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更新于：2026-07-31
Divarasib
更新于：2026-07-31
概要
基本信息
药物类型 小分子化药 |
别名 Divarasib Adipate、GDC-6036、RG 6330 + [5] |
作用方式 抑制剂 |
作用机制 KRAS G12C抑制剂(KRAS G12C突变抑制剂) |
非在研适应症- |
原研机构 |
非在研机构- |
最高研发阶段临床3期 |
首次获批日期- |
最高研发阶段(中国)临床3期 |
特殊审评突破性疗法 (美国)、孤儿药 (美国)、孤儿药 (日本) |
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结构/序列
分子式C29H32ClF4N7O2 |
InChIKeyZRBPIAWWRPFDPY-IRXDYDNUSA-N |
CAS号2417917-17-8 |
关联
19
项与 Divarasib 相关的临床试验NCT07541170
A Phase III, Randomized, Open-label Study Evaluating the Efficacy and Safety of Divarasib Compared With Investigator's Choice of Immunotherapy or Observation in Patients With Resected Stage II-III KRAS G12C-Positive Non-small Cell Lung Cancer
NCT06793215
A Phase III, Randomized, Open-Label Study Evaluating the Efficacy and Safety of Divarasib and Pembrolizumab Versus Pembrolizumab and Pemetrexed and Carboplatin or Cisplatin in Patients With Previously Untreated, KRAS G12C-Mutated, Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer
NCT06835465
A Phase 1, Open-Label, Single-Dose, Two-Period, Fixed Sequence, Crossover Study to Determine the Effect of Rifampin on the Pharmacokinetics of Divarasib in Healthy Subjects
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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40
项与 Divarasib 相关的文献（医药）2026-05-28CANCER INVESTIGATION
A Systematic Review of the Efficacy of KRAS p.G12C Inhibitors in Metastatic Colorectal Cancer: The Current State of Science
Review
作者: Baytar, Doga Kahramangil ; Boby, Jeffrey Mathew ; Benny, Jame Mathew ; Peniche, Paola Zinser ; Sahin, Ibrahim Halil ; Ilerhunmwuwa, Nosakhare
BACKGROUND:
KRAS p.G12C (c.34G > T) inhibitors have been reported to have varying survival outcomes in CRC patients across studies. Hence, our review aimed to provide a comprehensive understanding of the efficacy and safety of these agents among the CRC population.
METHODS:
Major databases, including but not limited to PubMed and Ovid, were searched for original clinical trials assessing the efficacy or safety of KRAS p.G12C (c.34G > T) inhibitors in CRC patients through May 2025. Studies with non-G12C KRAS-mutated populations were excluded. Data on patient demographics and various variables, including but not limited to OS, PFS, and TRAE incidence, were extracted from included studies.
RESULTS:
Our systematic review analyzed 18 trials and 1011 patients. Adagrasib monotherapy yielded a median PFS of 4.4-5.6 months, an OS of 10-19.8 months, and an ORR of 19-23%, while its combination with cetuximab reported a PFS of 6.9 months, an OS of 13.4-15.9 months and an ORR of 34-46%. Sotorasib monotherapy (960 mg) reported a PFS of 4 months, an OS of 10.6 months, and an ORR of 9.7. When combined with panitumumab, 960 mg sotorasib demonstrated better results with a PFS of 5.6-5.7 months, OS of 15.2 months and an ORR of 12.5-30%. Similarly, divarasib monotherapy led to a PFS of 5.6-6.9 months and an ORR of 20%, while its combination with cetuximab resulted in a PFS of 8.1 months and an ORR of 62.5%. Combination therapy of olomorasib and MK-1084, which are new-generation KRAS p.G12C (c.34G > T) inhibitors, with cetuximab also demonstrated highly promising efficacy with ORR of 38-44% and 50%, respectively. Olomorasib with cetuximab also showed a PFS of 6.6-7.5 months. Nausea, vomiting, diarrhea, rash, and increased AST/ALT were the most common TRAEs.
CONCLUSIONS:
Initial results of KRAS-G12C inhibitors appear highly promising when they are combined with anti-EGFR therapy compared to historical therapeutic agents indicated for patients with chemotherapy-refractory CRC. Encouraging benefits warrant frontline trials with these novel therapeutics.
