RASolute 302: a Phase 3 Multicenter, Open-label, Randomized Study of RMC-6236 Versus Investigator's Choice of Standard of Care Therapy in Patients with Previously Treated Metastatic Pancreatic Ductal Adenocarcinoma (PDAC)

The purpose of this study is to evaluate the safety and efficacy of a novel RAS(ON) inhibitor compared to standard(s) of care (SOC) treatment.

开始日期2024-10-16

申办/合作机构

Revolution Medicines, Inc.

NCT06445062 / Recruiting临床1/2期

A Platform Study of RAS(ON) Inhibitors in Patients with Gastrointestinal Solid Tumors

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with novel agents.
The first three subprotocols include the following:
Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens
Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6
Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel

开始日期2024-05-24

申办/合作机构

Revolution Medicines, Inc.

NCT06162221 / Recruiting临床1/2期

A Platform Study of RAS(ON) Inhibitor Combinations in Patients with RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with each other.
The first two subprotocols include the following:
Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC

开始日期2024-01-18

申办/合作机构

Revolution Medicines, Inc.

100 项与 RMC-6236 相关的临床结果

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100 项与 RMC-6236 相关的转化医学

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100 项与 RMC-6236 相关的专利（医药）

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项与 RMC-6236 相关的文献（医药）

2025-01-01·DRUG DISCOVERY TODAY

Breakthrough in RAS targeting with pan-RAS(ON) inhibitors RMC-7977 and RMC-6236

Article

作者: Zerdes, Ioannis ; Salgkamis, Dimitrios ; Matikas, Alexios ; Filis, Panagiotis

The multi-selective tri-complex RAS(ON) inhibitors RMC-7977 and RMC-6236 signal new avenues for RAS targeting. This systematic review aims to comprehensively present the available preclinical and early clinical data on these agents. We screened Medline, Scopus, the ESMO and ASCO conference sites and ClinicalTrials.gov for related studies and found four published preclinical studies and one clinical trial. In these reports, RMC-7977 and RMC-6236 effectively drove tumor suppression, especially in non-small cell lung cancer and pancreatic ductal adenocarcinoma, and minimal effects in healthy tissue were observed. MYC amplification was reported to be a main contributor to the development of resistance. Six trials are currently ongoing, including one randomized trial, and promising results are expected from combination with other agents, such as immune-checkpoint blockers.

2024-07-01·CURRENT OPINION IN ONCOLOGY

State-of-the-art and upcoming trends in RAS-directed therapies in gastrointestinal malignancies

Review

作者: Prenen, Hans ; Vanclooster, Pieterjan ; Seghers, Sofie

Purpose of review:

Overall, the review underscores the evolving landscape of KRAS-targeted therapy and the potential for these approaches to improve outcomes for patients with gastrointestinal malignancies. It highlights the importance of ongoing research and clinical trials in advancing precision medicine strategies for KRAS-driven cancers. This review provides a comprehensive overview of the RAS signaling pathway and its significance in gastrointestinal malignancies.

Recent findings:

The introduction of KRAS inhibitor represents a significant advancement in the treatment landscape for KRAS-mutant cancers. In this review, we discuss upcoming trends in KRAS-targeted therapy, including the development of mutant-specific direct KRAS inhibitors like MRTX1133 and pan-RAS inhibitors such as RMC-6236. It also explores indirect RAS inhibitors targeting upstream and downstream components of the RAS pathway. Additionally, the review examines other upcoming strategies like combination therapies, such as CDK4/6 and ERK MAPK inhibitors, as well as adoptive cell therapy and cancer vaccines targeting KRAS-mutant cancers.

Summary:

Targeting RAS has become an important strategy in treating gastrointestinal cancer. These findings in this review underscore the importance of a multidisciplinary approach, integrating advances in molecular profiling, targeted therapy, immunotherapy, and clinical research to optimize treatment strategies for patients with KRAS-mutant gastrointestinal malignancies.

