Nonepithelioid malignant pleural mesotheliomas (MPMs), which comprise approximately a third of all mesotheliomas, often lack argininosuccinate synthetase 1 (ASS1) function (thus creating a metabolic dependence on exogenous arginine) and are therefore vulnerable to interventions that reduce arginine availability. Now, data from the phase II/III ATOMIC-Meso trial demonstrate the efficacy of pegargiminase (ADI-PEG20), a modified microbial enzyme, plus chemotherapy in this setting.

A total of 249 patients with any-stage histologically proven unresectable nonepithelioid MPM were randomly allocated (1:1) to receive intramuscular pegargiminase versus placebo, both in combination with pemetrexed plus either cisplatin or carboplatin. Patients were not selected for ASS1 deficiency, owing to concerns regarding the accuracy of the available anti-ASS1 antibodies. Overall survival (OS) was the primary end point.