药二线及以上治疗NSCLC和CRC，以及联合治疗一线治疗NSCLC和CRC。第一代KRAS G12C抑制剂的疗效深度和持久性有限，一种可能的原因是KRAS靶蛋白的GDP-GTP结合状态之间的循环，靶向GDP结合KRAS G12C的药物可能无法完全抑制KRAS G12C。D3S-001则具有全面结合KRAS G12C的能力，同时具有快速靶点募集的特征，且抑制KRAS G12C的能力不受EGF和HGF的影响。今年4月29日，D3S-011一期临床最新数据发表在Nature Medicine期刊上，对KRAS G12C抑制剂初治的晚期实体瘤患者中展现出73.5%（25/34）的ORR，其中NSCLC的ORR为66.7%（14/21），CRC的ORR为88.9%（8/9），胰腺癌的ORR为75.0%（3/4）。此外，对于20名接受过一代KRAS G12C抑制剂治疗后出现疾病进展的NSCLC患者中，D3S-001实现了30.0%的ORR和80.0%的DCR。总结德昇济新一代的KRAS G12C采用了差异化的设计，作用机制上显著优于第一代KRAS G12C抑制剂，并在临床中获得初步POC，一方面疗效更佳突出，另一方面对于一代KRAS G12C耐药的患者仍然表现出优异的疗效潜力。此次获得突破疗法认证，有望进一步加速D3S-001的全球临床开发进度，树立有一个国产创新药的标杆。 Armstrong技术全梳理系列 GPRC5D靶点全梳理； CD40靶点全梳理； CD47靶点全梳理；补体靶向药物技术全梳理；补体药物：眼科治疗的重要方向； Claudin 6靶点全梳理； Claudin 18.2靶点全梳理；靶点冷暖，行业自知；中国大分子新药研发格局；被炮轰的“me too”；佐剂百年史；胰岛素百年传奇； CUSBEA：风雨四十载；中国新药研发的焦虑；中国生物医药企业的研发竞争；中国双抗竞争格局；中国ADC竞争格局；中国双抗技术全梳理；中国ADC技术全梳理； Ambrx技术全梳理； Vir Biotech技术全梳理； Immune-Onc技术全梳理；亘喜生物技术全梳理；康哲药业技术全梳理；科济药业技术全梳理；恺佧生物技术全梳理；同宜医药技术全梳理；百奥赛图技术全梳理；腾盛博药技术全梳理；创胜集团技术全梳理；永泰生物技术全梳理；中国抗体技术全梳理；德琪医药技术全梳理；德琪医药技术全梳理2.0；和铂医药技术全梳理；荣昌生物技术全梳理；再鼎医药技术全梳理；药明生物技术全梳理；恒瑞医药技术全梳理；豪森药业技术全梳理；正大天晴技术全梳理；吉凯基因技术全梳理；基石药业技术全梳理；百济神州技术全梳理；百济神州技术全梳理第2版；信达生物技术全梳理；信达生物技术全梳理第2版；中山康方技术全梳理；复宏汉霖技术全梳理；先声药业技术全梳理；君实生物技术全梳理；嘉和生物技术全梳理；志道生物技术全梳理；道尔生物技术全梳理；尚健生物技术全梳理；康宁杰瑞技术全梳理；科望医药技术全梳理；岸迈生物技术全梳理；礼进生物技术全梳理；康桥资本技术全梳理；余国良的抗体药布局；荃信生物技术全梳理；安源医药技术全梳理；三生国健技术全梳理；仁会生物技术全梳理；乐普生物技术全梳理；同润生物技术全梳理；宜明昂科技术全梳理；派格生物技术全梳理；迈威生物技术全梳理； Momenta技术全梳理； NGM技术全梳理；普米斯生物技术全梳理；普米斯生物技术全梳理2.0；三叶草生物技术全梳理；贝达药业抗体药全梳理；泽璟制药抗体药全梳理；恒瑞医药抗体药全梳理；齐鲁制药抗体药全梳理；石药集团抗体药全梳理；豪森药业抗体药全梳理；华海药业抗体药全梳理；科伦药业抗体药全梳理；百奥泰技术全梳理；凡恩世技术全梳理。