2024-06-03·Cancer discovery

Translational and Therapeutic Evaluation of RAS-GTP Inhibition by RMC-6236 in RAS-Driven Cancers

Article

作者: Singh, Mallika ; Jiang, Lingyan ; Menard, Marie ; Smith, Jacqueline A M ; Marquez, Abby ; Aguirre, Andrew J ; Gill, Adrian L ; Evans, James W ; Arbour, Kathryn C ; Brodbeck, Jens ; Blaj, Cristina ; Rosen, Michael J ; Chen, Zhe ; Salman, Zeena ; Chang, Stephanie ; Reed, Abby ; Gustafson, W Clay ; Wang, Zhengping ; Wildes, David ; Knox, John E ; Gindin, Yevgeniy ; Wang, Zhican ; Quintana, Elsa ; Parsons, Dylan ; Koltun, Elena S ; Aronchik, Ida ; Jiang, Jingjing ; Winters, Ian P ; Lee, Bianca J ; Cregg, James ; Tomlinson, Aidan C A ; Maldonato, Benjamin J ; Wang, Yingyun ; Yano, Jason K ; Seamon, Kyle J ; Holderfield, Matthew ; Wei, Xing

Abstract:

RAS-driven cancers comprise up to 30% of human cancers. RMC-6236 is a RAS(ON) multi-selective noncovalent inhibitor of the active, GTP-bound state of both mutant and wild-type variants of canonical RAS isoforms with broad therapeutic potential for the aforementioned unmet medical need. RMC-6236 exhibited potent anticancer activity across RAS-addicted cell lines, particularly those harboring mutations at codon 12 of KRAS. Notably, oral administration of RMC-6236 was tolerated in vivo and drove profound tumor regressions across multiple tumor types in a mouse clinical trial with KRASG12X xenograft models. Translational PK/efficacy and PK/PD modeling predicted that daily doses of 100 mg and 300 mg would achieve tumor control and objective responses, respectively, in patients with RAS-driven tumors. Consistent with this, we describe here objective responses in two patients (at 300 mg daily) with advanced KRASG12X lung and pancreatic adenocarcinoma, respectively, demonstrating the initial activity of RMC-6236 in an ongoing phase I/Ib clinical trial (NCT05379985).

Significance::

The discovery of RMC-6236 enables the first-ever therapeutic evaluation of targeted and concurrent inhibition of canonical mutant and wild-type RAS-GTP in RAS-driven cancers. We demonstrate that broad-spectrum RAS-GTP inhibition is tolerable at exposures that induce profound tumor regressions in preclinical models of, and in patients with, such tumors.This article is featured in Selected Articles from This Issue, p. 897

