A Phase I Study of Pegylated Arginine Deiminase (Pegargiminase), Cisplatin, and Pemetrexed in Argininosuccinate Synthetase 1-Deficient Recurrent High-grade Glioma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Peter E HallPeter W Szlosarek

Abstract

Patients with recurrent high-grade gliomas (HGG) are usually managed with alkylating chemotherapy ± bevacizumab. However, prognosis remains very poor. Preclinically, we showed that HGGs are a target for arginine depletion with pegargiminase (ADI-PEG20) due to epimutations of argininosuccinate synthetase (ASS1) and/or argininosuccinate lyase (ASL). Moreover, ADI-PEG20 disrupts pyrimidine pools in ASS1-deficient HGGs, thereby impacting sensitivity to the antifolate, pemetrexed. We expanded a phase I trial of ADI-PEG20 with pemetrexed and cisplatin (ADIPEMCIS) to patients with ASS1-deficient recurrent HGGs (NCT02029690). Patients were enrolled (01/16-06/17) to receive weekly ADI-PEG20 36 mg/m2 intramuscularly plus pemetrexed 500 mg/m2 and cisplatin 75 mg/m2 intravenously once every 3 weeks for up to 6 cycles. Patients with disease control were allowed ADI-PEG20 maintenance. The primary endpoints were safety, tolerability, and preliminary estimates of efficacy. Ten ASS1-deficient heavily pretreated patients were treated with ADIPEMCIS therapy. Treatment was well tolerated with the majority of adverse events being Common Terminology Criteria for Adverse Events v4.03 grade 1-2. The best overall response was stable disease in 8 patien...Continue Reading

References

May 15, 2004·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Francesco IzzoSteven A Curley
Mar 11, 2005·The New England Journal of Medicine·Roger StuppUNKNOWN National Cancer Institute of Canada Clinical Trials Group
Oct 20, 2005·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Paolo A AsciertoTheodore F Logan
Jun 22, 2006·Expert Opinion on Investigational Drugs·Lynn Feun, Niramol Savaraj
Dec 6, 2006·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Peter W SzlosarekDean A Fennell
Dec 23, 2008·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·E A EisenhauerJ Verweij
Jul 28, 2009·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Alessandra BearzUmberto Tirelli
Jan 28, 2010·International Journal of Cancer. Journal International Du Cancer·Barbara DelagePeter W Szlosarek
Feb 4, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Wolfgang WickHoward A Fine
Mar 17, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Patrick Y WenSusan M Chang
Sep 22, 2010·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Michael BradaSiow-Ming Lee
Apr 4, 2013·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Hsuan-Ying HuangChien-Feng Li
Aug 14, 2013·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Tracy T BatchelorMartin van den Bent
May 16, 2014·Cancer Discovery·Jean M Mulcahy LevyAndrew Thorburn
Sep 23, 2014·JAMA Neurology·Alissa A ThomasAntonio M Omuro
Feb 3, 2016·Critical Reviews in Oncology/hematology·Katharina SeystahlMichael Weller
Apr 8, 2017·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Emma BeddowesPeter W Szlosarek
Jul 29, 2017·Nature Reviews. Cancer·Jean M Mulcahy LevyAndrew Thorburn
Nov 16, 2017·The New England Journal of Medicine·Wolfgang WickMartin J van den Bent
Apr 5, 2018·Frontiers in Oncology·Sun-Hee KimSuhendan Ekmekcioglu
Sep 9, 2018·Nature Reviews. Cancer·Rom KeshetAyelet Erez
Dec 14, 2018·Cell Death & Disease·Justyna Magdalena PrzystalNelofer Syed

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Citations

Jun 25, 2019·Therapeutic Delivery·Catarina P Reis
Jun 18, 2020·International Journal of Molecular Sciences·Sai-Fung ChungWai-Hung Lo
Apr 25, 2021·Nature Communications·Chia-Lin ChenHsing-Jien Kung
Jun 3, 2021·International Journal of Molecular Sciences·Jaewan JeonHae Yu Kim
Jul 25, 2021·Cancers·Chia-Lin ChenHsing-Jien Kung
Sep 2, 2021·Molecular Cell·Emma HajajAyelet Erez
Sep 25, 2020·International Journal of Biological Macromolecules·Suet-Ying TamYun-Chung Leung

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