IBI351 + pemetrexed + cisplatin + carboplatin

This combination therapy consists of four drugs: **IBI351 (fulzerasib, GFH925)**, **pemetrexed**, **cisplatin**, and **carboplatin**. - **IBI351** is a potent, highly selective, irreversible covalent inhibitor of KRAS G12C mutant protein. It acts by targeting the mutant cysteine residue of KRAS G12C, binding covalently and irreversibly, which inhibits the activation of the KRAS-driven signaling pathway, resulting in tumor cell apoptosis and cell cycle arrest. IBI351 is in clinical development for solid tumors, notably non-small cell lung cancer (NSCLC) and colorectal cancer, harboring KRAS G12C mutations[1][2][3][4]. - **Pemetrexed** is a multi-targeted antifolate antineoplastic (chemotherapy) agent that inhibits several folate-dependent enzymes involved in the synthesis of thymidine and purine nucleotides, ultimately inhibiting DNA and RNA synthesis, and is routinely used in NSCLC. - **Cisplatin** and **carboplatin** are platinum-based chemotherapy agents that form DNA crosslinks, leading to inhibition of DNA replication and transcription, cell cycle arrest, and cell death. Both are commonly used in the treatment of various solid tumors including lung cancer. This combination is being studied for enhanced antitumor activity, likely in NSCLC with KRAS G12C mutations, aiming to leverage the targeted action of IBI351 in conjunction with platinum-based doublet chemotherapy and the antifolate effects of pemetrexed.