142

项与 RMC-6236 相关的新闻（医药）

2024-12-08

·药明康德

“癌症之王”患者6个月生存率达97%的KRAS靶向小分子；100%晚期前列腺癌患者应答的创新疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 泛RAS抑制剂RMC-6236在携带RAS突变或野生型RAS的晚期实体瘤患者中展现出令人鼓舞的抗肿瘤活性和安全性，携带任意RAS突变的胰腺导管腺癌（PDAC）患者的6个月生存率达97%。 2. 在肿瘤激活T细胞接合器（TRACTr）JANX007治疗晚期或转移性去势抵抗性前列腺癌（mCRPC）患者的1a期临床试验中，100%的患者达到PSA 50（PSA水平下降≥50%）标准。 3. 在一项早期临床试验中，DFP-17729联用TS-1作为晚期胰腺癌患者三线或三线以上治疗，与对照治疗相比能够显著延长患者的中位总生存期（OS）近3个月。药明康德内容团队整理 RMC-6236：公布两项1/1b期临床试验的新数据 Revolution Medicines公司公布了其在研泛RAS抑制剂RMC-6236的最新临床结果。RMC-6236是一款口服、可靶向突变和野生型RAS在GTP结合（具活性，ON）状态下的选择性抑制剂。此次公布的1/1b期多中心、开放标签、剂量递增和剂量扩展研究RMC-6236-001旨在评估RMC-6236作为单药治疗携带RAS突变或野生型RAS晚期实体瘤患者的效果。分析显示，RMC-6236单药作为转移性PDAC患者二线疗法时显示出显著疗效，支持3期临床试验RASolute 302的持续推进，具体数据如下： ▲接受RMC-6236单药治疗PDAC患者的总生存率结果（图片来源：参考资料[2]） KRAS G12X突变患者（n=22）：中位无进展生存期（PFS）为8.8个月（95% CI：8.5个月–不可估计[NE]），中位OS仍不可估计（95% CI：NE–NE）。任意RAS突变患者（n=37）：中位PFS为8.5个月（95% CI：5.9个月–NE），中位OS仍不可估算（95% CI：8.5个月–NE）。 6个月生存率：KRAS G12X突变患者为100%，任意RAS突变患者为97%。客观缓解率（ORR）：KRAS G12X突变患者为36%，任意RAS突变患者为27%。 ▲接受RMC-6236治疗NSCLC患者的总生存期结果（图片来源：参考资料[2]） RMC-6236在经治NSCLC患者中的表现同样亮眼。截至2024年9月30日，最新数据涵盖了124名携带RAS突变的经治NSCLC患者，这些患者接受了每日一次120至300毫克的RMC-6236治疗。在此剂量范围内，RMC-6236展现良好的耐受性。在40名二线或三线NSCLC患者（这些患者既往接受过免疫疗法和铂类化疗，但未接受多西他赛）中，中位PFS为9.8个月（95% CI：6–12.3个月），中位OS为17.7个月（95% CI：13.7个月–NE），ORR为38%。 JANX007：公布1a期临床试验数据 Janux Therapeutics公司公布了在研疗法JANX007的积极中期临床数据。JANX007目前正在针对晚期或转移性去势抵抗性前列腺癌患者进行的1a期临床试验中接受评估。JANX007是一款靶向前列腺特异性膜抗原（PSMA）的肿瘤激活T细胞接合器，分别靶向PSMA和T细胞表面表达的CD3受体。它的设计让JANX007在肿瘤微环境中经过蛋白酶切割而被激活，从而在降低了其潜在毒性的同时，最大化抗肿瘤免疫反应。截至2024年11月15日的数据，共有16名患者以每周一次的给药方案接受2-9 mg的目标剂量治疗。在所有剂量组中均观察到了高比例的PSA应答率和显著的PSA水平下降：100%的患者达到PSA 50标准，63%的患者达到PSA 90，31%的患者达到PSA 99。在目标剂量≥2 mg时，PSA下降具有持久性：75%的患者在≥12周内维持PSA 50，50%的患者在≥12周内维持PSA 90。不论患者的耐药驱动基因状态或是否接受过紫杉烷类药物或其它药物治疗，均观察到了深度且持久的PSA应答。在可按RECIST评估的患者中，观察到抗肿瘤活性，50%（4/8）的患者出现确认或未确认的部分缓解。安全性方面，JANX007耐受性良好，细胞因子释放综合征（CRS）及CRS相关的不良事件主要局限于治疗第一个周期，且为1级和2级。同样，与治疗相关的不良事件（TRAEs）主要也局限于第一个周期，且为1级和2级。目前尚未达到JANX007的最大耐受剂量。 DFP-17729：公布1/2a期临床试验的新数据 Delta-Fly Pharma公司宣布，DFP-17729联用TS-1或TS-1单药作为晚期胰腺癌患者的三线后治疗的2/3期临床试验已获日本医药品医疗器械综合机构（PMDA）批准。DFP-17729是一种新型方法，旨在中和酸性的肿瘤微环境。该公司首先评估了DFP-17729作为难治性胰腺癌的治疗方法，未来将寻求把其适应症扩展到其他类型的癌症。在针对晚期胰腺癌患者的1/2期研究中，与对照治疗（TS-1或吉西他滨）相比，接受DFP-17729联用TS-1作为三线或三线以上治疗超过6周的患者的中位OS有显著延长（9.0个月对比6.1个月）。此外，在接受DFP-17729治疗的胰腺癌患者中，尿液碱化与中位OS之间存在显著相关性，可作为关键的概念验证。 MBX 2109：公布1期临床试验数据 MBX Biosciences公司宣布在The Journal of Clinical Endocrinology and Metabolism杂志上发表了其候选疗法MBX 2109的1期研究结果。MBX 2109是其基于精确内分泌肽（PEP）平台开发的甲状旁腺激素（PTH）多肽前药，能够以一周一次的给药频率，提供长效的PTH活性，旨在作为治疗甲状旁腺功能减退症（HP）的潜在长效激素替代疗法。此药物于2022年7月获得美国FDA的孤儿药资格，用于治疗HP。此次公布的结果显示，MBX 2109的前药和活性药物的半衰期均较长，分别为79-95小时和184-213小时，支持每周一次的给药频率。每周给药后，药物在体内的浓度变化相对平稳，峰谷比值根据给药剂量的不同在1.47到1.79之间。此外，观察到与剂量成正比增加的白蛋白调整后的血清钙浓度以及内源性PTH（1-84）的抑制，这与健康受试者中预期的PTH药理学效果一致。安全性方面，MBX 2109重复给药在所有测试剂量下通常耐受性良好，大多数不良反应轻微，最常见的问题是注射部位反应，没有报告与药物剂量相关的严重不良事件或死亡。 RES-010：在荷兰启动1期临床试验 Resalis Therapeutics公司宣布启动RES-010的首次人体1期研究。RES-010是一种靶向脂质生物合成、线粒体功能和脂肪组织转化的主要调节因子miR-22的反义寡核苷酸（ASO）疗法，旨在重编程代谢途径，对肥胖和脂肪肝疾病具有持久的疾病缓解治疗作用。临床前研究表明，RES-010能减少脂肪量、保持瘦体重并增强能量消耗。RES-010以减少身体各部位（包括内脏和肝脏）的脂肪为目标，有望补充和增强现有抗肥胖药物（如GLP-1受体激动剂）的疗效，支持可持续的长期体重管理。1期临床试验将在健康、超重和中度肥胖受试者中探索RES-010的安全性、耐受性、药代动力学、药效学和疗效。 