This is a phase 1, open-label, single-dose, parallel-cohort study to determine the pharmacokinetics (PK) of divarasib in healthy participants and participants with varying degrees of hepatic impairment, as defined by Child-Pugh classification.

开始日期2024-12-23

申办/合作机构

Genentech, Inc.

NCT06690138

/ Recruiting临床1期

A Phase 1, Open-Label, Single-Dose, Two-Period, Fixed Sequence, Crossover Study to Determine the Effect of Itraconazole on the Pharmacokinetics of Divarasib in Healthy Subjects

This is a Phase 1, open-label, two-period, fixed sequence drug-drug interaction study to evaluate the impact of multiple doses of Itraconazole on the pharmacokinetics (PK) and safety of Divarasib in healthy participants.

开始日期2024-11-15

申办/合作机构

Genentech, Inc.

NCT06677957

/ Completed临床1期

A Phase I, Open-Label, Two-Period, One-Sequence, Crossover Study in Healthy Subjects to Evaluate the Clinical Drug-Drug Interaction of Divarasib With Probe Substrates of P-Glycoprotein (Digoxin) and Breast Cancer Resistance Protein (Rosuvastatin)

This is a Phase 1, open-label, two-period, one-sequence, crossover drug-drug interaction study to assess the P-gp and BCRP inhibition potential of divarasib using digoxin and rosuvastatin as probe substrates, respectively, in healthy participants.

开始日期2024-11-06

申办/合作机构

Genentech, Inc.

100 项与 Divarasib 相关的临床结果

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100 项与 Divarasib 相关的转化医学

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100 项与 Divarasib 相关的专利（医药）

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项与 Divarasib 相关的文献（医药）

2024-11-25·Future Oncology

An updated overview of K-RAS G12C inhibitors in advanced stage non-small cell lung cancer

Review

作者: Ceylan, Furkan ; Nahit Sendur, Mehmet Ali ; Unal, Ahmet Arda ; Tenekeci, Ates Kutay

The discovery of KRAS mutations, particularly the KRASG12C variant, has been a milestone in understanding the molecular underpinnings of non-small cell lung cancer (NSCLC). These mutations are associated with aggressive tumor behavior and resistance to conventional therapies, highlighting the urgent need for targeted interventions. In this comprehensive review, we analyze the advancements in KRAS G12C inhibitors for the treatment of non-small cell lung cancer. Literature search is made from PubMed, Medline ASCO and ESMO Annual Meetings abstracts by using the following search keywords: "sotorasib", "adagrasib", "divarasib" and "KRAS G12C inhibitors." The last search was on 5 June 2024. This review highlights the importance of pharmacokinetics, pharmacodynamics and potential adverse effects for treating individual patients and ensuring the best outcomes. Additionally, the review discusses research identifying biomarkers that can predict therapy responses and mentions the combination strategies to overcome resistance. Results of the studies and ongoing clinical trials are also briefly summarized in this review. KRASG12C inhibitors sotorasib, adagrasib and the newer divarasib, has revolutionized treating patients harboring this mutation. Ongoing studies and future clinical trials will refine our understandings with the ultimate goal of improving survival and quality of life for patients with this challenging disease.

2024-11-06·JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY

High Resolution Ion Mobility Enables the Structural Characterization of Atropisomers of GDC-6036, a KRAS G12C Covalent Inhibitor

Article

作者: Crittenden, Christopher M. ; Napolitano, José G. ; Russell, David J. ; Thomas, Rekha ; Ochoa, Jessica L. ; Varona, Marcelino ; Dobson, Daniel P.

