olomorasib + pemetrexed + cisplatin

Olomorasib + pemetrexed + cisplatin is an investigational combination therapy studied for the first-line treatment of advanced KRAS G12C-mutant non-small cell lung cancer (NSCLC). **Olomorasib** (LY3537982) is an oral, small molecule inhibitor targeting KRAS G12C, a mutant form of the KRAS oncogene frequently found in NSCLC. **Pemetrexed** is an antimetabolite chemotherapy agent that inhibits folate-dependent enzymes essential for DNA and RNA synthesis. **Cisplatin** is a platinum-based chemotherapy drug that forms DNA crosslinks, leading to apoptosis. This combination is being studied in phase 3 clinical trials as part of a regimen with immunotherapy (commonly pembrolizumab), aiming to increase progression-free survival and response rates beyond what is achieved with standard chemotherapy or immunotherapy alone. The combination is not FDA approved as of 2025; olomorasib plus pembrolizumab received FDA breakthrough designation for this NSCLC population, but the triple combination is still under investigation[1][3][5].