SRSD107：公布1期临床试验数据 Sirius Therapeutics公司宣布，其用于预防和治疗血栓栓塞性疾病的下一代小干扰RNA（siRNA）疗法SRSD107的1期临床试验的初步数据将在第66届美国血液学会（ASH）年会上公布。SRSD107是该公司开发的新型双链siRNA，特异性靶向编码人凝血因子XI（FXI）的mRNA并抑制FXI蛋白表达，从而阻断内在凝血途径并促进抗凝/抗血栓作用。此次公布的结果显示，SRSD107具有良好的安全性和有效性，可以预防血栓形成事件，并且不会增加出血风险，有望为需要慢性抗凝剂的患者提供只需每半年一次甚至每年一次的治疗。该公司计划在未来几个月内开始2期研究。 ▲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参考资料（可上下滑动查看） [1] Revolution Medicines Provides Clinical Updates from its RAS(ON) Inhibitor Portfolio. Retrieved December 2, 2024 from https://www.globenewswire.com/news-release/2024/12/02/2989693/0/en/Revolution-Medicines-Provides-Clinical-Updates-from-its-RAS-ON-Inhibitor-Portfolio.html [2] Clinical Updates on RAS(ON) Inhibitors: Monotherapy & Combinations. Retrieved December 2, 2024 from https://ir.revmed.com/static-files/34f3d4bd-7563-44a8-8eab-ea087b56919f [3] Janux Announces Doses Selected for Phase 1b Expansion Trials Supported by Encouraging Efficacy and Safety Profile Observed in Phase 1a Dose Escalation for JANX007 in mCRPC. Retrieved December 3, 2024, from https://investors.januxrx.com/investor-media/news/news-details/2024/Janux-Announces-Doses-Selected-for-Phase-1b-Expansion-Trials-Supported-by-Encouraging-Efficacy-and-Safety-Profile-Observed-in-Phase-1a-Dose-Escalation-for-JANX007-in-mCRPC/default.aspx [4] Delta-Fly Pharma Inc.: Update for Development Status of DFP-17729. Retrieved December 3, 2024, from https://www.businesswire.com/news/home/20241204497142/en/Delta-Fly-Pharma-Inc.-Update-for-Development-Status-of-DFP-17729 [5] Sirius Therapeutics to Present Data from Its Phase 1 Clinical Trial of Factor XI siRNA, a Long-Acting Next-Generation Anticoagulant for Thromboembolic Disorders at the 66th ASH Annual Meeting and Exposition. Retrieved December 3, 2024, from https://www.businesswire.com/news/home/20241202142345/en/Sirius-Therapeutics-to-Present-Data-from-Its-Phase-1-Clinical-Trial-of-Factor-XI-siRNA-a-Long-Acting-Next-Generation-Anticoagulant-for-Thromboembolic-Disorders-at-the-66th-ASH-Annual-Meeting-and-Exposition [6] MBX Biosciences Announces MBX 2109 Phase 1 Study Results Published in The Journal of Clinical Endocrinology and Metabolism. Retrieved December 3, 2024, from https://www.globenewswire.com/news-release/2024/12/02/2989746/0/en/MBX-Biosciences-Announces-MBX-2109-Phase-1-Study-Results-Published-in-The-Journal-of-Clinical-Endocrinology-and-Metabolism.html [7] The majority of the human genome is transcribed into RNAs that do not encode for the production of proteins. These non-coding RNAs (ncRNAs) play crucial biological roles in regulating cellular processes, making them an attractive therapeutic target for drug development for a range of diseases. Retrieved December 3, 2024, from https://www.resalistherapeutics.com/science/noncoding-rna-ncrna/ [8] Resalis Therapeutics Announces Initiation of Phase 1 Clinical Trial for RES-010 in Obesity. Retrieved December 6, 2024, from https://www.businesswire.com/news/home/20241203530139/en/Resalis-Therapeutics-Announces-Initiation-of-Phase-1-Clinical-Trial-for-RES-010-in-Obesity [9] QurAlis Doses First Patient With ALS in Phase 1 Clinical Trial Evaluating QRL-101, a First-in-Class Kv7 Precision Therapy for