divarasib + pembrolizumab + cisplatin + pemetrexed

This is an experimental **four-drug combination therapy** under investigation primarily for **untreated, advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) with KRAS G12C mutations**. The regimen combines: - **Divarasib**: a selective small molecule inhibitor of KRAS G12C, targeting oncogenic signaling in cancers with this specific mutation. - **Pembrolizumab**: a monoclonal antibody and immune checkpoint inhibitor targeting PD-1, enhancing the immune response against tumor cells. - **Cisplatin**: a platinum-based chemotherapeutic agent causing DNA crosslinking and apoptosis. - **Pemetrexed**: an antifolate cytotoxic chemotherapeutic agent, inhibiting multiple enzymes involved in nucleotide synthesis. Divarasib is under development by Genentech/Roche. The combination leverages targeted therapy (KRAS G12C inhibition), immunotherapy (PD-1 inhibition), and cytotoxic chemotherapy (cisplatin and pemetrexed). This approach aims to improve clinical outcomes in KRAS G12C-mutated NSCLC patients beyond those seen with standard care. Most clinical experience is in phase Ib/II settings. This four-drug combination is not yet approved for any indication[1][3][5].