Ph 2/3 Study in Subjects With MPM to Assess ADI-PEG 20 With Pemetrexed and Cisplatin

Summary

This is a study of ADI-PEG 20 (pegylated arginine deiminase), an arginine degrading enzyme versus placebo in patients with malignant pleural mesothelioma. Malignant pleural mesothelioma have been found to require arginine, an amino acid. Thus the hypothesis is that by restricting arginine with ADI-PEG 20, the malignant pleural mesothelioma cells will starve and die.

Timeline

Start

2017-08-01

Primary completion

2022-08-15

Completion

2022-08-15

Outcome

Sources disagree · no verdict is set; each source's reading is shown below

registry analysis (superiority test); Drug: ADI-PEG 20 Plus Pem Platinum vs Drug: Placebo Plus Pem Platinum; p = 0.9489 reads as mixed primary results NCT02709512 ↗

registry p = 0.0078; Cox Proportional Hazard 0.64 (95% CI 0.47 to 0.88); Log Rank reads as mixed primary results NCT02709512 ↗

registry p = 0.0234; Cox Proportional Hazard 0.71 (95% CI 0.55 to 0.93); Log Rank reads as mixed primary results NCT02709512 ↗

release “此次發表的數據為一項多國、多中心、隨機、雙盲、對照安慰劑的臨床2/3期研究，評估ADI-PEG 20與Pemetrexed和Cisplatin聯合使用治療不可切除的惡性肺間皮癌（MPM）的療效。研究顯示，隨機分配至ADI-PEG 20與Pemetrexed和Cisplatin聯合使用的患者中，中位數總生存期為9.3個月，而對照組為7.66個月，兩組差異在總生存期之療效終點上達到統計顯著意義（p value=0.0234）。” reads as met primary endpoint polarispharma.com ↗

Publications

• Szlosarek PW, Creelan BC, Sarkodie T, Nolan L, Taylor P, Olevsky O, Grosso F, Cortinovis D, Chitnis M, Roy A, Gilligan D, Kindler H, Papadatos-Pastos D, Ceresoli GL, Mansfield AS, Tsao A, O'Byrne KJ, Nowak AK, Steele J, Sheaff M, Shiu CF, Kuo CL, Johnston A, Bomalaski J, Zauderer MG, Fennell DA; ATOMIC-Meso Study Group. Pegargiminase Plus First-Line Chemotherapy in Patients With Nonepithelioid Pleural Mesothelioma: The ATOMIC-Meso Randomized Clinical Trial. JAMA Oncol. 2024 Apr 1;10(4):475-483. doi: 10.1001/jamaoncol.2023.6789.
• Szlosarek PW, Phillips MM, Pavlyk I, Steele J, Shamash J, Spicer J, Kumar S, Pacey S, Feng X, Johnston A, Bomalaski J, Moir G, Lau K, Ellis S, Sheaff M. Expansion Phase 1 Study of Pegargiminase Plus Pemetrexed and Cisplatin in Patients With Argininosuccinate Synthetase 1-Deficient Mesothelioma: Safety, Efficacy, and Resistance Mechanisms. JTO Clin Res Rep. 2020 Sep 3;1(4):100093. doi: 10.1016/j.jtocrr.2020.100093. eCollection 2020 Nov.
• Uprety D. CheckMate 743: A Glimmer of Hope for Malignant Pleural Mesothelioma. Clin Lung Cancer. 2021 Mar;22(2):71-73. doi: 10.1016/j.cllc.2020.11.009. Epub 2020 Dec 2. No abstract available.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Pegargiminase	Protein / enzyme biologic	36 mg/m2	Intramuscular
Background	Carboplatin	Small molecule	5 unknown	Intravenous
Background	Cisplatin	Other / unclassified	75 mg/m2	Intravenous
Background	Pemetrexed	Small molecule	500 mg/m2	Intravenous

Indications