Calderasib(Calderasib) - 药物靶点：KRAS G12C_在研适应症：局部晚期非小细胞肺癌，KRAS G12C突变非鳞状非小细胞肺癌，腺癌_专利_临床

概要

基本信息

药物类型

小分子化药

别名

MK 1084、MK-1084

靶点

KRAS G12C

作用方式

抑制剂

作用机制

KRAS G12C抑制剂(KRAS G12C突变抑制剂)

治疗领域

肿瘤呼吸系统疾病消化系统疾病

在研适应症

局部晚期非小细胞肺癌KRAS G12C突变非鳞状非小细胞肺癌腺癌+ [9]

非在研适应症-

原研机构

Merck Sharp & Dohme Corp.

在研机构

Merck Sharp & Dohme Corp.Merck Sharp & Dohme LLCLonza Bend, Inc.

+ [5]

非在研机构-

权益机构-

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 (中国)

登录后查看时间轴

结构/序列

分子式C32H31ClF2N6O4

InChIKeyBBIVCWWQPMOKAC-UHFFFAOYSA-N

CAS号2641216-67-1

关联

20

项与 Calderasib 相关的临床试验

NCT07554339

/ Recruiting临床3期

A Phase 3, Randomized, Double-blind, Placebo- and Active-Comparator-Controlled Study of MK-1084 Plus Durvalumab Versus Placebo Plus Durvalumab in Participants With Locally Advanced, Unresected KRAS G12C-Mutant Non-Small Cell Lung Cancer Without Disease Progression Following Definitive Platinum-Based Chemoradiotherapy (KANDLELIT-015)

Researchers are looking for new ways to treat locally advanced non-small cell lung cancer (NSCLC) that is unresected and has a gene mutation called KRAS G12C. Researchers want to learn if calderasib (MK-1084) can be given with durvalumab, an immunotherapy, to treat NSCLC after chemotherapy and radiation therapy.
The goal of this trial is to learn if participants who receive calderasib and durvalumab live longer without the cancer growing or spreading compared to participants who receive placebo and durvalumab.

开始日期2026-06-18

申办/合作机构

Merck Sharp & Dohme LLC

ChiCTR2600124257

/ Not yet recruiting临床1/2期IIT

KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

开始日期2026-05-15

申办/合作机构-

NCT07286149

/ Recruiting临床1/2期

KEYMAKER-U01 Substudy 01F: A Phase 1b/2 Umbrella Study With Rolling Arms of Investigational Agents for Previously Treated Participants With Advanced or Metastatic Nonsquamous Non-small Cell Lung Cancer (NSCLC) With KRAS G12C Mutations

Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn:
* About the safety of MK-1084 and if people tolerate it when taken with other treatments
* How many people have the cancer respond (get smaller or go away) to the treatments

开始日期2026-04-30

申办/合作机构

Merck Sharp & Dohme LLC

[+1]

100 项与 Calderasib 相关的临床结果

登录后查看更多信息

100 项与 Calderasib 相关的转化医学

登录后查看更多信息

100 项与 Calderasib 相关的专利（医药）

登录后查看更多信息

6

项与 Calderasib 相关的文献（医药）

2026-05-28·CANCER 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 ; Benny, Jame Mathew ; Boby, Jeffrey 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.

2026-04-23·JOURNAL OF MEDICINAL CHEMISTRY

From KRAS ^G12D to Pan-KRAS Inhibitors─A Journey Enabled by Synthetic Innovation and Structure-Based Drug Design

Article

作者: Schopf, Patrick ; Lacey, Brian M. ; Day, Philip J. ; O’Reilly, Marc ; Duggal, Ruchia ; Sagara, Takeshi ; Sloman, David L. ; Edelstein, Emma ; Lyons, Thomas W. ; Hoover, Andrew ; Swaminathan, Uma ; Chessari, Gianni ; Otte, Ryan D. ; Stoeck, Alexander ; Shibata, Kazuaki ; Palani, Anandan ; Ye, Yingchun ; Bennett, D. Jonathan ; Su, Dan ; Kobayakawa, Yu ; Solban, Nicolas ; Han, Yongxin ; Miller, Richard ; Ma, Xiaoshen ; Venkataraman, Sriraman ; Howard, Steven ; Henderson, Timothy J. ; Gathiaka, Symon ; Sather, Aaron ; Shikata, Yuki ; Rees, David C. ; Munsell, Erik V. ; Oshima, Tsuyoshi ; Kawamura, Shuhei ; Mizuarai, Shinji ; Mansueto, My S.

