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Pegargiminase + temozolomide is an investigational combination therapy developed by Polaris Group for the treatment of glioblastoma multiforme (GBM) and other high-grade gliomas. The regimen combines pegargiminase (ADI-PEG 20), a PEGylated recombinant bacterial enzyme (arginine deiminase), with the standard-of-care alkylating agent temozolomide. Pegargiminase functions by depleting extracellular arginine, thereby starving tumor cells that are auxotrophic for arginine due to a deficiency in argininosuccinate synthetase 1 (ASS1). Temozolomide complements this metabolic targeting by inducing DNA damage through alkylation. This combination is currently being evaluated in Phase 1/2 clinical trials, including the GBM AGILE adaptive platform trial, to exploit the metabolic vulnerability of ASS1-deficient brain tumors.
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