ASP3082 + cisplatin + pemetrexed

ASP3082 + cisplatin + pemetrexed is a combination therapy under investigation for the treatment of advanced solid tumors harboring KRAS G12D mutations. **ASP3082** is a first-in-class, small-molecule proteolysis-targeting chimera (PROTAC) that selectively binds to and induces degradation of the mutant KRAS G12D protein via recruitment of E3 ubiquitin ligase proteins, resulting in downregulation of oncogenic signaling in cancer cells. **Cisplatin** and **pemetrexed** are cytotoxic chemotherapy agents: cisplatin is a platinum-based DNA crosslinker causing apoptosis, while pemetrexed is an antifolate that inhibits several enzymes involved in nucleotide synthesis. The rationale for combining ASP3082 with cisplatin and pemetrexed leverages both targeted degradation of mutant KRAS and broad cytotoxic effects. The regimen is being evaluated in clinical trials for safety and preliminary efficacy in patients with previously treated, advanced or metastatic solid tumors with KRAS G12D mutations, including lung, pancreatic, colorectal, and other cancers[1][2][3][4][5][6][7].