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YL242 + pembrolizumab + 5-fluorouracil is a combination therapy being evaluated for the treatment of advanced solid tumors. YL242 is a novel, non-internalized antibody-drug conjugate (ADC) developed by MediLink Therapeutics using the proprietary TMALIN® platform. It consists of an anti-VEGF antibody conjugated to a DNA topoisomerase I inhibitor payload (C24) via a protease-cleavable tripeptide linker. This combination pairs the anti-angiogenic and cytotoxic effects of YL242 with the immune checkpoint inhibition of pembrolizumab (a PD-1 inhibitor) and the antimetabolite activity of 5-fluorouracil. The regimen is designed to provide dual anticancer activity through both anti-angiogenesis and cytotoxicity from the extracellularly released payload in the tumor microenvironment, while simultaneously enhancing the immune response. It is currently in Phase 1/2 clinical trials for indications including non-small cell lung cancer, hepatocellular carcinoma, colorectal cancer, and gastric/gastroesophageal junction cancers.
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