KRAS, a significant oncology target, has been challenging to develop drugs for until recent discoveries of KRAS^G12C mutant-specific covalent inhibitors, including MK-1084. This article describes efforts toward the discovery of KRAS^G12D mutant-specific inhibitors and how synthetic innovations and structure-based drug design were utilized to facilitate the discovery of pan-KRAS inhibitors.

2026-01-23·ORGANIC LETTERS

Asymmetric Synthesis of KRAS G12C Inhibitor MK-1084 via a Crystallization-Induced Diastereomer Transformation (CIDT)

Article

作者: Kwan, Eugene E. ; Johnson, Heather C. ; Kong, Jongrock ; Wen, Xin ; Xu, Jing ; Nawrat, Christopher C. ; Chen, Yonggang ; Yuan, Yongpeng ; Shang, Gao ; He, Cyndi Qixin ; Belyk, Kevin M. ; Wan, Baoqiang ; Xiao, Kai-Jiong ; Hughes, Jonathan M. E. ; Song, Zhiguo J. ; Song, Zhiyan ; Li, Hongming ; Maddess, Matthew ; Sather, Aaron C. ; Zhang, Jin ; Yin, Jingjun ; Tan, Lushi ; Liu, Guiquan ; Fan, Chao ; Lam, Yu-hong

MK-1084 is a potent KRAS G12 inhibitor characterized by a complex macrocyclic ring system incorporating two atropisomeric axes from a restricted rotation around both C-C and N-C bonds. Herein, we report an efficient synthetic approach to manufacture MK-1084 to enable clinical trials. By leveraging the in-depth understanding of the inherent properties of axial chirality, we discovered and developed a one-pot crystallization-induced diastereomer transformation (CIDT)/carbonylation process to establish the unique and challenging macrocyclic core with double axial chiral centers from a racemic advanced precursor and readily available raw materials.

153

项与 Calderasib 相关的新闻（医药）

20 小时之前

·癌度

🔬 KRAS G12C·新突破默沙东MK-1084联合K药

🔬 KRAS G12C · 新突破默沙东MK-1084联合K药 Ⅲ期临床全国招募中 📊 核心数据速览指标数据疾病控制率（DCR）95%客观缓解率（TPS≥50%）87%中位缓解持续时间27.8个月血液G12C突变丰度下降gt;90%（6周）FDA突破性疗法认定 ✅ 2026年5月 💊 治疗机制 MK-1084 = 新一代高选择性KRAS G12C共价抑制剂联合帕博利珠单抗（K药） = PD-1免疫检查点抑制剂协同逻辑： KRAS抑制剂直接压制肿瘤生长 + PD-1抑制剂解除免疫抑制、激活T细胞＝精准打击 + 免疫唤醒，弥补单药耐药漏洞 🎯 Ⅲ期确证性研究 · 全国招募试验登记号：CTR20222590 设计：随机、双盲、多中心（全球约600例）试验组：MK-1084 + 帕博利珠单抗对照组：帕博利珠单抗 + 安慰剂（非化疗对照） ✅ 主要适合：年龄≥18岁 IV期非小细胞肺癌 KRAS G12C突变 + PD-L1 TPS≥50% 既往未接受过针对晚期病变的系统性治疗 ECOG 0-1分，有可测量病灶 🏥 全国中心：上海东方医院、上海胸科医院、北京友谊医院、中山大学肿瘤防治中心、南方医科大学南方医院、浙江省肿瘤医院、武汉协和医院、福建省肿瘤医院等 💡 从“不可成药”到精准联合 KRAS G12C曾被视为不可成药靶点。第一代抑制剂单药面临疗效有限、易耐药两大瓶颈。MK-1084以更高选择性、更低剂量，联合K药直接瞄准耐药机制，早期数据交出95%疾病控制率，获FDA突破性疗法认定。 📞 了解入组详情 👇 扫码咨询癌度

