pegargiminase + pemetrexed + cisplatin

Pegargiminase + pemetrexed + cisplatin (ADIPemCis) is a combination oncology regimen developed by Polaris Group. The regimen combines pegargiminase (ADI-PEG 20), a PEGylated recombinant arginine deiminase biologic, with the standard-of-care chemotherapies pemetrexed and cisplatin. Pegargiminase works by depleting extracellular arginine, which selectively targets tumors deficient in argininosuccinate synthetase 1 (ASS1) — an enzyme required for the de novo synthesis of arginine. This metabolic deprivation induces cell death in ASS1-deficient cancer cells, which are auxotrophic for arginine. Pemetrexed and cisplatin provide complementary cytotoxic activity by inhibiting DNA synthesis and inducing DNA damage, respectively. The combination is primarily being developed for non-epithelioid malignant pleural mesothelioma (MPM), where it has shown a significant overall survival benefit in the Phase 2/3 ATOMIC-MESO trial. It is also being investigated in other ASS1-deficient cancers, such as non-small cell lung cancer and uveal melanoma.

Other names

ADI-PEG 20 + pemetrexed + cisplatin