GDC-6036 is a covalent KRAS G12C inhibitor that demonstrates high potency and selectivity. Structurally, GDC-6036 consists of several motifs that make the analytical characterization of this molecule challenging, including a highly basic pyrrolidine motif bonded to a quinazoline ring via an ether bond and an atropisomeric carbon-carbon bond between functionalized pyridine and quinazoline groups. Structurally, the desired atropisomer was synthesized via an atroposelective Negishi coupling with very high yield. However, having a direct way to analyze and confirm the presence of the atropisomeric species remained challenging in routine analytical workflows. In this study, both variable temperature nuclear magnetic resonance (VT-NMR) and two different approaches of in-line ion mobility coupled to liquid chromatography mass spectrometry (LC-MS) workflows were evaluated for the characterization of GDC-6036 and its undesired atropisomer (Compound B) to support synthetic route development. Briefly, both VT-NMR and traveling wave ion mobility spectrometry (TWIMS) enabled by structures for lossless ion manipulation (SLIM) technology coupled to high resolution MS (HRMS) are able to elucidate the structures of the atropisomers in a complex mixture. Drift tube IMS (DTIMS) was also evaluated, but lacked the resolving power to demonstrate separation between the two species in a mixture, but did show slight differences in their arrival times when multiplexed and injected separately. The determined resolving power (R_p) by multiplexing the ions via DTIMS was 67.3 and 60.5 for GDC-6036 and Compound B, respectively, while the two peak resolving power (R_pp) was determined to be 0.41, indicating inadequate resolution between the two species. Alternatively, the SLIM-IM studies showed R_p of 103.8 and 99.4, with a R_pp of 2.64, indicating good separation between the atropisomers. Furthermore, the CCS/z for GDC-6036 and Compound B was determined to be 231.2 Å²/z and 235.0 Å²/z, respectively. Quantitative experiments demonstrate linearity (R² >0.99) for both GDC-6036 and Compound B while maintaining separation via SLIM-IM. Spike recoveries of one atropisomer relative to the other yielded strong recoveries (98.7% to 102.5%) while maintaining reproducibility (<7% RSD). The study herein describes the analytical process for evaluating new technologies and strategies for implementation in routine biopharmaceutical characterization workflows.

2024-09-03·CLINICAL CANCER RESEARCH

Circulating Tumor DNA Dynamics Reveal KRAS G12C Mutation Heterogeneity and Response to Treatment with the KRAS G12C Inhibitor Divarasib in Solid Tumors

Article

作者: Jun, Tomi ; Shi, Zhen ; Desai, Jayesh ; Aimi, Junko ; Dharia, Neekesh V. ; Assaf, Zoe J. ; Schutzman, Jennifer L. ; LoRusso, Patricia ; Yau, Kenneth K. ; Sivakumar, Smruthy ; Sacher, Adrian ; Chang, Julie ; Choi, Yoonha ; Royer-Joo, Stephanie ; Montesion, Meagan

Abstract:

Purpose::

To inform prognosis, treatment response, disease biology, and KRAS G12C mutation heterogeneity, we conducted exploratory circulating tumor DNA (ctDNA) profiling on 134 patients with solid tumors harboring a KRAS G12C mutation treated with single-agent divarasib (GDC-6036) in a phase 1 study.

Experimental Design::

Plasma samples were collected for serial ctDNA profiling at baseline (cycle 1 day 1 prior to treatment) and multiple on-treatment time points (cycle 1 day 15 and cycle 3 day 1).

Results::

KRAS G12C ctDNA was detectable from plasma samples in 72.9% (43/59) and 92.6% (50/54) of patients with non–small cell lung cancer and colorectal cancer, respectively, the majority of whom were eligible for study participation based on a local test detecting the KRAS G12C mutation in tumor tissue. Baseline ctDNA tumor fraction was associated with tumor type, disease burden, and metastatic sites. A decline in ctDNA level was observed as early as cycle 1 day 15. Serial assessment showed a decline in ctDNA tumor fraction associated with response and progression-free survival. Except for a few cases of KRAS G12C sub-clonality, on-treatment changes in KRAS G12C variant allele frequency mirrored changes in the overall ctDNA tumor fraction.

Conclusions::

Across tumor types, the KRAS G12C mutation likely represents a truncal mutation in the majority of patients. Rapid and deep decline in ctDNA tumor fraction was observed in patients responding to divarasib treatment. Early on-treatment dynamics of ctDNA were associated with patient outcomes and tumor response to divarasib treatment.