ALS. Retrieved December 6, 2024, from https://www.prnewswire.com/news-releases/quralis-doses-first-patient-with-als-in-phase-1-clinical-trial-evaluating-qrl-101-a-first-in-class-kv7-precision-therapy-for-als-302321243.html [10] Senti Bio Announces Positive Initial Clinical Data in Phase 1 Clinical Trial of SENTI-202, a Logic Gated, Selective CD33/FLT3-Targeting CAR-NK Cell Therapy for the Treatment of Relapsed/Refractory Hematologic Malignancies Including AML. Retrieved December 2, 2024, from https://www.globenewswire.com/news-release/2024/12/02/2989665/0/en/Senti-Bio-Announces-Positive-Initial-Clinical-Data-in-Phase-1-Clinical-Trial-of-SENTI-202-a-Logic-Gated-Selective-CD33-FLT3-Targeting-CAR-NK-Cell-Therapy-for-the-Treatment-of-Relap.html [11] Sudo Biosciences Announces First Participants Dosed in Phase 1 Trial of Brain-Penetrant Allosteric TYK2 Inhibitor SUDO-550. Retrieved December 6, 2024, from https://www.businesswire.com/news/home/20241202300740/en/Sudo-Biosciences-Announces-First-Participants-Dosed-in-Phase-1-Trial-of-Brain-Penetrant-Allosteric-TYK2-Inhibitor-SUDO-550/ [12] Recursion announces first patient dosed in Phase 1/2 clinical study of REC-1245, a potential first-in-class, RBM39 degrader for Biomarker-Enriched Solid Tumors and Lymphoma. 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Retrieved December 6, 2024, from https://www.globenewswire.com/news-release/2024/12/02/2989768/0/en/OncoC4-Announces-FDA-Clearance-of-IND-Application-for-Potential-Best-in-Class-PD-1-VEGF-Bispecific-AI-081-in-Advanced-Solid-Tumors.html [18] MAPLIGHT THERAPEUTICS ANNOUNCES RESULTS FROM PHASE 1 TRIAL OF NOVEL M1/M4 MUSCARINIC AGONIST IN DEVELOPMENT FOR TREATMENT OF SCHIZOPHRENIA AND ALZHEIMER'S DISEASE PSYCHOSIS. Retrieved December 6, 2024, from https://www.prnewswire.com/news-releases/maplight-therapeutics-announces-results-from-phase-1-trial-of-novel-m1m4-muscarinic-agonist-in-development-for-treatment-of-schizophrenia-and-alzheimers-disease-psychosis-302317925.html [19] Palisade Bio Announces Preliminary Data from Phase 1 Clinical Study of PALI-2108 for the Treatment of Moderate-to-Severe Ulcerative Colitis Appears to be Safe and Well Tolerated in Treated Subjects. Retrieved December 6, 2024, from https://www.globenewswire.com/news-release/2024/12/03/2990602/0/en/Palisade-Bio-Announces-Preliminary-Data-from-Phase-1-Clinical-Study-of-PALI-2108-for-the-Treatment-of-Moderate-to-Severe-Ulcerative-Colitis-Appears-to-be-Safe-and-Well-Tolerated-in.html [20] Delix Therapeutics Announces Dosing of First Patient in Phase 1b Clinical Trial for DLX-001 in Major Depressive Disorder. Retrieved December 6, 2024, from https://www.delixtherapeutics.com/news/delix-therapeutics-announces-dosing-of-first-patie/ [21] Nkarta Announces IND Clearance of Investigator-Sponsored Trial in Myasthenia Gravis and Opening of Enrollment for Ntrust-2. Retrieved December 6, 2024, from https://www.globenewswire.com/news-release/2024/12/05/2992165/0/en/Nkarta-Announces-IND-Clearance-of-Investigator-Sponsored-Trial-in-Myasthenia-Gravis-and-Opening-of-Enrollment-for-Ntrust-2.html 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

