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This combination therapy is being evaluated in the Phase II ONTOP clinical trial for the treatment of advanced microsatellite stable (MSS) or proficient mismatch repair (pMMR) colorectal cancer. The regimen consists of **ongericimab** (JS002), a monoclonal antibody targeting PCSK9; **toripalimab** (JS001), a monoclonal antibody targeting the PD-1 receptor; **bevacizumab**, an anti-VEGF monoclonal antibody; and the **FOLFOX** chemotherapy regimen (oxaliplatin, calcium folinate, and 5-fluorouracil). The study, sponsored by Shanghai Pudong Hospital, investigates whether the addition of a PCSK9 inhibitor can overcome the typical resistance of MSS/pMMR colorectal tumors to immune checkpoint inhibitors by modulating the tumor microenvironment and enhancing MHC-I expression.
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