Bayer announced today initiation of a Phase I clinical trial with BAY3498264, an investigational oral selective Son of Sevenless Homologue 1 (SOS1) inhibitor. The open-label, first-in-human, dose escalation study (NCT06659341) will evaluate the safety, tolerability and preliminary efficacy of BAY3498264 as a combination therapy in patients with advanced KRAS G12C-mutated solid tumors. Kirsten rat sarcoma (KRAS) is one of the most commonly mutated oncogenes in human cancer, found in up to 85% of cancers driven by RAS alterations.

拜耳今天宣布启动 BAY3498264 的 I 期临床试验，BAY3498264 是一种研究性口服选择性 Son of Sevenless Homologue 1 (SOS1) 抑制剂。这项开放标签、首次人体剂量递增研究 (NCT06659341) 将评估 BAY3498264 作为联合疗法对晚期 KRAS G12C 突变实体瘤患者的安全性、耐受性和初步疗效。Kirsten 大鼠肉瘤 (KRAS) 是人类癌症中最常见的突变 致癌基因之一 ，在由 RAS 变异驱动的癌症中发现高达 85% 的癌症。

Developed in-house, BAY3498264 addresses the unmet medical need of improving efficacy of treatment targeting the mitogen-activated protein kinase (MAPK) signaling pathway which regulates cell proliferation and plays a critical role in tumor growth and carcinogenesis.

BAY3498264 由公司内部开发，解决了尚未满足的医疗需求，即提高针对丝裂原活化蛋白激酶 (MAPK) 信号通路的治疗效果，该信号通路可调节细胞增殖并在肿瘤生长和致癌作用中发挥关键作用。

“The start of the trial with our novel SOS1 small molecule inhibitor marks a significant step in our commitment to target key drivers of tumor cell survival and growth. This innovative approach has the potential to enhance the treatment options available for patients, offering the possibility to reduce or stop tumor progression,” said Dominik Ruettinger, M.D., Ph.D., Global Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division. “We look forward to advancing the program through clinical development strengthening Bayer’s innovative oncology treatments by broadening the range of druggable targets”.

拜耳制药部门肿瘤学研究和早期开发全球主管、医学博士 Dominik Ruettinger 表示：“我们新型 SOS1 小分子抑制剂的试验启动标志着我们致力于针对肿瘤细胞存活和生长的关键驱动因素迈出了重要一步。这种创新方法有可能增强患者的治疗选择，提供减少或阻止肿瘤进展的可能性。”“我们期待通过临床开发推进该项目，通过扩大可用药物靶点的范围来加强拜耳的创新肿瘤治疗。”

BAY3498264 is a selective SOS1 inhibitor which, when combined with a KRAS targeting agent, shows potential as a therapeutic agent for KRAS-mutant cancers, such as non-small cell lung cancer (NSCLC), pancreatic cancer and colorectal cancer. SOS1 facilitates KRAS activation and influences downstream signaling pathways. Co-inhibiting SOS1 with KRAS may help to slow or inhibit the growth of cancer cells reliant on this pathway, by enhancing the effectiveness of KRAS inhibition and contributing to deeper and/or longer-lasting treatment responses in various cancers.

BAY3498264 是一种选择性 SOS1 抑制剂，与 KRAS 靶向剂结合使用时，有望成为 KRAS 突变型癌症（如非小细胞肺癌 (NSCLC)、胰腺癌和结直肠癌）的治疗剂。SOS1 促进 KRAS 激活并影响下游信号通路。同时抑制 SOS1 和 KRAS 可能有助于减缓或抑制依赖该通路的癌细胞的生长，从而增强 KRAS 抑制的有效性，并有助于在各种癌症中产生更深层和/或更持久的治疗反应。

KRAS mutations are common drivers of several types of cancer such as lung cancer, especially in NSCLC. Lung cancer was the most diagnosed cancer in 2022 worldwide, accounting for nearly 2.5 million new cases globally.2 Lung cancer remains the leading cause of cancer-related deaths, with the International Agency for Research on Cancer (IARC) predicting significant increases in both incidence (55.8%) and mortality (60.3%) by 2040.3 KRAS mutations activate pathways that promote tumor growth and survival, making the KRAS/MAPK pathway a key therapeutic target for addressing the needs of patients with these mutations.

KRAS 突变是多种癌症（例如肺癌，尤其是 NSCLC）的常见驱动因素。肺癌是 2022 年全球确诊最多的癌症，全球新增病例近 250 万例。2肺癌仍然是癌症相关死亡的主要原因，国际癌症研究机构 (IARC) 预测，到 2040 年，发病率 (55.8%) 和死亡率 (60.3%) 都将显着增加。3 KRAS突变会激活促进肿瘤生长和存活的通路，使 KRAS/MAPK 通路成为满足这些突变患者需求的关键治疗靶点。