项与 Divarasib 相关的新闻（医药）

2024-12-28

·药明康德

蛋白降解、AI火热，首款PROTAC呼之欲出 | 2024攻克难以成药靶点动向

▎药明康德内容团队编辑共价剂、别构剂和诱导接近分子等创新小分子药物技术的进展，使产业得以超越“锁-钥原理”来靶向以往被认为“难以成药”的靶点。 2024年，这一领域依然风起云涌，诸多重磅新闻正在预示小分子药物的新篇章：有助于加快难以成药靶点新药研发的AI解决方案摘得诺奖桂冠，多家新锐正在采用AI技术解决成药难题。针对难以成药靶点的新颖技术纷纷被大药企看好，拜耳就针对凝聚体的药物达成超4亿美元合作；耶鲁大学蛋白降解先驱Craig Crews教授创立的Arvinas与诺华达成超10亿美元合作；分子胶领域多笔高额合作，达歌生物与武田达成总额约12亿美元合作，SEED Therapeutics与卫材达成潜在总额15亿美元的合作，Monte Rosa Therapeutics与诺华达成潜在总额超过22亿美元的合作，Neomorph今年先后与诺和诺德、渤健达成合作，潜在总额超过29亿美元…… 而2025年第一季度，我们还有望迎来蛋白降解疗法研发的重要里程碑，潜在首款PROTAC疗法的3期临床研究数据揭晓在即。在这篇文章中，药明康德内容团队将为大家回顾2024年产业针对难以成药靶点或相关技术的新药获批和研发进展趋势。扫描文中二维码或点击文末“阅读原文”可申请获得完整报告，包括已获批疗法及2025即将获批疗法盘点、大型药企管线列表、融资新锐介绍等详尽信息。 ▲长按扫描二维码或点击文末“阅读原文/Read more”，即可填写问卷，申请获取攻克难以成药靶点研发进展完整报告新型小分子获批速度稳健，2024年再迎两款KRAS靶向药近3年来，全球范围内已有至少15款基于共价/别构/诱导接近的新颖机制开发的创新小分子首次获批，2024年也保持了稳健的获批速度。2024年4款基于共价机制的创新药在全球首次获批，包括2款治疗非小细胞肺癌（NSCLC）的KRAS共价抑制剂；此外，1款基于蛋白质-蛋白质相互作用的创新药revumenib问世，针对menin-KMT2A相互作用来抑制menin，用于治疗KMT2A易位的复发/难治性急性白血病，revumenib也是治疗此类患者群体的首款获批menin抑制剂。 ▲近3年全球首次获批的基于共价/别构/诱导接近分子机制开发的疗法（药明康德内容团队制图，数据截至2024年12月20日）基于当前研发与监管审评进展公开信息，3款共价抑制剂有望在2025年迎来首次批准：加科思研发的KRAS抑制剂戈来雷塞，用于治疗局部晚期或转移性NSCLC的上市申请已于2024年5月获中国国家药品监督管理局（NMPA）受理并纳入优先审评程序；赛诺菲旗下的两款BTK抑制剂，分别为治疗免疫性血小板减少症的rilzabrutinib和治疗多发性硬化的tolebrutinib，均已在3期试验中取得积极结果，正在准备向监管机构递交上市申请。 36家新锐完成早期融资：蛋白降解新模式、AI受青睐 2024年，共36家致力于攻克难以成药靶点或专注于相关技术的新锐获得总额近16亿美元的早期投融资。从技术特点来看，开发共价剂（多为抗癌疗法）、别构剂（大多聚焦神经系统疾病）的新锐占据半壁江山（17家），其中不乏新颖的共价机制，如结合非自然界氨基酸生成能与靶点共价结合的治疗性蛋白。专注于蛋白降解或调节蛋白-蛋白相互作用疗法的新锐持续涌现（12家），且不乏新模式。例如，Pinetree Therapeutics开发多特异性靶向蛋白质降解剂，A轮融资1700万美元，且与阿斯利康达成总额超5亿美元合作；Draupnir Bio和Booster Therapeutics基于溶酶体机制开发蛋白降解剂，种子轮融资逾千万美元；Firefly Bio由诺贝尔化学奖得主Carolyn Bertozzi教授联合创立，开发蛋白降解剂-抗体偶联药物（DAC），获得9400万美元A轮融资；Craig Crews教授创立的Halda Therapeutics开发基于诱导接近机制的RIPTAC（调节诱导接近靶向嵌合体）分子，完成1.26亿美元B轮融资。