突破性疗法临床3期临床1期

21 小时之前

·癌度

疾病控制率95%!默沙东新一代KRAS G12C抑制剂联合PD-1抑制剂K药,Ⅲ期临床全国招募！

点击蓝字关注我们 KRAS是肺癌里最常见的突变基因之一,其中G12C是最常见的亚型,约占非小细胞肺癌患者的一到两成。这个靶点长期被认为"不可成药"——它的蛋白结构太"光滑",小分子药物很难抓住它。2021年,全球首款KRAS G12C抑制剂获批,才打破了这个僵局。但第一代药物有两个明显短板: 单药疗效有限(尤其结直肠癌里,客观缓解率只有约两成); 容易耐药——单药用久了,肿瘤会上调PD-L1、招募抑制性免疫细胞,悄悄给自己"松绑"。这正是为什么科学家开始把KRAS G12C抑制剂和免疫治疗放到一起用。图片来自摄图网一、MK-1084联合PD-1组合来了 MK-1084(又名calderasib),是默沙东研发的新一代口服KRAS G12C共价抑制剂。相比第一代,它的选择性更高、需要的剂量更低。而它联合帕博利珠单抗(K药)的思路很清晰:一个直接压制肿瘤生长,一个解除免疫抑制、激活T细胞——KRAS抑制剂单药容易导致的耐药机制,恰好被免疫治疗补上了这个漏洞。这个组合的早期数据相当亮眼。在未经治疗、PD-L1阳性的晚期非小细胞肺癌患者中,联合方案的客观缓解率在七成以上,PD-L1高表达的患者甚至接近九成,疾病控制率达到95%;起效也很快,中位起效时间只要1个多月;PD-L1高表达组的中位缓解持续时间超过两年。血液检测也证实了这一点——治疗6周后,患者血中KRAS G12C突变的丰度下降了九成以上,从分子层面印证了药物确实精准命中了靶点。安全性方面,联合方案的严重不良反应发生率约三成,总体和已知的同类药物相当。需要提醒的是:这些数据来自样本量不算大的Ⅰ期研究,而且随着入组患者增加、随访延长,具体的百分比还在滚动更新——这是早期研究的常态,更确切的结论要等Ⅲ期数据出来。基于这些积极信号,2026年5月,FDA已授予MK-1084联合K药突破性疗法认定,用于一线治疗KRAS G12C突变、PD-L1阳性的晚期非小细胞肺癌,这是加速新药审评的重要资格。二、如果您符合条件，可以怎么选目前,Ⅲ期确证性研究(KANDLELIT-004)正在中国多中心同步招募,对比的是MK-1084联合K药 vs K药联合安慰剂(这里要澄清一下:不是对比化疗,是安慰剂对照),面向KRAS G12C突变、PD-L1高表达(TPS≥50%)的初治晚期非小细胞肺癌患者,计划全球入组约600例。可以考虑加入年龄18岁以上; 确诊Ⅳ期非小细胞肺癌；肿瘤携带KRAS G12C突变, PD-L1 TPS≥50%; 既往未接受过针对晚期病变的系统性治疗; 体能状态较好; 有可测量病灶（大于1厘米，或淋巴结短径大于1.5厘米）。暂不适合加入 ❌ 经治的患者，确诊后已经用过化疗或靶向药的患者。 ❌ 有脑转移的患者。 ❌ 活动性乙肝/丙肝感染，或已知活动性自身免疫性疾病三、写在最后从"不可成药"到如今联合免疫治疗交出95%的疾病控制率,KRAS G12C这条赛道正在快速往前走。如果您或家人是KRAS G12C突变、PD-L1阳性的初治晚期非小细胞肺癌患者,不妨了解一下这项Ⅲ期临床试验。欢迎通过下面3个方式联系我们。 👉 点击文末【阅读原文】；或关注公众号后点菜单栏“联系我们”；或微信直接扫描下图二维码；我们协助您申请适合您的临床试验！ (本文为临床试验科普信息整理,不构成医疗建议。MK-1084为在研药物,尚未获批上市。具体入组资格以研究中心医生评估为准。) 点赞收藏分享点亮小手爱心，送来温暖鼓励

