Bayer starts Phase I study with SOS1 inhibitor in patients with advanced KRAS-mutated tumours

• BAY3498264 is an investigational oral selective SOS1 inhibitor with potential to treat a variety of KRAS-mutated cancers, such as non-small cell lung cancer, pancreatic cancer and colorectal cancer
• KRAS is one of the most commonly mutated oncogenes in human cancer, found in up to 85% of cancers driven by RAS alterations¹
• In-house developed compound is being evaluated for efficacy of treatment targeting the MAPK signaling pathway, which regulates cell proliferation and plays an important role in tumour growth and carcinogenesis
• Innovative clinical candidate with therapeutic potential across several tumour types, further advancing Bayer’s precision oncology development portfolio

Reading, UK, 12 December 2024 – 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 tumours.3 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.1

Developed in-house, BAY3498264 is being evaluated for the potential to address 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 tumour growth and carcinogenesis2.

“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,” 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 programme through clinical development, strengthening Bayer’s innovative oncology treatments by broadening the range of druggable targets”.

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.

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.4 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 2040.5 KRAS mutations activate pathways that promote tumour growth and survival, making the KRAS/MAPK pathway a key therapeutic target for addressing the needs of patients with these mutations.