Investigational Drug
ADI PEG20
TrialFetch AI Analysis
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Overview
ADI-PEG20 (pegargiminase) is an investigational, arginine-depleting cancer treatment. Its most substantial published results are from a randomized trial in nonepithelioid pleural mesothelioma. It has also been tested in other cancers, with mixed results. (pmc.ncbi.nlm.nih.gov)
Mechanism of action
Pegargiminase is a PEGylated enzyme that converts circulating arginine into citrulline and ammonia. This may deprive tumors lacking argininosuccinate synthetase 1 (ASS1) of an amino acid they need to survive. ASS1 deficiency is therefore a potential marker of sensitivity, not a guarantee of response. (pmc.ncbi.nlm.nih.gov)
Efficacy
In the 249-patient ATOMIC-Meso trial, adding pegargiminase to first-line pemetrexed and platinum chemotherapy improved median overall survival to 9.3 months, versus 7.7 months with chemotherapy and placebo. Median progression-free survival was 6.2 versus 5.6 months. Tumor response was assessed in the phase 2 portion only; reported response rates were similar between arms. These results establish a benefit against the trial’s chemotherapy comparator, not against other treatment regimens. (pmc.ncbi.nlm.nih.gov)
Results have not been uniformly positive across cancers: in a separate phase 3 trial in advanced hepatocellular carcinoma, pegargiminase did not improve median overall survival versus placebo (7.8 versus 7.4 months). (annalsofoncology.org)
Safety
In ATOMIC-Meso, grade 3 or higher adverse events considered related to pegargiminase or placebo occurred in 28.8% of the pegargiminase-plus-chemotherapy group versus 16.9% of the placebo-plus-chemotherapy group. Pegargiminase was associated with more neutropenia; anaphylactic reactions occurred in 2.4% of its group. (pmc.ncbi.nlm.nih.gov)
Further reading
- ATOMIC-Meso randomized trial, JAMA Oncology (pmc.ncbi.nlm.nih.gov)
- Hepatocellular carcinoma phase 3 trial, Annals of Oncology (annalsofoncology.org)
Last updated: Sep 2026
Active trials using ADI PEG20
Found 2 active trials using this drug:
TrialFetch AI summary: Eligible patients are men with progressive metastatic prostate cancer meeting aggressive-variant criteria, ECOG 0–2, and limited prior chemotherapy; prior platinum or cabazitaxel for castration-resistant disease is excluded. They receive carboplatin and cabazitaxel with investigational ADI-PEG20 (pegargiminase), an arginine-depleting enzyme intended to target arginine-dependent tumors, followed by maintenance as specified in the study arm.
ClinicalTrials.gov ID: NCT06085729
TrialFetch AI summary: Adults with measurable, advanced or metastatic grade 2–3 uterine or non-uterine leiomyosarcoma previously treated with a doxorubicin-containing regimen receive gemcitabine and docetaxel plus either ADI-PEG 20 or placebo. ADI-PEG 20 (pegargiminase) depletes circulating arginine, potentially targeting ASS1-deficient tumors.
ClinicalTrials.gov ID: NCT05712694
