Olomorasib

礼来公司（Eli Lilly and Company）今日宣布，美国FDA已授予其KRAS G12C抑制剂olomorasib（LY3537982）突破性疗法认定，与抗PD-1疗法Keytruda（pembrolizumab）联用，一线治疗不可切除的晚期或转移性非小细胞肺癌（NSCLC）患者。这些患者携带KRAS G12C突变且PD-L1表达水平≥50%。 KRAS是所有肿瘤类型中最常见的致癌基因之一，而KRAS G12C突变在约13%的NSCLC患者和1-3%的其他实体瘤患者中发生。Olomorasib是一款在研的口服高效且具高度选择性的第二代KRAS G12C蛋白共价抑制剂，具备超过90%靶点占有率的潜力，潜在支持更安全、毒性更低的联合治疗。 这一突破性疗法认定主要基于LOXO-RAS-20001临床1/2期试验及SUNRAY-01临床3期试验剂量优化部分的积极数据。礼来在即将举行的世界肺癌大会（WCLC）研究中，将公布LOXO-RAS-20001和SUNRAY-01试验剂量优化队列一线患者接受olomorasib联合pembrolizumab的综合分析结果。 会议摘要显示，截至2025年1月15日，共有85例患者接受olomorasib联合pembrolizumab治疗，其中14例（17%）在入组前接受过一个周期的pembrolizumab治疗。患者群体中，63%为PD-L1≥50%，21%为PD-L1 1-49%，16%为PD-L1<1%（1例未知）。 在中位随访7.6个月时，最常见的治疗相关不良事件（TRAEs，发生率≥20%）包括腹泻（29%）和肝酶ALT/AST升高（26%/25%）。≥3级TRAEs主要为ALT/AST升高（18%/14%）和腹泻（7%），总体可通过剂量调整和/或糖皮质激素进行控制。安全性方面，29%的患者因不良事件降低剂量，9%的患者停用联合治疗。 ▲Olomorasib联合pembrolizumab治疗的试验结果摘要（图片来源：参考资料[2]） 疗效方面，在所有可评估患者（n=82）中，客观缓解率（ORR）为71%，疾病控制率（DCR）为92%；在PD-L1≥50%且接受每日两次100 mg olomorasib治疗的患者中（n=26），ORR高达85%，DCR为92%。此外，该联合疗法展现出持久疗效，中位缓解持续时间（DOR）尚未达到，6个月无进展生存率达到77%。 这些最新数据进一步印证了olomorasib联合pembrolizumab在一线治疗KRAS G12C突变NSCLC患者中的潜力，并为正在进行的SUNRAY-01临床3期研究提供了有力支持。 参考资料： [1] Lilly's olomorasib receives U.S. FDA's Breakthrough Therapy designation for the treatment of certain newly diagnosed metastatic KRAS G12C-mutant lung cancers. Retrieved September 4, 2025 from https://www.prnewswire.com/news-releases/lillys-olomorasib-receives-us-fdas-breakthrough-therapy-designation-for-the-treatment-of-certain-newly-diagnosed-metastatic-kras-g12c-mutant-lung-cancers-302545643.html [2] MA02New Treatment Strategies in Other Than EGFR-Positive Tumors. Retrieved September 4, 2025 from https://cattendee.abstractsonline.com/meeting/21151/Session/212 免责声明：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：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

The Breakthrough Therapy designation for olomorasib is based on data from the Phase 1/2 LOXO-RAS-20001 trial and Phase 3 SUNRAY-01 trial Updated efficacy and safety data for olomorasib will be presented at the IASLC 2025 World Conference on Lung Cancer INDIANAPOLIS, Sept. 4, 2025 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to olomorasib, in combination with anti-PD-1 therapy KEYTRUDA (pembrolizumab), for the first-line treatment of patients with unresectable advanced or metastatic non-small cell lung cancer (NSCLC) with a KRAS G12C mutation and PD-L1 expression ≥ 50%, as determined by FDA approved tests. Olomorasib is a potent and highly selective second-generation inhibitor of KRAS G12C with preliminary evidence of central nervous system (CNS) activity. Breakthrough Therapy designation aims to expedite the development and review of drugs that are intended to treat a serious condition when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on a clinically significant endpoint(s) over already available therapies that have received full FDA approval. "The Breakthrough Therapy designation recognizes the potential for olomorasib to be a meaningful treatment advance and highlights the continued unmet need for improved options for patients with KRAS G12C-mutant NSCLC, particularly in the first-line setting in combination with standard-of-care immunotherapy," said David Hyman, M.D., Lilly chief medical officer. "We look forward to presenting updated data from the olomorasib development program in significantly more patients and with longer follow-up at WCLC and continuing to investigate olomorasib in combination with immunotherapy-based regimens in a variety of treatment settings across the Phase 3 SUNRAY-01 and SUNRAY-02 studies." The FDA Breakthrough Therapy designation is based on encouraging results from the Phase 1/2 LOXO-RAS-20001 trial and the dose optimization portion of the Phase 3 SUNRAY-01 trial. Updated results from an integrated analysis from these studies will be presented at the 2025 World Conference on Lung Cancer (WCLC) hosted by the International Association for the Study of Lung Cancer (IASLC), taking place Sept. 6 - 9 in Barcelona, Spain. Details on Presentations at the IASLC 2025 World Conference on Lung Cancer In an oral presentation (Abstract #MA02.06), Lilly will report on an integrated analysis of efficacy and safety results in patients with KRAS G12C-mutant NSCLC who received olomorasib plus pembrolizumab as first-line treatment in the dose optimization cohorts of the Phase 1/2 LOXO-RAS-20001 study and Phase 3 SUNRAY-01 study. These data will be shared in an oral presentation during the New Treatment Strategies in Other Than EGFR-Positive Tumors session on Sunday, Sept. 7, 2025, from 12-1:15 p.m. Central European Summer Time (CEST). In a second oral presentation (Abstract #OA08.02), Lilly will report results of an integrated analysis in patients with KRAS G12C-mutant advanced or metastatic NSCLC who received olomorasib in combination with chemoimmunotherapy (pembrolizumab, pemetrexed and platinum) as a first-line treatment in the Phase 1/2 LOXO-RAS-20001 trial and safety lead-in for the Phase 3 SUNRAY-01 trial. These data will be shared in an oral presentation during the Improving Outcomes in EGFR and KRAS Mutant Tumors, More is Better session on Monday, Sept. 8, 2025, from 12-1:15 p.m. CEST. The submitted abstracts for both presentations utilized a Jan. 15, 2025 data cut-off date, and the oral presentations will utilize a June 6, 2025 data cut-off date. For more information on the olomorasib Phase 3 studies SUNRAY-01 (NCT06119581) and SUNRAY-02 (NCT06890598), please visit . About LOXO-RAS-20001 LOXO-RAS-20001 is an open-label, multicenter, Phase 1/2 study evaluating the safety, tolerability and preliminary efficacy of olomorasib in patients with KRAS G12C-mutant advanced solid tumors (NCT04956640). The study includes a Phase 1a dose escalation phase of olomorasib monotherapy in KRAS G12C-mutant solid tumors and a Phase 1b dose expansion and optimization phase which are evaluating olomorasib as a monotherapy and in combination with other treatments. About SUNRAY-01 SUNRAY-01 is a randomized, double-blind, placebo-controlled, global Phase 3 study evaluating the efficacy and safety of olomorasib in combination with pembrolizumab with or without chemotherapy as a first-line treatment for patients with KRAS G12C-mutant metastatic non-small cell lung cancer (NSCLC). The trial is designed to compare olomorasib plus standard-of-care therapies versus placebo plus standard-of-care therapies, with the goal of determining whether the addition of olomorasib can improve clinical outcomes in this patient population. SUNRAY-01 is part of Lilly's broader clinical development program investigating olomorasib across multiple stages and settings of KRAS G12C-mutant NSCLC (NCT06890598). About Olomorasib Olomorasib (LY3537982) is an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein. KRAS is the most common oncogene across all tumor types, and KRAS G12C mutations occur in 13% of patients with non-small cell lung cancer (NSCLC), and 1-3% of patients with other solid tumors.1 Olomorasib is a highly potent covalent inhibitor with potential for greater than 90% target occupancy, which may allow for safer combinations with less toxicity.2 Olomorasib is currently being studied in KRAS G12C-mutated cancers in combination with pembrolizumab with or without chemotherapy for first-line treatment of advanced NSCLC, in combination with immunotherapy for the treatment of resected and unresectable NSCLC, and as monotherapy and in combinations in other advanced solid tumors, including: NCT06119581, NCT06890598, and NCT04956640. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help tens of millions of people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram, and LinkedIn. P-LLY Trademarks and Trade Names All trademarks or trade names referred to in this press release are the property of the company, or, to the extent trademarks or trade names belonging to other companies are references in this press release, the property of their respective owners. Solely for convenience, the trademarks and trade names in this press release are referred to without the ® and ™ symbols, but such references should not be construed as any indicator that the company or, to the extent applicable, their respective owners will not assert, to the fullest extent under applicable law, the company's or their rights thereto. We do not intend the use or display of other companies' trademarks and trade names to imply a relationship with, or endorsement or sponsorship of us by, any other companies. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about olomorasib as a potential treatment for people with certain KRAS G12C-mutant advanced solid tumors, preclinical data for an antibody-drug conjugate targeting folate receptor alpha and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there is no guarantee that planned or ongoing studies will be completed as planned, that future study results will be consistent with study results to date, that any of these therapies will prove to be a safe and effective treatment or receive regulatory approval, or that Lilly will execute its strategy as expected. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release. References : Ji, Wang C, Fakih M. Targeting KRASG12C-mutated advanced colorectal cancer: Research and clinical developments. OncoTargets and Therapy. 2022;Volume 15:747-756. doi:10.2147/ott.s340392 Peng S-B, Si C, Zhang Y, et al. Abstract 1259: Preclinical characterization of Ly3537982, a novel, highly selective and potent KRAS-G12C inhibitor. Cancer Research. 2021;81(13_Supplement):1259-1259. doi:10.1158/1538-7445.am2021-1259 SOURCE Eli Lilly and Company WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED