A PHASE I EXPANSION STUDY OF PEGARGIMINASE CISPLATIN AND PEMETREXED IN ARGININOSUCCINATE SYNTHETASE 1-NEGATIVE RECURRENT HIGH GRADE GLIOMAS (HGGS)

摘要

BACKGROUNDPatients (pts) with recurrent HGGs are usually managed with alkylating chemotherapy +/- bevacizumab. However, prognosis remains poor with an overall survival (OS) of 7–9 months. Preclinically, we showed that HGGs are a target for arginine depletion with Pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-ve HGGs, thereby impacting sensitivity to the antifolate, pemetrexed.