2026-03-12JOURNAL OF MEDICINAL CHEMISTRY
Discovery and Optimization of a Potent, Efficacious, and Brain-Penetrant Inhibitor of KRAS G12C
Article
作者: Tran, John C. ; Yen, Chun-Wan ; Evangelista, Marie ; Hu, Dennis ; de la Cruz, Cecile C. ; Wong, Susan ; Mroue, Rana ; Shao, Cheng ; Wei, Binqing ; Oh, Angela ; Salphati, Laurent ; Purkey, Hans E. ; Hunsaker, Thomas ; Endres, Nicholas F. ; Izrayelit, Yevgeniy ; Gustafson, Amy ; La, Hank ; Merchant, Mark ; Chan, Emily ; Wang, Yanguang ; Chan, Connie ; Hsu, Peter ; Saenz-Lopez Larrocha, Pablo ; Wang, Weiru ; Landry, Matthew L. ; Zhou, Yuhui ; Beresini, Maureen ; Mao, Jialin ; Lian, Qihui ; Malhotra, Sushant ; Siu, Michael ; Plise, Emile ; Heffron, Timothy P.
Mutant KRAS is highly prevalent in human cancer and has been actively pursued as a target for drug discovery. Much progress has been made in drugging KRAS G12C, owing to the ability of inhibitors to covalently target its oncogenic cysteine mutation at codon 12. A number of KRAS G12C inhibitors have advanced to clinical development and are being investigated for the treatment of a variety of solid tumors. Notably, many patients with KRAS G12C-positive non-small cell lung cancer develop brain metastases. Herein, we report the discovery and development of a brain-penetrant inhibitor of KRAS G12C using divarasib as a starting point. Optimization efforts focused on reducing molecular weight and topological polar surface area as well as shielding of hydrogen bond donors. In this manner, active transport by both P-gp and breast cancer resistance protein (BCRP) was attenuated, and high exposure in rodent brain tissue was achieved.
2026-03-12JOURNAL OF MEDICINAL CHEMISTRY
Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C
Article
作者: Ishisoko, Noriko ; Liu, Liling ; Saabye, Matt ; Boudreau, Aaron ; Evangelista, Marie ; Landry, Matthew L. ; Wei, Wentao ; Endres, Nicholas F. ; Miller, Sarah ; Malhotra, Sushant ; Zhou, Yuhui ; Zang, Richard ; Garner, Thomas ; Oh, Angela ; Mao, Jialin ; Zhang, Chenghong ; Yuen, Po-Wai ; Zhu, Xiaoyu ; Kellar, Terry ; Jiang, Fan ; Quinn, John G. ; Yu, Kebing ; Liu, Wendy ; Mroue, Rana ; Tran, John C. ; Ma, Taylur P. ; Izrayelit, Yevgeniy ; Merchant, Mark ; Nguyen, Lan K. ; Wang, Weiru ; Kiefer, James R. ; Beresini, Maureen ; Ye, Xin ; Rudolph, Joachim ; Bronner, Sarah M. ; Lardy, Matthew ; Purkey, Hans E. ; Labadie, Sharada ; Gerosa, Luca ; Plise, Emile ; Hunsaker, Thomas ; Cyr, Patrick ; Do, Steven ; Yu, Christine ; Wong, Susan ; Shao, Cheng ; Lian, Qihui ; Sellers, Benjamin D. ; Terrett, Jack A. ; Wang, Yanguang ; Chan, Emily ; La, Hank
KRAS G12C is one of the most prevalent oncogenic mutations in nonsmall cell lung cancer. Herein we describe the discovery and optimization of divarasib (GDC-6036), an orally available, highly potent, and selective covalent KRAS G12C inhibitor. We demonstrate a significant noncovalent binding component of divarasib that contributes to its potency and rapid kinetics. Divarasib has greater potency and kinetics of alkylation compared with other KRAS G12C inhibitors in vitro and shows robust tumor growth inhibition in multiple KRAS G12C-positive cell lines.