孤儿药突破性疗法抗体药物偶联物快速通道

2025-08-29

·医药观澜

速递丨德昇济医药KRAS G12C抑制剂获FDA授予突破性疗法认定和孤儿药资格

2025年8月29日，德昇济医药（D3 Bio）今日宣布，美国FDA已授予其新一代KRAS G12C抑制剂D3S-001突破性疗法认定，用于治疗既往接受过化疗和免疫治疗、但未接受过KRAS G12C抑制剂治疗的KRAS G12C突变局部晚期或转移性非小细胞肺癌（NSCLC）成人患者。此外，D3S-001还获得FDA授予孤儿药资格，用于治疗KRAS G12C突变局部晚期或转移性结直肠癌（CRC）。突破性疗法认定与孤儿药认定基于一项正在开展的1/2期研究（NCT05410145）的临床数据，该研究旨在评估D3S-001在携带KRAS G12C突变的晚期实体瘤患者中的疗效与安全性。临床试验结果显示，基于实体瘤疗效评价标准（RECIST），D3S-001展现出显著且持久的抗肿瘤疗效，并具有良好的安全性和耐受性。 D3 Bio董事长、创始人兼首席执行官陈之键博士表示： “我们非常高兴D3S-001获得FDA的突破性疗法和孤儿药资格双重认定，这彰显了D3S-001在解决KRAS G12C突变癌症患者重大未满足医疗需求的潜力。这标志着D3S-001作为新一代KRAS G12C抑制剂的创新特性获得了认可。我们期待在监管部门的支持与协作下，将这一创新疗法早日带给患者。” KRAS突变是人类癌症中最常见的致癌驱动基因之一，约25%至30%的肿瘤中存在该突变。其中，KRAS G12C突变约占非小细胞肺癌的12%，在结直肠癌中占比约为3%至4%。携带KRAS G12C突变的癌症患者通常疾病更具侵袭性，对免疫治疗和/或化疗等标准治疗方案反应有限。 D3S-001是一种新一代KRAS G12C抑制剂，具有快速且完全抑制KRAS G12C靶点的能力。D3S-001能够强效、选择性地与RAS G12C变异体的RAS（失活态）共价结合，从而功能性地阻断G12C突变蛋白在RAS（失活态）与RAS（激活态）之间的核苷酸循环。临床前研究显示，D3S-001具有高共价结合效能，在临床相关剂量下可完全抑制KRAS G12C靶点，并具备中枢神经系统（CNS）渗透特性。 D3S-001目前正在开展一项全球2期临床试验，评估其作为单药及联合治疗方案用于携带KRAS G12C突变的晚期实体瘤患者，包括非小细胞肺癌、结直肠癌和其他肿瘤类型。关键发表文献：《D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities》，Cancer Discov. (2024)14(9):1675–1698 《D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial》，Nat Med. 2025 Aug;31(8):2768–2777 D3 Bio是一家全球性生物技术公司，专注于肿瘤与免疫领域新药的发现、开发和注册。公司依托独有的临床洞察力与生物标志物策略，通过其药物发现和开发平台，研发具有临床意义的创新疗法，满足患者的迫切需求。参考资料：[1]D3 Bio新闻稿免责声明：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。

2025-08-28

·PRNewswire

D3 Bio, Inc. Announces FDA Breakthrough Therapy Designation and Orphan Drug Designation for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers

Breakthrough Therapy Designation was granted for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have had prior treatment with platinum-based chemotherapy and anti-PD-(L)1 antibody but have not been previously treated with a KRAS G12C inhibitor Orphan Drug Designation was granted for treatment of colorectal cancer (CRC) harboring KRAS G12C mutant protein. SHANGHAI, Aug. 28, 2025 /PRNewswire/ -- D3 Bio, Inc, a clinical-stage oncology company focuses on discovery and development of precision oncology therapies, today announced that the U.S. Food and Drug Administration (FDA) has granted a Breakthrough Therapy Designation to D3S-001, the company's next generation KRAS G12C-selective inhibitor, for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic NSCLC who have received prior chemotherapy and immunotherapy but have not been previously treated with a KRAS G12C inhibitor. Additionally, D3S-001 has been granted Orphan Drug Designation for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic CRC. The Breakthrough Therapy and Orphan Drug Designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145) evaluating D3S-001 in patients with advanced solid tumors harboring a KRAS G12C mutation. Results from this ongoing clinical trial demonstrated highly compelling and durable efficacy according to RECIST (Response Evaluation Criteria in Solid Tumors) with a favorable safety and tolerability profile. "We are very pleased to receive both Breakthrough Therapy and Orphan Drug Designations from the FDA for D3S-001, which highlights D3S-001's promising potential to address critical unmet needs in patients with KRAS G12C-mutated cancers," said George Chen, Founder and CEO of D3 Bio. "These designations also recognize D3S-001's novel profile as a next-generation KRAS G12C inhibitor. We look forward to bringing this exciting new treatment to patients with support and collaboration from health authorities." KRAS mutations are among the most common oncogenic drivers in human cancers, found in approximately 25 to 30% of all tumors. The KRAS G12C mutation occurs in approximately 12% of NSCLC cases and 3 to 4% of CRC. Patients with KRAS G12C-mutated cancers often have more aggressive disease and limited responses to standard therapies, such as immunotherapy and/or chemotherapy. About D3S-001 D3S-001 is a next-generation KRAS G12C inhibitor designed to achieve rapid and complete KRAS G12C target engagement. D3S-001 potently, selectively, and covalently binds to the oncogenic RAS (Off) form of the RAS G12C variant, functionally abolishing the nucleotide cycling between RAS (Off) and RAS (On) forms of the G12C mutant protein. In preclinical investigations, D3S-001 demonstrated high covalent potency, complete engagement of KRAS G12C at clinically relevant doses and CNS penetration properties. D3S-001 is currently under evaluation as monotherapy and in combination regimens in a Phase II global clinical trial in patients with advanced solid tumors harboring KRAS G12C mutations, including NSCLC, CRC, and other tumor types. Key publications: D3S-001, a KRAS G12C Inhibitor with Rapid Target Engagement Kinetics, Overcomes Nucleotide Cycling, and Demonstrates Robust Preclinical and Clinical Activities. Cancer Discov. (2024)14 (9):1675–1698. D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial. Nat Med. 2025 Aug;31(8):2768-2777. About D3 Bio D3 Bio is a global biotechnology company focused on the discovery, development, and registration of new medicines in oncology and immunology. The company's discovery and development platforms leverage proprietary clinical insight and biomarker strategies to create novel and clinically meaningful therapies for patients in need. D3 Bio's oncology programs target driver mutations or critical immune pathways and are designed to have first-in-class or best-in-class potential. D3 Bio owns global rights for all of its programs. For more information, please visit . Contacts Media Contact: Rui Liu Head, Corporate Affairs [email protected] SOURCE D3 Bio, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