2026-08-03

·Bioconjugate 药研备忘

专利动态 | 2026.06上旬ADC专利：新靶点及新靶点组合、新linker

2026年06月上旬 ADC 药物相关的专利：新型载荷 SAMJIN 公开一篇新型 NAMPT 抑制剂为载荷的 ADC 专利，靶点 HER2； 2. 默沙东公开一篇以紫杉烷类衍生物为载荷的 ADC 专利，靶点为 PSMA。新靶点 Immunome 公开三篇涉及新靶点的ADC专利，分别为 NCAM1 ADC、SEZ6L2 ADC、DDR1 ADC，载荷均为TOP1i。双靶向/双药 ADC 正大天晴公开双抗双药 ADC 专利，靶点包括 B7H3/B7H4、EGFR/cMET、CD33/CD70、CD19/CD20，载荷为 eribulin + DDDxd，探索多种靶点组合；四川科伦博泰公开双药 ADC 专利，靶点涉及 HER2、TROP2，载荷组合为 TOP1i + 其他药物，包括 PARPi、吉西他滨、MMAE、eribulin等，探索多种双载荷组合。新偶联方法/linker OBI 公开一种新型糖基偶联专利，靶点涉及TROP2、HER2、Nectin-4，载荷为exatecan，可能涉及的项目包括 OBI-901 (TROP2 ADC) 、OBI-904 (Nectin-4 ADC)； 2. 橙帆医药公开3篇涉及新型四肽连接子的 ADC 专利，靶点涉及 Nectin-4/TROP2、EGFR/MET、CLDN18.2/CDH17、FRα/MSLN 等多组双抗组合，载荷优选 exatecan； 3. TRIPARTITE 公开新型含糖连接子专利，载荷可选TOP1i、eribulin等。 ADC 的应用专利浙江特瑞思公开 CD20 ADC 药物 TRS005 的疗法专利；默沙东/第一三共公开 HER3-Dxd 与 MK-1084 联用专利； DAIICHI SANKYO 公开CDH6 ADC 药物 DS-6000a 的疗法专利。以上内容基于个人理解，详情请自行参阅专利原文。 **说明：本公众号内容基于公开信息的整理和分析，如涉及侵权请联系处理；作者水平有限，对专利或文献的解读可能存在疏漏之处，请以原文为准；欢迎个人转发分享，如需转载至公众号或其他平台，请注明出处并遵守版权规范。** 参考资料：WIPO官网、已公开资料 END 欢迎关注，与您分享偶联药物领域最新突破

抗体药物偶联物引进/卖出

100 项与 Calderasib 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

登录

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
局部晚期非小细胞肺癌	临床3期	美国	默沙东研发（中国）有限公司	2026-06-18
局部晚期非小细胞肺癌	临床3期	美国	Merck Sharp & Dohme LLC	2026-06-18
局部晚期非小细胞肺癌	临床3期	美国	Lonza Bend, Inc.	2026-06-18
局部晚期非小细胞肺癌	临床3期	日本	Merck Sharp & Dohme LLC	2026-06-18
局部晚期非小细胞肺癌	临床3期	日本	默沙东研发（中国）有限公司	2026-06-18
局部晚期非小细胞肺癌	临床3期	日本	Lonza Bend, Inc.	2026-06-18
局部晚期非小细胞肺癌	临床3期	阿根廷	Lonza Bend, Inc.	2026-06-18
局部晚期非小细胞肺癌	临床3期	阿根廷	Merck Sharp & Dohme LLC	2026-06-18
局部晚期非小细胞肺癌	临床3期	阿根廷	默沙东研发（中国）有限公司	2026-06-18
局部晚期非小细胞肺癌	临床3期	澳大利亚	Merck Sharp & Dohme LLC	2026-06-18