临床结果免疫疗法临床3期临床2期

2024-12-05

·GlobeNewswire-Health Care

Revolution Medicines Announces Closing of Upsized Public Offering of Common Stock and Pre-Funded Warrants and Full Exercise of Underwriters' Option to Purchase Additional Shares

Underwriters’ full exercise of option brings gross proceeds to $862.5 millionREDWOOD CITY, Calif., Dec. 05, 2024 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a clinical-stage oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced the closing of its underwritten public offering of 16,576,088 shares of its common stock at a public offering price of $46.00 per share, before underwriting discounts and commissions, and, in lieu of shares of common stock, to certain investors, pre-funded warrants to purchase 2,173,917 shares of common stock at a public offering price of $45.9999, which represents the per share public offering price for the common stock less the $0.0001 per share exercise price for each pre-funded warrant. The shares of common stock issued and sold in the offering include 2,445,652 shares issued upon exercise in full by the underwriters of their option to purchase additional shares of common stock at the public offering price, less underwriting discounts and commissions. The gross proceeds from the offering, before deducting underwriting discounts and commissions and other offering expenses payable by Revolution Medicines, were $862.5 million. All shares and pre-funded warrants in the offering were offered by Revolution Medicines. J.P. Morgan, TD Cowen, Goldman Sachs & Co. LLC and Guggenheim Securities acted as joint book-running managers for the offering. UBS Investment Bank acted as lead manager. A shelf registration statement relating to these securities was filed with the U.S. Securities and Exchange Commission (SEC) on March 4, 2024, and automatically became effective upon filing. This offering was made solely by means of a prospectus. A copy of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained for free by visiting EDGAR on the SEC’s website at www.sec.gov. Alternatively, a copy of the final prospectus supplement and the accompanying prospectus relating to this offering may be obtained by contacting: J.P. Morgan Securities LLC, Attention: Broadridge Financial Solutions, 1155 Long Island Avenue, Edgewood, New York 11717, by email at prospectus-eq_fi@jpmchase.com and postsalemanualrequests@broadridge.com; TD Securities (USA) LLC, 1 Vanderbilt Avenue, New York, New York 10017, by telephone at (855) 495-9846 or by email at TD.ECM_Prospectus@tdsecurities.com; Goldman Sachs & Co. LLC, Attention: Prospectus Department, 200 West Street, New York, NY 10282, by telephone at (866) 471-2526 or by email at prospectus-ny@ny.email.gs.com; and Guggenheim Securities, LLC, Attention: Equity Syndicate Department, 330 Madison Avenue, 8th Floor, New York, New York 10017, by telephone at (212) 518-9544 or by email at GSEquityProspectusDelivery@guggenheimpartners.com. This press release shall not constitute an offer to sell or a solicitation of an offer to buy these securities, nor shall there be any sale of these securities in any state or other jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction. About Revolution Medicines, Inc. Revolution Medicines is a clinical-stage oncology company developing novel targeted therapies for RAS-addicted cancers. The company’s R&D pipeline comprises RAS(ON) inhibitors designed to suppress diverse oncogenic variants of RAS proteins. The company’s RAS(ON) inhibitors RMC-6236, a RAS(ON) multi-selective inhibitor, RMC-6291, a RAS(ON) G12C-selective inhibitor, and RMC-9805, a RAS(ON) G12D-selective inhibitor, are currently in clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-5127 (G12V), RMC-0708 (Q61H) and RMC-8839 (G13C), in addition to RAS companion inhibitors RMC-4630 and RMC-5552. Revolution Medicines Investors & Media Contacts: investors@revmed.com; media@revmed.com

