Last updated: July 1, 2026 — refreshed post-ASCO 2026 (June 5–9, Chicago)
ASCO 2026 (June 5–9, Chicago) did not feature new headline ADI-PEG 20 readouts — the program was not among the seven drugs highlighted in the ASCO 2026 wrap-up. The two pivotal Phase 3 oncology trials remain ongoing and recruiting: the ARGSARC Phase 3 in previously-treated leiomyosarcoma (NCT05712694, ADI-PEG 20 + gemcitabine + docetaxel) and the biomarker-enriched high-arginine HCC Phase 3 (NCT05317819, vs placebo in unresectable hepatocellular carcinoma with elevated serum arginine). The earlier ATOMIC-Meso Phase 3 in first-line pleural mesothelioma reported positive overall-survival data in 2024 and is no longer enrolling; regulatory filings are anticipated. A new pediatric/AYA Phase 1/2 trial of ADI-PEG 20 + radiotherapy + temozolomide in newly-diagnosed high-grade glioma (NCT07389278) is not-yet-recruiting and listed in the "Coming Soon" subsection below. See our ASCO 2026 wrap-up for the year's broader patient takeaways across other drug classes.
ADI-PEG 20 (international nonproprietary name pegargiminase) is a recombinant PEGylated arginine deiminase developed by Polaris Pharmaceuticals. Arginine deiminase is a bacterial enzyme that converts the amino acid arginine into citrulline; PEGylation extends its circulating half-life from minutes to days, enabling once-weekly intramuscular dosing.
Mechanism of action:ADI-PEG 20 depletes circulating arginine. Most normal cells can resynthesize arginine through the urea cycle using the enzymes argininosuccinate synthetase 1 (ASS1) and argininosuccinate lyase (ASL). Many tumors lose ASS1 expression and become arginine auxotrophs — they cannot make their own arginine and rely on dietary/circulating supply. Depleting serum arginine selectively starves these tumors while sparing most normal tissues.
Regulatory status:Not yet FDA-approved. The Phase 3 ATOMIC-Meso trial in first-line malignant pleural mesothelioma reported positive overall survival data in 2024 (ADI-PEG 20 + cisplatin/pemetrexed vs cisplatin/pemetrexed alone); regulatory filings are anticipated. Additional Phase 3 trials in hepatocellular carcinoma and leiomyosarcoma are currently recruiting.
The largest current oncology focus. Two trials with distinct strategies — biomarker-enriched monotherapy and combination-with-TKI:
Leiomyosarcoma is a known arginine-auxotroph tumor type. The ARGSARC Phase 3 evaluates ADI-PEG 20 in the post-anthracycline setting:
Aggressive variant prostate cancer (AVPC) is a lineage-plastic subset of mCRPC, often after AR-pathway failure, with frequent ASS1-deficiency:
Glioblastoma is increasingly recognized as arginine-dependent; ADI-PEG 20 is integrated as one arm within the international GBM AGILE adaptive platform:
Arginine depletion as a metabolic intervention in non-alcoholic steatohepatitis — a distinct development pathway, included here for completeness:
A new pediatric / adolescent / young-adult study posted to ClinicalTrials.gov but not yet open to enrollment as of this refresh:
Showing all 6 recruiting interventional trials + 1 not-yet-recruiting. View the latest on ClinicalTrials.gov.
The clinical premise behind ADI-PEG 20 is that some tumors have lost the ability to make their own arginine and depend on circulating supply. The two most-studied molecular indicators are:
Most trials do not require pre-confirmed ASS1 status for enrollment, but discussing tissue testing with your oncologist can help inform trial choice.
What is ADI-PEG 20?
ADI-PEG 20 (pegargiminase) is PEGylated arginine deiminase — a recombinant bacterial enzyme that depletes circulating arginine. Developed by Polaris Pharmaceuticals, it exploits the fact that many tumors are arginine auxotrophs (typically because they have lost the ASS1 enzyme) and cannot make their own arginine. Not yet FDA-approved; multiple Phase 3 trials are ongoing.
Which cancers does ADI-PEG 20 target?
The most clinically advanced indications are pleural mesothelioma (Phase 3 ATOMIC-Meso reported positive first-line data in 2024), hepatocellular carcinoma (HCC), leiomyosarcoma, aggressive variant prostate cancer, and selected gliomas. ASS1-deficiency by immunohistochemistry is the typical underlying biomarker. The HCC Phase 3 uses a high-serum-arginine eligibility threshold as an additional enrichment criterion.
What ADI-PEG 20 trials are currently recruiting?
There are 6 recruiting interventional ADI-PEG 20 trials as of July 2026 (post-ASCO 2026). The two Phase 3 oncology trials are in high-arginine unresectable HCC (vs placebo, NCT05317819) and in previously-treated leiomyosarcoma (ARGSARC: ADI-PEG 20 + gem/doc, NCT05712694). Phase 2 trials include ADI-PEG 20 + lenvatinib in HCC (NCT06034977) and ADI-PEG 20 + carboplatin + cabazitaxel in aggressive variant prostate cancer (NCT06085729). The international GBM AGILE adaptive platform (NCT03970447) includes ADI-PEG 20 as one investigational arm, and a separate Phase 2 trial in non-alcoholic steatohepatitis (NASH, NCT05842512) is recruiting. A pediatric/AYA Phase 1/2 in newly-diagnosed high-grade glioma (NCT07389278) is not-yet-recruiting. ASCO 2026 (June 5–9, Chicago) did not feature new ADI-PEG 20 readouts — the ARGSARC and high-arginine HCC Phase 3 trials remain the headline readouts to watch.
What are the main side effects of ADI-PEG 20?
ADI-PEG 20 is generally well-tolerated relative to cytotoxic chemotherapy. The most common side effects are mild allergic-type reactions (often at the injection site), low neutrophil counts (manageable, more common in combination regimens), and fatigue. Anti-drug antibodies against the PEGylated enzyme can develop and gradually reduce arginine-depleting activity. Rare but serious hyperammonemia has been reported in patients with impaired urea-cycle function. Combination regimens add the toxicities of the partner drug.
Find ADI-PEG 20 and Arginine-Depletion Trials Matched to Your Situation
Use ClinTrialFinder's AI-powered matching to find ADI-PEG 20 and other arginine-depletion or biomarker-targeted trials based on your specific cancer type, prior treatments, and ASS1 status.
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