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT07209111 (KANDLELIT-014, ASCO2026)	临床2期	KRAS G12C突变的实体瘤 KRAS G12C	68	MK-1084 100 mg + cetuximab 500 mg/m2	積蓋積夢餘衊繭顧鑰夢(醖蓋鑰積範鑰艱觸鏇襯) = 蓋鹽艱繭醖遞繭憲築選鑰構蓋簾顧範艱顧窪鹹 (憲衊網廠憲艱衊範鹹淵, 11.4 ~ 17.0)	积极	2026-05-29
NCT05067283 (KANDLELIT-001, ASCO2025 \| NEWS) 人工标引	临床1期	KRAS G12C突变非小细胞肺癌 \| KRAS G12C突变的实体瘤 KRAS G12C	183	MK-1084 monotherapy (arms 1 and 3 + any advanced solid tumor and ≥1 prior systemic therapy)	簾糧獵鬱淵齋積糧獵憲(衊醖製範壓壓製構憲構) = 艱製糧淵淵構鏇糧艱壓選餘網獵糧廠艱夢淵憲 (選壓艱窪遞觸鑰鹹夢願 ) 更多	积极	2025-05-30
				MK-1084 + pembrolizumab (previously untreated mNSCLC and PD-L1 TPS ≥1% + arm 2)	簾糧獵鬱淵齋積糧獵憲(衊醖製範壓壓製構憲構) = 簾構鏇繭積顧鹽顧獵願選餘網獵糧廠艱夢淵憲 (選壓艱窪遞觸鑰鹹夢願 ) 更多
NCT05067283 (KANDLELIT-001, ASCO2025 \| NEWS) 人工标引	临床1期	晚期恶性实体瘤 \| KRAS G12C突变结直肠癌 KRAS G12C	153	MK-1084 monotherapy (any advanced solid tumor and ≥1 prior systemic therapy + arms 1 and 3)	積觸艱範餘憲窪餘鏇網(簾積夢蓋鏇夢構簾顧鹽) = 鹹顧構憲遞鬱蓋遞壓鑰繭願觸膚壓衊積鹹網壓 (衊積蓋齋餘積蓋獵選遞 ) 更多	积极	2025-05-30
				MK-1084 + cetuximab (advanced CRC and 1-2 prior systemic therapies + arm 5)	積觸艱範餘憲窪餘鏇網(簾積夢蓋鏇夢構簾顧鹽) = 鹹網淵顧構憲衊窪蓋憲繭願觸膚壓衊積鹹網壓 (衊積蓋齋餘積蓋獵選遞 ) 更多
NCT06345729 (MK-1084-004, ESMO2024)	临床3期	转移性非小细胞肺癌一线 KRAS G12C mutation	-	Pembrolizumab 200 mg IV Q3W plus MK-1084 100 mg	鑰鑰齋積齋夢簾顧膚膚(衊簾簾鏇醖網壓餘夢範) = 鑰簾顧構鑰艱齋廠鑰選窪鑰鏇憲選繭夢鑰鹹鏇 (簾廠膚遞遞鏇鏇遞鑰衊, 50% ~ 86)	-	2024-09-14
NCT05067283 (phase I study, ESMO_TAT2024) 人工标引	临床1期	KRAS G12C突变的实体瘤 \| KRAS G12C突变非小细胞肺癌一线 KRAS G12C	78	MK-1084	繭範範艱築積憲鑰糧積(構窪廠餘網鑰衊衊遞膚) = 範構衊獵膚製齋鹽願齋襯膚窪積鹹簾夢選蓋艱 (衊餘範顧餘衊糧齋簾鹹 ) 更多	积极	2024-02-26
				MK-1084 + pembrolizumab	繭範範艱築積憲鑰糧積(構窪廠餘網鑰衊衊遞膚) = 構製夢鹽鹽鏇願製繭製襯膚窪積鹹簾夢選蓋艱 (衊餘範顧餘衊糧齋簾鹹 ) 更多
NCT05067283 (MK-1084-001 \| 1084-001, ESMO 12023 \| ESMO 22023) 人工标引	临床1期	实体瘤 \| 非小细胞肺癌 KRAS G12C mutation	58	MK-1084	廠鏇襯窪餘廠製餘窪壓(夢壓鑰廠艱餘鹽鏇鬱齋) = 構廠鏇遞艱壓壓鏇簾鏇窪鏇膚艱築襯夢夢蓋鑰 (鹹餘壓簾夢襯壓簾簾簾 ) 更多	积极	2023-10-23
				MK-1084 + pembrolizumab	廠鏇襯窪餘廠製餘窪壓(夢壓鑰廠艱餘鹽鏇鬱齋) = 壓壓願膚餘選網獵蓋構窪鏇膚艱築襯夢夢蓋鑰 (鹹餘壓簾夢襯壓簾簾簾 ) 更多