临床研究

2024-12-05

·癌度

《癌度早报2024年12月5日》

一、新药快讯 1、治疗小细胞肺癌的注射用芦比替定获得上市批准芦比替定的商品名为赞必佳，被纳入优先审评审批程序的一款抗癌药，于2024年12月3日获得国家药品监督管理局上市批准，用药治疗含铂类化疗中或化疗后病情进展的转移性小细胞肺癌成人患者，打破了20多年来小细胞肺癌二线治疗的瓶颈，基于两项临床试验，芦比替定二线治疗小细胞肺癌的治疗应答率为45.5%，中位无进展生存时间达到了5.6个月，中位总生存时间为11个月。 2、呋喹替尼联合信迪利单抗获批用于治疗子宫内膜癌 2024年12月4日，多靶点抗血管内皮生长因子受体创新药物呋喹替尼，联合免疫检查点抑制剂信迪利单抗用于治疗经过系统治疗后失败，且不适合进行根治性手术治疗或根治性放疗的子宫内膜癌，基于一项临床研究，98名晚期经过治疗后病情进展的子宫内膜癌患者，使用呋喹替尼联合信迪利单抗后治疗应答率为35.6%，疾病控制率为88.5%。 3、预防胰腺癌复发的前沿疫苗ELI-002，覆盖多种KRAS突变类型美国MD安德森癌症中心胃肠道肿瘤内科Pant教授介绍了一款胰腺癌疫苗，由于大于50%的胰腺癌会出现复发，且一旦复发之后治疗方法会很有限。这位专家正在测试ELI-002疫苗，针对KRAS基因G12D和G12R突变，这两种突变位点也是胰腺癌KRAS最常见的突变，一期临床试验表明，接种该疫苗的胰腺癌患者，84%的病人被激活了免疫T细胞免疫反应，这款疫苗正在准备二期临床试验。 4、治疗肺癌和胰腺癌的新药RMC-6236，三成患者病灶缩小或消失 RMC-6235是一种RSA抑制剂，主要是针对RAS基因突变，而RAS基因突变在多种癌症都存在，最近该药的临床试验目前招募了436名患者，包括132名非小细胞肺癌和胰腺癌，304名其他类型的实体瘤患者，这些患者使用了不同剂量的RMC-6236，对于之前治疗后耐药的胰腺癌的治疗应答率为27%，生存期大于6个月的胰腺癌患者比例达到了97%，非小细胞肺癌的治疗应答率达到了38%，平均无进展生存期为9.8个月。该药的临床研究还在进行中！

优先审批疫苗临床2期上市批准临床1期

100 项与 RMC-6236 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
转移性胰腺导管腺癌	临床3期	美国	Revolution Medicines, Inc.	2024-10-16
转移性胰腺导管腺癌	临床3期	波多黎各	Revolution Medicines, Inc.	2024-10-16
转移性结直肠癌	临床2期	美国	Revolution Medicines, Inc.	2024-05-24
结直肠癌	临床1期	法国	Revolution Medicines, Inc.	2023-11-14
结直肠癌	临床1期	德国	Revolution Medicines, Inc.	2023-11-14
结直肠癌	临床1期	意大利	Revolution Medicines, Inc.	2023-11-14
结直肠癌	临床1期	荷兰	Revolution Medicines, Inc.	2023-11-14
结直肠癌	临床1期	西班牙	Revolution Medicines, Inc.	2023-11-14
KRAS G12C突变的实体瘤	临床1期	美国	Revolution Medicines, Inc.	2023-11-14
KRAS G12C突变的实体瘤	临床1期	法国	Revolution Medicines, Inc.	2023-11-14

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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