Halda自成立以来就与药明康德长期合作。药明康德针对蛋白降解疗法的研发搭建了完善的一体化赋能平台，服务了全球蛋白降解疗法开发领域66%的公司，助力前沿科学发现转化为创新疗法。也有多家新锐开发大环分子。与抗体等生物制品相比，大环分子的分子量更小，可以口服使用，并且可以穿过细胞膜靶向细胞内的蛋白。而与传统小分子相比，环状结构让大环分子更容易影响蛋白质之间的相互作用，从而靶向传统小分子药物和线性多肽难于靶向的靶点。 AI也是今年的一大热点。多家新锐基于AI平台攻克难成药靶点，加速疗法研发，包括由蛋白设计先驱David Baker教授联合创立的两家公司：Vilya基于AI平台从头设计大环分子，完成2100万A轮扩展融资，Archon Biosciences设计抗体笼，这类分子由抗体和AI生成蛋白结构域组成，该公司完成2000万美元种子轮融资。大药企临床管线：潜在首款PROTAC即将冲线，新一代KRAS靶向疗法涌现针对难以成药靶点或基于相关技术，全球20家大型药企已布局36款临床在研疗法。这些疗法中，近一半已处于后期研发阶段或正在拓展适应症。 ▲全球20家大型药企针对难以成药靶点或采用相关机制开发的管线分布；扫描文中二维码可申请获取完整管线列表（药明康德内容团队制图，数据来源为各药企公开信息，截至2024年12月，20家大型药企参考行业媒体Fierce Pharma 2024年榜单）其中广受关注的是潜在首款PROTAC疗法vepdegestrant。辉瑞与Arvinas在2021年就这款疗法达成超20亿美元研发合作，期望它能成为雌激素受体阳性（ER+）乳腺癌患者的支柱性疗法。两家公司预计在2025年第一季度公布其作为乳腺癌单药疗法的3期试验顶线数据。目前，vepdegestrant联合CDK4/6抑制剂的临床研究也在推进，已有两项1b期临床试验显示积极结果。其他处于3期临床开发阶段的在研疗法还包括：治疗NSCLC的2款KRAS抑制剂olomorasib和divarasib，治疗银屑病的TYK2抑制剂zasocitinib，治疗淋巴瘤、靶向Ikaros/Aiolos的分子胶golcadomide，治疗乳腺癌的多款雌激素受体降解剂，以及针对BTK、EGFR、HER2等经典靶点的共价抑制剂等。如前文所述，赛诺菲旗下2款BTK共价抑制剂均即将迈入监管申请阶段。多样化的技术正在解决更多靶点的成药性，如Helios、WRN、CK1α等靶点。新一代KRAS靶向疗法也是热门研发方向，如泛KRAS抑制剂、采用非共价机制的KRAS抑制剂。结语 2024年，解锁难以成药靶点的技术持续为患者带来创新疗法，资本市场继续扶植前沿技术的发展，尤其是在蛋白降解领域，在PROTAC和分子胶之外，更多异双功能分子等新颖技术的涌现正在拓展成药边界，而AI从头设计蛋白、抗体、环肽等药物则为加速新药研发注入强大推动力。我们坚信，攻克难以成药靶点的研发浪潮势不可挡，首款PROTAC疗法呼之欲出，更多靶点的突破也指日可待，将造福全球更多患者。 ▲长按扫描二维码或点击文末“阅读原文/Read more”，即可填写问卷，申请获取攻克难以成药靶点研发进展完整报告 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。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：本文来自药明康德内容团队，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

