Bayer Begins Phase I Clinical Trial for SOS1 Inhibitor in KRAS-Mutated Tumors

Bayer has begun a phase I clinical trial for BAY3498264, an investigative oral selective inhibitor targeting Son of Sevenless Homologue 1 (SOS1). The open-label, first-in-human study (NCT06659341) will assess the safety, tolerability, and initial effectiveness of BAY3498264 in combination therapies for patients with advanced solid tumors, specifically those with KRAS G12C mutations. KRAS is one of the most frequently mutated oncogenes in human cancers, present in up to 85% of RAS-driven cancers.

BAY3498264, developed within Bayer, is designed to meet the unfulfilled medical needs of enhancing treatment outcomes targeting the mitogen-activated protein kinase (MAPK) pathway, crucial for regulating cell growth and a key factor in tumor development and cancer progression.

“Initiating this trial with our cutting-edge SOS1 small molecule inhibitor marks a pivotal advancement in our dedication to addressing primary contributors to tumor cell survival and proliferation,” stated Dominik Ruettinger, M.D., Ph.D., Bayer’s global lead for oncology research and early development at the Pharmaceuticals Division. “Our groundbreaking strategy could potentially expand treatment options for patients by slowing or halting tumor growth. We are eager to push forward our program, broadening Bayer’s innovative oncological treatments by diversifying targetable drug categories.”

When paired with a KRAS-targeting agent, BAY3498264 emerges as a promising therapy for cancers with KRAS mutations, including non-small cell lung cancer (NSCLC), pancreatic cancer, and colorectal cancers. SOS1 plays a role in activating KRAS and impacting subsequent signaling pathways. Coinhibiting SOS1 and KRAS might slow or stop cancer cell proliferation dependent on this pathway, enhancing KRAS inhibition’s effectiveness for more profound and lasting responses across various cancers.

KRAS mutations are pivotal in driving several cancer types, such as lung cancer, particularly NSCLC. Lung cancer was the leading diagnosed cancer globally in 2022, with nearly 2.5 million new cases reported worldwide. It remains the top cause of cancer-related deaths, with the International Agency for Research on Cancer (IARC) projecting substantial increases in both incidence (55.8%) and mortality (60.3%) by 2040. KRAS mutations trigger pathways fostering tumor growth and survival, making the KRAS/MAPK pathway a crucial therapeutic target to meet the needs of patients carrying these mutations.

Bayer is dedicated to enhancing lives by pursuing innovative treatments. The company’s oncology arm encompasses various marketed products for diverse conditions and numerous compounds at different clinical development stages.