Daraxonrasib

Zoldonrasib, a RAS(ON) G12D-selective inhibitor, demonstrated acceptable tolerability and encouraging initial antitumor activity in patients with previously treated KRAS G12D mutant non-small cell lung cancer REDWOOD CITY, Calif., April 27, 2025 (GLOBE NEWSWIRE) -- Revolution Medicines, Inc. (Nasdaq: RVMD), a late-stage clinical oncology company developing targeted therapies for patients with RAS-addicted cancers, today announced new clinical data for zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, as monotherapy in patients with KRAS G12D mutant non-small cell lung cancer (NSCLC). Results were highlighted in the official press program at the American Association for Cancer Research (AACR) Annual Meeting in Chicago, Illinois, and will be featured in a late-breaking oral presentation on April 27, 2025, at 5:00 p.m. Central Time. “We are pleased to share new clinical data for zoldonrasib, our innovative, oral RAS(ON) G12D-selective inhibitor, which demonstrates acceptable safety and tolerability and encouraging initial antitumor activity in patients with non-small cell lung cancer. These data reinforce the clinical potential of zoldonrasib following the initial tolerability and antitumor activity reported late last year in patients with pancreatic ductal adenocarcinoma,” said Mark A. Goldsmith, M.D., Ph.D., chief executive officer and chairman of Revolution Medicines. “Together these results support further evaluation of zoldonrasib as monotherapy and in combination as we continue efforts to advance innovative targeted medicines for patients living with these hard-to-treat cancers.” RMC-9805-001 is a multicenter, open-label, dose escalation and dose-expansion Phase 1 study designed to evaluate zoldonrasib in patients with advanced solid tumors harboring a KRAS G12D mutation. As of a December 2, 2024 data cutoff date, 90 solid tumor patients were treated with 1200 mg once daily (QD), the candidate recommended Phase 2 dose. In these patients, zoldonrasib demonstrated an acceptable safety profile, that was generally consistent with previously reported data for this compound in pancreatic cancer, and was generally well tolerated. The most common treatment-related adverse events (TRAEs) occurring in at least 10% of patients were nausea (39%), diarrhea (24%), vomiting (18%), and rash (12%). TRAEs were primarily Grade 1 or 2 in severity, with two patients (2%) experiencing Grade 3 events that resolved following dose interruption. Zoldonrasib had a favorable mean dose intensity of 98% and no dose limiting toxicities were observed. Preliminary antitumor activity was assessed in 18 efficacy-evaluable patients with NSCLC at the 1200 mg QD dose. The objective response rate (confirmed or pending confirmation) was 61% (n=11) and the disease control rate was 89% (n=16). “There is a high unmet need for new treatments within this patient population as there are currently no targeted therapies approved for any RAS G12D mutant cancer,” said Kathryn Arbour, M.D., thoracic medical oncologist at Memorial Sloan Kettering Cancer Center and principal investigator and lead author for the RMC-9805-001 presentation. “While the data are from an early, small subset of patients, it is encouraging to see this level of tolerability and antitumor activity in patients with NSCLC carrying this RAS mutation.” About Revolution Medicines, Inc.Revolution Medicines is a late-stage clinical oncology company developing novel targeted therapies for patients with 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 daraxonrasib (RMC-6236), a RAS(ON) multi-selective inhibitor; elironrasib (RMC-6291), a RAS(ON) G12C-selective inhibitor; and zoldonrasib (RMC-9805), a RAS(ON) G12D-selective inhibitor, are currently in clinical development. The company anticipates that RMC-5127, a RAS(ON) G12V-selective inhibitor, will be its next RAS(ON) inhibitor to enter clinical