优先审批临床3期蛋白降解靶向嵌合体上市批准

2024-11-08

·医药魔方Info

国产第2款：正大天晴KRAS G12C抑制剂获批上市

11月8日，国家药监局官网显示，益方生物与正大天晴合作开发的格索雷塞片（曾用名：格舒瑞昔片，商品名：安方宁）获批上市，用于治疗至少接受过一种系统性治疗的鼠类肉瘤病毒癌基因（KRAS）G12C突变型的晚期非小细胞肺癌（NSCLC）成人患者。该产品为继信达生物/劲方医药的氟泽雷塞后，第2款获批上市的国产KRAS G12C抑制剂。格索雷塞可通过共价结合不可逆地抑制KRAS G12C，使之处于无活性的GDP结合状态。目前，该产品正在开展针对KRAS G12C突变的非小细胞肺癌、结直肠癌等多种癌症的临床试验。一项单臂、多中心I/II期研究结果显示，格索雷塞在携带KRAS G12C突变的非小细胞肺癌患者中具有良好的安全性和抗肿瘤活性。据益方生物公告，截至2022年9月12日，在接受治疗的79例患者中，75例患者（94.9%）报告了治疗相关不良事件（TRAE）。30例（38.0%）患者报告了3级或4级不良事件（AE），其中大多数AE可控可管理，仅有1例患者因AE永久停药。在所有剂量水平下格索雷塞的耐受性佳，显示出良好的安全性。同时，79例患者中有30例评估为部分缓解（PR），38例为疾病稳定（SD），确认的客观缓解率（ORR）为40.5%（95% Cl: 29.3–52.6），疾病控制率（DCR）为91.9%（95% Cl: 83.2–97.0），无进展生存期（PFS）达到8.2个月。 2023年8月，正大天晴与益方生物就格索雷塞达成一项合作协议，获得该药物在中国大陆地区的独占性开发、注册、生产和商业化权益。正大天晴将向益方生物支付最高不超过人民币5.5亿元的首付款（2.6亿）及里程碑付款（2.9亿），并按年净销售额支付分层特许权使用费。目前，全球共有4款KRAS G12C抑制剂获批上市，分别为sotorasib（安进）、adagrasib（Mirati）、氟泽雷塞和格索雷塞，其中仅氟泽雷塞和格索雷塞在中国获批上市。此外，加科思的格来雷塞也已提交上市申请。除此之外，还有5款KRAS G12C抑制剂处于III期阶段，包括LY3537982（礼来）、HJ891（华健未来）、MK-1084（默沙东）、divarasib（罗氏）、JMKX001899（济民可信原研）。 Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

上市批准临床3期引进/卖出

2024-10-17

·EndPoints

FDA delays colorectal cancer decision for Amgen's Lumakras, a setback in race with Bristol Myers

