Bayer has announced the initiation of a Phase I clinical trial for BAY3498264, an investigational oral selective Son of Sevenless Homologue 1 (SOS1) inhibitor, in patients with advanced Kirsten rat sarcoma (KRAS) G12C-mutated solid tumors. This first-in-human study aims to evaluate the safety, tolerability, and preliminary efficacy of BAY3498264, potentially marking a significant advancement in the treatment of various KRAS-mutated cancers.
Targeting KRAS-Mutated Cancers
KRAS mutations are common oncogenic drivers found in up to 85% of cancers driven by RAS alterations. These mutations activate pathways that promote tumor growth and survival, making the KRAS/MAPK pathway a key therapeutic target. BAY3498264 is designed to inhibit SOS1, a protein that facilitates KRAS activation, thereby disrupting the MAPK signaling pathway crucial for cell proliferation and tumor growth. The trial will explore the potential of BAY3498264 in treating cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancer.
Study Design and Objectives
The open-label, dose-escalation study (NCT06659341) will assess BAY3498264 as a combination therapy. The primary objectives include evaluating the safety and tolerability of the drug, with preliminary efficacy as a secondary endpoint. By combining BAY3498264 with a KRAS targeting agent, the approach aims to enhance the effectiveness of KRAS inhibition, potentially leading to deeper and longer-lasting treatment responses.
Expert Commentary
Dominik Ruettinger, M.D., Ph.D., Global Head of Research and Early Development for Oncology at Bayer’s Pharmaceuticals Division, stated, “The start of the trial with our novel SOS1 small molecule inhibitor marks a significant step in our commitment to targeting key drivers of tumour cell survival and growth. This innovative approach has the potential to enhance the treatment options available for patients, offering the possibility to reduce or potentially stop tumour progression.”
Significance and Future Implications
Lung cancer, particularly NSCLC, remains a leading cause of cancer-related deaths worldwide. The International Agency for Research on Cancer (IARC) predicts significant increases in lung cancer incidence and mortality by 2040. The development of new therapies targeting KRAS mutations is therefore of critical importance. Bayer’s initiative with BAY3498264 reflects a broader effort to address the high unmet medical need in oncology, potentially paving the way for improved outcomes in patients with KRAS-mutated cancers.