development. Additional development opportunities in the company’s pipeline focus on RAS(ON) mutant-selective inhibitors, including RMC-0708 (Q61H) and RMC-8839 (G13C). For more information, please visit www.revmed.com and follow us on LinkedIn. Forward Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. Any statements in this press release that are not historical facts may be considered "forward-looking statements," including without limitation statements regarding progression of clinical studies and findings from these studies, including the safety, tolerability and antitumor activity of the company’s candidates being studied and the durability of these results; dosing and enrollment in the company’s clinical trials; and the potential of zoldonrasib as a therapeutic option for pancreatic ductal adenocarcinoma or non small cell lung cancer. Forward-looking statements are typically, but not always, identified by the use of words such as "may," "will," "would," "believe," "intend," "plan," "anticipate," "estimate," "expect," and other similar terminology indicating future results. Such forward-looking statements are subject to substantial risks and uncertainties that could cause the company’s development programs, future results, performance or achievements to differ materially from those anticipated in the forward-looking statements. Such risks and uncertainties include without limitation risks and uncertainties inherent in the drug development process, including the company’s programs’ current stage of development, the process of designing and conducting preclinical and clinical trials, risks that the results of prior clinical trials may not be predictive of future clinical trials, clinical efficacy, or other future results, the regulatory approval processes, the timing of regulatory filings, the challenges associated with manufacturing drug products, the company’s ability to successfully establish, protect and defend its intellectual property, other matters that could affect the sufficiency of the company’s capital resources to fund operations, reliance on third parties for manufacturing and development efforts, changes in the competitive landscape, and the effects on the company’s business of the global events, such as international conflicts or global pandemics. For a further description of the risks and uncertainties that could cause actual results to differ from those anticipated in these forward-looking statements, as well as risks relating to the business of Revolution Medicines in general, see Revolution Medicines’ Annual Report on Form 10-K filed with the Securities and Exchange Commission (the “SEC”) on February 26, 2025, and its future periodic reports to be filed with the SEC. Except as required by law, Revolution Medicines undertakes no obligation to update any forward-looking statements to reflect new information, events or circumstances, or to reflect the occurrence of unanticipated events. Revolution Medicines Media & Investor Contact:media@revmed.com investors@revmed.com

癌度临床试验病友交流群（点击）一、新药快讯1、 新一代KRAS多靶点靶向药对肺癌疗效喜人，38%患者病灶缩小近日，在2025年欧洲肺癌大会上，新型抗癌药物Daraxonrasib（RMC-6236）治疗RAS突变型肺癌患者的1期临床试验的数据。在40名RAS G12X突变非小细胞肺癌患者中，有38%的患者肿瘤明显缩小，平均在用药1.5个月后见效，疗效持续时间达到平均15.1个月。G12X包括G12C、G12D、G12V、G12A、G12S多种基因突变位点类型，目前该药目前已进入大规模3期临床试验阶段。2、CDK抑制剂SLS009的二期临床试验结果公布抗癌新药Tambiciclib（SLS009）公布了二期临床试验结果，该药用于治疗复发/难治性急性髓系白血病患者，尤其是维奈托克耐药的患者中展现显著疗效，13名可评估疗效、预后不佳的患者使用SLS009之后平均生存时间达到8.8个月，而这类患者在过去平均生存时间大约只有2.5个月！对于携带ASXL1突变、RUNX1突变、TP53突变的患者来说，SLS009的效果显得尤为惊人。3、口服激素受体降解剂芙仕得在国内申报上市，治疗乳腺癌2025年4月8日，CDE官网显示，芙仕得在国内申报上市，用于既往接受内分泌治疗的激素受体阳性、HER2阴性局部晚期或转移性乳腺癌患者。芙仕得是一种具有脑渗透性的口服选择性雌激素受体降解剂，三期临床试验结果表明，与标准内分泌治疗相比，在携带ESR1突变的患者中，芙仕得单药治疗降低了38%的疾病进展或死亡风险，显著改善了无进展生存期。二、抗癌前沿1、抗体偶联药德达博妥单抗联合奥希替尼缓解奥希替尼耐药？2025年欧洲肺癌大会上，MD安德森癌症中心乐秀宁教授团队公布了一项研究结果，TROP2抗体偶联药德达博妥单抗联合奥希替尼治疗奥希替尼耐药肺癌患者，两个不同德达博妥单抗剂量组的治疗应答率达到了43%和36%，中位缓解时间分别为2.7个月和1.4个月，其中高剂量组的中位无进展生存时间达到了11.7个月，德达博妥单抗与奥希替尼具有明确的协同效应，而且呈现剂量依赖性优势。