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, 后查看更多信息
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| 适应症 | 最高研发状态 | 国家/地区 | 公司 | 日期 |
|---|---|---|---|---|
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 美国 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 中国 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 日本 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 阿根廷 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 澳大利亚 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 比利时 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 巴西 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 加拿大 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 丹麦 | 2025-10-24 | |
| KRAS G12C突变非鳞状非小细胞肺癌 | 临床3期 | 法国 | 2025-10-24 |
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临床结果
临床结果
适应症
分期
评价
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临床2期 | 新辅助 KRAS G12C+ | 15 | Neoadjuvant divarasib | 餘壓繭壓齋窪醖選願鬱(窪構鏇艱衊廠淵襯蓋鹹) = The most common adverse events (AEs; ≥20% pts) during the neoadjuvant phase were nausea (80%), diarrhoea (73%), constipation (33%), vomiting (27%) and fatigue (20%); most were Gr 1-2. No AEs of aspartate aminotransferase or alanine aminotransferase increase occurred. No pts discontinued neoadjuvant treatment due to AEs. 憲獵齋餘獵夢齋簾餘憲 (衊網遞膚網窪膚淵遞繭 ) 更多 | 积极 | 2026-03-25 | |
临床1期 | 32 | 窪蓋鹽夢蓋淵顧積壓醖(餘膚廠齋積壓艱獵積膚) = >10% 鑰顧獵鏇糧夢糧衊鑰醖 (鹽齋鏇製壓鹹憲顧選鹽 ) 更多 | 积极 | 2025-10-17 | |||
临床1期 | KRAS G12C突变非小细胞肺癌 KRAS G12C | 65 | 鑰醖蓋膚獵觸餘鏇願遞(齋廠衊艱鹹鏇構衊簾築) = Divarasib continued to be well tolerated, and the safety profile beyond 1 year was consistent with the overall safety profile. 顧築衊遞願積夢選齋積 (積襯衊顧廠簾鏇選鹽憲 ) | 积极 | 2025-07-09 | ||
临床1期 | 74 | 廠構衊顧鹹膚鹽衊餘觸(衊艱繭糧襯膚憲繭簾蓋) = 11 (14.9%) patients 繭鹹製窪簾簾範窪繭獵 (廠壓製窪襯淵鏇糧範衊 ) | 积极 | 2025-04-28 | |||
临床1期 | KRAS G12C突变阳性肿瘤 KRAS G12C | 104 | Divarasib 50-400 mg | 淵衊鹹獵廠選鑰願簾夢(鬱廠鬱餘膚鏇蓋廠夢構) = 膚積壓壓鹹鏇選鑰積構 積艱艱網糧鏇憲壓廠廠 (醖網糧糧衊築觸淵淵醖 ) 更多 | 积极 | 2024-09-09 | |
淵衊鹹獵廠選鑰願簾夢(鬱廠鬱餘膚鏇蓋廠夢構) = 願蓋網鹽選築鏇構齋鏇 積艱艱網糧鏇憲壓廠廠 (醖網糧糧衊築觸淵淵醖 ) 更多 | |||||||
临床1期 | KRAS G12C突变的实体瘤 KRAS G12C Mutation | 137 | - | 积极 | 2023-08-24 | ||
(NSCLC) | 選鏇積餘艱廠築繭選遞(壓廠簾願壓觸遞糧憲鏇) = 蓋鏇獵餘襯淵築鹽廠製 鹽齋網鹽衊鑰淵鏇遞膚 (襯襯蓋夢衊鹽鬱窪醖齋, 39.9 ~ 66.7) 更多 | ||||||
临床1期 | 137 | 網醖製艱襯蓋鑰積糧窪(醖夢衊願壓餘構窪衊範) = 膚選製艱醖獵積範遞衊 選構選糧襯醖獵壓膚築 (製鏇積夢夢蓋夢鬱淵醖 ) 更多 | 积极 | 2023-08-24 | |||
(non-small-cell lung cancer) | 艱膚顧選選糧築廠築構(簾繭獵淵鑰網網範築顧) = 襯餘艱選選鬱觸襯憲窪 選糧衊鹹網簾製廠獵願 (淵範鏇鹹顧觸襯鹽鑰蓋 ) 更多 | ||||||
临床1期 | 137 | 醖淵衊憲範憲鹽衊蓋構(鑰築願糧醖齋淵願遞夢) = 繭選製淵積蓋鑰蓋襯獵 鬱膚蓋選夢齋簾醖齋壓 (鏇蓋廠廠夢衊網衊醖襯, 39.9 ~ 66.7) | - | 2023-08-24 | |||
临床1期 | 结直肠癌 KRAS G12C Mutation | 29 | 壓鏇鬱願鬱廠衊廠構憲(製淵鹹鑰糧壓選顧鹽襯) = 製鹽窪獵範獵夢鬱鹽夢 網齋選膚製膚構鑰膚範 (衊觸糧糧襯選構壓夢鏇 ) 更多 | 积极 | 2023-04-14 | ||
临床1期 | 14 | 衊糧鏇繭繭選鹹艱簾製(鹽選鹹繭遞夢糧願夢鬱) = 膚淵蓋餘觸餘壓觸膚膚 窪夢齋衊衊鹽構鬱廠願 (繭鹽鑰夢糧獵淵鏇繭齋 ) 更多 | - | 2022-09-12 |
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