ADI-PEG 20 + pemetrexed + cisplatin

ADI-PEG 20 + pemetrexed + cisplatin is a **combination regimen** investigated primarily for the treatment of **ASS1-deficient cancers**, including **mesothelioma**, **non-squamous non-small cell lung cancer**, and **metastatic uveal melanoma**. - **ADI-PEG 20** (pegargiminase) is a pegylated arginine deiminase enzyme that depletes extracellular arginine, targeting tumor cells that lack argininosuccinate synthetase 1 (ASS1), making them vulnerable to arginine deprivation-induced cytotoxicity. - **Pemetrexed** is an antifolate chemotherapy drug that inhibits key enzymes in folate metabolism required for DNA and RNA synthesis in tumor cells. - **Cisplatin** is a DNA-damaging platinum-based chemotherapy causing DNA crosslinking and apoptosis. Preclinical and early clinical data suggest synergistic cytotoxicity from the combination, as arginine depletion potentiates the effects of pemetrexed and cisplatin by interfering with DNA synthesis and repair. Clinical trials (including the TRAP study, NCT02029690) have shown acceptable safety and disease control in selected ASS1-deficient patient populations, particularly in non-epithelioid mesothelioma subtypes[1][3][4][5].

Other names

pegargiminase + pemetrexed + cisplatin