NCT06128551 (RMC-6291-101, GlobeNewswire) 人工标引	临床1期	KRAS G12C突变的实体瘤 \| 结直肠癌 RAS G12C mutant	74	RMC-6291 + RMC-6236	鏇糧繭範繭鹽網繭艱膚(鏇構鏇糧廠憲鹽蓋獵醖) = 壓餘築積衊積觸製餘蓋艱鏇鹹壓觸憲廠網觸獵 (鹽願夢艱襯夢簾憲鑰糧 ) 更多	积极	2024-12-02
				RMC-6291 + RMC-6236 (CRC)	鏇糧繭範繭鹽網繭艱膚(鏇構鏇糧廠憲鹽蓋獵醖) = 構遞遞夢夢顧淵窪範齋艱鏇鹹壓觸憲廠網觸獵 (鹽願夢艱襯夢簾憲鑰糧 ) 更多
NCT05379985 (RMC-6236-001, GlobeNewswire) 人工标引	临床1期	胰腺导管腺癌 \| 非小细胞肺癌	436	RMC-6236 monotherapy (KRAS G12X + PDAC)	糧壓鬱蓋繭獵遞鏇憲夢(顧窪簾襯觸製遞簾鏇鏇) = 選鏇窪獵獵醖蓋選鏇遞憲獵觸製餘積蓋鏇構夢 (夢製獵餘範繭淵餘製壓, 8.5 ~ NE) 更多	积极	2024-12-02
				RMC-6236 monotherapy (RAS mutation + PDAC)	糧壓鬱蓋繭獵遞鏇憲夢(顧窪簾襯觸製遞簾鏇鏇) = 鬱鏇襯憲餘壓廠憲範憲憲獵觸製餘積蓋鏇構夢 (夢製獵餘範繭淵餘製壓, 5.9 ~ NE) 更多
RMC-LUNG-101B (GlobeNewswire) 人工标引	临床1期	非小细胞肺癌一线 RAS mutant	20	RMC-6236 + Pembrolizumab	餘夢鹹顧製窪艱製餘製(鑰繭選繭顧壓繭願齋蓋) = 鏇淵壓艱鹹膚積繭顧襯鬱蓋遞齋獵觸築繭鹹艱 (遞蓋壓壓齋鹹窪廠壓鏇 )	积极	2024-12-02
NCT05379985 (RMC-6236-001, Company_Website) 人工标引	临床1期	晚期胰腺导管腺癌二线 \| 三线 \| 末线 RAS mutations \| KRAS G12X mutation	127	RMC-6236 (harboring a KRAS G12X mutation in the second-line (2L) setting)	簾齋遞簾鹹餘齋壓鹽顧(構膚觸艱衊淵簾糧窪夢) = The most common TRAEs were rash and GI-related toxicities that were primarily Grade 1 or 2 in severity. The most common reported Grade ≥3 TRAEs were rash (8%), stomatitis (3%), and diarrhea (2%). 願醖鹽膚鏇醖鏇鹹衊構 (糧鹹顧鹽艱醖觸夢鹽鑰 )	积极	2024-10-23
				RMC-6236 (harboring any RAS mutation in the 2L setting)
NCT05379985 (WCLC2024)	临床1期	肺癌 RRAS \| RRAS2	-	RMC-6236 (RRAS Q87L mutation)	積簾艱衊窪範糧鏇製衊(獵願積壓膚衊鏇蓋衊鑰) = Enhanced ERK phosphorylation was only observed in HBEC-RRASQ87L cells 構糧繭餘願襯壓鑰構壓 (蓋餘艱齋選範鏇範齋糧 )	积极	2024-09-09
				RMC-6236 (RRAS2 Q72L mutation)
NCT05379985 (NEWS) 人工标引	临床1期	胰腺导管癌 KRAS G12X	127	RMC-6236	衊餘襯觸憲淵鹽壓觸遞(鹹壓簾範齋製夢齋願糧) = 簾顧繭築築糧築膚願網醖範範憲憲網醖鏇糧繭 (獵襯窪觸鹽膚鏇窪醖鏇 ) 更多	积极	2024-07-15
NCT05379985 (ESMO2023) 人工标引	临床1期	KRAS突变非小细胞肺癌 \| KRAS突变胰腺导管腺癌 KRAS Mutation	33	RMC-6236 (KRASG12X PDAC)	齋襯衊壓窪網糧範膚網(築製選衊壓繭廠鹹壓齋) = occurring in ≥10% of patients were rash (52%), diarrhea (21%), nausea (21%), and vomiting (15%) 齋衊築齋蓋鑰鹽蓋鏇觸 (遞齋餘鬱鏇鏇淵蓋壓糧 ) 更多	积极	2023-10-22
				RMC-6236 (KRASG12X NSCLC)