孤儿药临床结果突破性疗法临床2期免疫疗法

100 项与 D3S-001 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
晚期恶性实体瘤	临床2期	美国	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	中国	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	澳大利亚	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	法国	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	德国	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	中国香港	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	意大利	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	韩国	德昇济医药（无锡）有限公司	2022-08-03
晚期恶性实体瘤	临床2期	西班牙	德昇济医药（无锡）有限公司	2022-08-03
KRAS G12C突变的实体瘤	临床2期	美国	德昇济医药（无锡）有限公司	2022-08-03

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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


NCT05410145 (Pubmed) 人工标引	临床1期	KRAS G12C突变的实体瘤 \| 非小细胞肺癌 KRAS G12C	62	D3S-001 (phase 1a；solid tumors)	齋網鹹簾鹹簾鹽夢顧鬱(齋憲鹹夢蓋遞鹽窪醖齋) = 憲鑰膚淵蓋鬱衊築構醖鏇鹽齋淵獵鏇衊膚壓鬱 (製齋鑰築淵製窪糧醖觸 ) 更多	积极	2025-04-29
NCT05410145 (Pubmed) 人工标引	临床1期	KRAS G12C突变的实体瘤 \| 非小细胞肺癌 KRAS G12C	62	D3S-001 (phase 1a；G12Ci-naive NSCLC)	齋襯壓糧觸簾簾繭壓積(襯糧餘顧醖糧餘鬱壓淵) = 鹹齋築觸範膚築蓋鹽獵鬱鏇蓋範鏇廠鏇襯襯憲 (鹹艱蓋齋壓鏇襯糧膚壓 )	积极	2025-04-29
NCT05410145 (D3S-001, AACR2025)	临床2期	KRAS G12C突变非小细胞肺癌 KRAS G12C mutation \| secondary KRAS alterations \| BRAF ... 更多	20	D3S-001 600mg once daily	獵簾簾鹽衊憲蓋醖簾網(顧獵窪鏇蓋糧網艱鹽艱) = 襯範遞餘憲淵衊淵願蓋鹹蓋網壓糧憲積醖壓積 (蓋鑰艱憲構夢觸廠繭鹽 ) 更多	积极	2025-04-29
NCT05410145 (ESMO2024) 人工标引	临床1/2期	KRAS G12C突变的实体瘤二线 \| 一线 KRAS G12C	42	D3S-001 50 mg	壓鏇廠製築選醖願襯鏇(製膚憲鏇選齋顧選憲製) = 鑰鏇夢壓淵餘醖鑰鏇築糧範膚獵積廠衊夢糧醖 (製願觸鬱遞簾膚鹽製積 ) 更多	积极	2024-09-14
NCT05410145 (ESMO2024) 人工标引	临床1/2期	KRAS G12C突变的实体瘤二线 \| 一线 KRAS G12C	42	D3S-001 (G12Ci naïve)	觸餘積繭衊醖夢夢淵膚(範蓋鹹築膚夢選醖膚願) = 餘積膚壓醖醖鹹衊鏇淵願艱鹽鏇齋築觸鬱窪獵 (範範餘鏇網糧選廠構選 ) 更多	积极	2024-09-14
NCT05410145 (D3S-001 FIH, AACR2024) 人工标引	临床1期	KRAS G12C突变的实体瘤 KRAS G12C	41	D3S-001 50mg QD	鹹鑰憲餘鑰鹹襯繭艱簾(膚糧蓋鹹餘觸鹹範餘餘) = 獵齋餘餘鏇糧鑰淵選製壓鏇鹹選壓襯積淵網網 (夢獵構觸窪積網遞蓋醖 ) 更多	积极	2024-04-05