The FDA has pushed back its decision deadline to move Amgen’s KRAS inhibitor Lumakras into metastatic colorectal cancer to January, the company told Endpoints News . The regulator was supposed to decide Thursday whether to approve the drug in combination with Amgen’s EGFR drug Vectibix for chemorefractory metastatic colorectal cancer patients who have a KRAS G12C mutation. After Endpoints sent Amgen questions about the status of the review, the company said the new deadline for action is three months from now, on Jan. 17, 2025. Amgen said the delay was to “allow additional time for review of supplemental data recently submitted to the agency.” Lumakras is currently approved under the accelerated pathway for non-small cell lung cancer. Another KRAS inhibitor, Bristol Myers Squibb’s Krazati, is also approved under the accelerated pathway in both lung cancer and colorectal cancer. The colorectal market is a large one, though KRAS G12C mutations make up just 3% to 4% of metastatic cases. Cancers of the colon and rectum are projected to make up 8% of all new cancer diagnoses in 2024, according to the National Cancer Institute . That places those cancers just behind breast, prostate and lung cancers. The FDA cleared Bristol Myers’ Krazati for use with Eli Lilly’s Erbitux in June for previously treated locally advanced or metastatic colorectal cancer patients. Amgen applied for approval in metastatic colorectal cancer with results from the CodeBreaK 300 study, which showed that a 960 mg dose of the drug resulted in a 30.2% response rate. However, it didn’t improve overall survival, according to data presented in June , though Amgen said the study wasn’t powered to show a statistically significant improvement in survival. Lumakras was the first KRAS inhibitor to win regulatory approval in 2021. It marked a major medical breakthrough. Researchers have long known that KRAS mutations drive cancer, but hadn’t been able to treat them in a targeted fashion. The efficacy of the drugs, though, has been modest. In lung cancer, the FDA declined to convert Lumakras’ accelerated approval to a full one in December, citing concerns around the reliability of the pivotal trial data and noting that the median progression-free survival benefit could be less than what Amgen claimed — and potentially as little as five days. Commercially, sales of Lumakras have been tepid, generating $167 million for the first half of the year. Roche is developing its own KRAS inhibitor divarasib, which it is studying in a Phase 3 trial head-to-head against Krazati and Lumakras in second-line lung cancer and Phase 1/1b for colorectal cancer. Other companies, including Revolution Medicines, are developing RAS inhibitors that they hope can be more effective and go beyond the single mutation G12C, which could help treat more patients.

上市批准临床3期加速审批临床结果

100 项与 Divarasib 相关的药物交易

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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
晚期非小细胞肺癌	临床3期	中国	F. Hoffmann-La Roche Ltd.	2022-11-07
晚期非小细胞肺癌	临床3期	中国	罗氏（中国）投资有限公司	2022-11-07
晚期非小细胞肺癌	临床3期	澳大利亚	罗氏（中国）投资有限公司	2022-11-07
晚期非小细胞肺癌	临床3期	澳大利亚	F. Hoffmann-La Roche Ltd.	2022-11-07
KRAS G12C突变非小细胞肺癌	临床3期	中国	罗氏（中国）投资有限公司	2022-11-07
KRAS G12C突变非小细胞肺癌	临床3期	中国	F. Hoffmann-La Roche Ltd.	2022-11-07
KRAS G12C突变非小细胞肺癌	临床3期	澳大利亚	罗氏（中国）投资有限公司	2022-11-07
KRAS G12C突变非小细胞肺癌	临床3期	澳大利亚	F. Hoffmann-La Roche Ltd.	2022-11-07
转移性非小细胞肺癌	临床3期	加拿大	Hoffmann-La Roche, Inc.	2017-09-22
转移性非小细胞肺癌	临床3期	以色列	Hoffmann-La Roche, Inc.	2017-09-22

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临床结果

适应症

分期

评价

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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


NCT04449874 (WCLC2024) 人工标引	临床1期	KRAS G12C突变阳性肿瘤 KRAS G12C	104	Divarasib 50-400 mg	壓製襯窪構選醖壓積憲(艱範壓網壓醖醖齋遞餘) = 鑰膚糧齋顧鏇鹽網積膚範繭齋範餘齋遞築遞觸 (顧衊積鹹簾簾鏇鏇蓋鏇 ) 更多	积极	2024-09-09
NCT04449874 (WCLC2024) 人工标引	临床1期	KRAS G12C突变阳性肿瘤 KRAS G12C	104	Divarasib+atezolizumab	壓製襯窪構選醖壓積憲(艱範壓網壓醖醖齋遞餘) = 積艱糧觸製願糧窪製廠範繭齋範餘齋遞築遞觸 (顧衊積鹹簾簾鏇鏇蓋鏇 ) 更多	积极	2024-09-09
WCLC2024	临床3期	转移性非小细胞肺癌 KRAS G12C+	-	Divarasib	網鑰觸餘窪範範構憲願(範衊膚範糧醖餘餘蓋築) = 構餘範餘膚簾網遞網觸窪夢築製夢簾築鹹襯窪 (鬱鏇選簾簾蓋繭鏇鑰夢, 39.6 ~ 72.2) 更多	-	2024-09-09
NCT04449874 (Literature) 人工标引	临床1期	KRAS G12C突变的实体瘤 KRAS G12C Mutation	137	GDC-6036	-	积极	2023-08-24
NCT04449874 (Literature) 人工标引	临床1期	KRAS G12C突变的实体瘤 KRAS G12C Mutation	137	GDC-6036 (NSCLC)	積構艱鹹繭膚遞糧構醖(鑰願醖繭齋齋構簾網簾) = 顧繭選廠齋蓋艱簾壓構鹹鹹繭艱壓衊壓遞窪觸 (願齋願範繭醖衊繭網蓋, 39.9 ~ 66.7) 更多	积极	2023-08-24
NCT04449874 (GO42144, NEWS) 人工标引	临床1期	非小细胞肺癌 \| 结直肠癌 \| KRAS G12C突变阳性肿瘤 KRAS G12C Positive	137	Divarasib	膚壓鏇鑰艱壓範衊築鏇(築顧壓網構衊鏇蓋鏇夢) = 積網齋範艱窪齋繭糧製醖壓壓製簾簾糧鏇廠網 (簾鑰築繭齋憲範鹹鏇壓 ) 更多	积极	2023-08-24
NCT04449874 (GO42144, NEWS) 人工标引	临床1期	非小细胞肺癌 \| 结直肠癌 \| KRAS G12C突变阳性肿瘤 KRAS G12C Positive	137	Divarasib (non-small-cell lung cancer)	獵膚顧獵獵觸窪顧遞繭(觸築糧獵蓋廠鬱簾築鹽) = 齋築繭醖鹽襯築鑰壓鹹願製糧壓衊夢構觸觸壓 (願夢簾憲窪襯簾構顧獵 ) 更多	积极	2023-08-24
NCT04449874 (Pubmed)	临床1期	转移性实体瘤 \| 晚期恶性实体瘤 \| 非小细胞肺癌 ... 更多	137	Divarasib	鏇願鏇製鹽範鹽憲淵廠(鏇襯膚夢蓋顧觸憲網簾) = 淵顧憲蓋獵膚醖襯衊顧膚網廠遞窪餘網獵鑰廠 (艱觸壓廠願壓膚製窪餘, 39.9 ~ 66.7)	-	2023-08-24
NCT04449874 (AACR2023) 人工标引	临床1期	结直肠癌 KRAS G12C Mutation	29	GDC-6036+cetuximab	艱獵憲蓋蓋顧製觸鬱獵(餘膚廠顧鹹製鹹鑰顧衊) = 簾糧艱顧鏇壓衊夢廠餘願餘鑰鏇觸鹹鹽構夢膚 (壓遞齋壓範築淵壓夢顧 ) 更多	积极	2023-04-14
NCT04449874 (ESMO2022)	临床1期	KRAS G12C突变的实体瘤	14	GDC-6036	網壓襯鹹壓廠顧壓夢鏇(壓遞獵夢廠膚艱構襯觸) = 糧顧齋遞膚憲顧願鏇廠範膚鏇醖築鏇選夢淵築 (膚鬱顧顧鏇壓夢製觸壓 ) 更多	-	2022-09-12
NCT04449874 (ESMO2022) 人工标引	临床1期	结直肠癌 KRAS G12C mutation	43	GDC-6036	餘餘淵觸膚願鹹膚觸廠(蓋築蓋醖構襯鹹網範壓) = The most frequent GDC-6036-related AEs (≥ 10% pts) were nausea, diarrhea, vomiting, dyspepsia, fatigue, and decreased appetite 願簾構範餘鹽壓壓艱廠 (糧觸鹽餘網顧鹹製夢壓 ) 更多	积极	2022-09-10