^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG CLASS:

    Arginine depleter

    Related drugs:
    1m
    Study of ADI-PEG 20 or Placebo Plus Gem and Doc in Previously Treated Subjects With Leiomyosarcoma (ARGSARC) (clinicaltrials.gov)
    P3, N=218, Terminated, Polaris Group | Trial completion date: Dec 2027 --> May 2026 | Recruiting --> Terminated | Trial primary completion date: Dec 2027 --> May 2026; Lack of Efficacy, no safety concern.
    Trial completion date • Trial termination • Trial primary completion date
    |
    gemcitabine • docetaxel • Hepacid (pegargiminase)
    1m
    Pegargiminase Suppresses the Fanconi Anemia Pathway and Promotes Melphalan-Induced DNA Double-Strand Breaks in Uveal Melanoma. (PubMed, Pigment Cell Melanoma Res)
    ADI-PEG20 downregulated multiple genes of the Fanconi anemia pathway and synergized with melphalan to increase DNA double-strand breaks. Melphalan and pegargiminase is a rational new drug combination that warrants clinical testing in uveal melanoma.
    Journal
    |
    ASS1 (Argininosuccinate synthase 1)
    |
    melphalan • Hepacid (pegargiminase)
    2ms
    Arginine deprivation enhances ASS1-negative glioblastoma radiosensitivity via epigenetic silencing of DNA repair genes. (PubMed, Cell Death Dis)
    Currently, patients with GBM are treated with surgery followed by adjuvant radiotherapy and temozolomide, both of which are DNA damaging agents. Mechanistically, in both ASS1-negative patient-derived tumor cells and a patient-derived xenograft (PDX) model, ADI-PEG20 downregulated DNA repair genes, namely poly ADP-ribose polymerase 1 (PARP1) and DNA ligase 1 (LIG1), at the epigenetic level by upregulating the repressive H3K27me3 histone marker. Collectively, our findings demonstrate that arginine deprivation is an effective strategy to enhance the radiosensitivity of ASS1-negative GBM and suggest that combination therapy with PARP inhibitors should be explored.
    Journal • PARP Biomarker
    |
    ASS1 (Argininosuccinate synthase 1) • LRIG1 (Leucine Rich Repeats And Immunoglobulin Like Domains 1)
    |
    temozolomide • Hepacid (pegargiminase)
    2ms
    GCAR-7213: Trial Designed To Evaluate Multiple Regimens In Newly Diagnosed and Recurrent Glioblastoma (GBM) (2024-511452-40-00)
    P2/3, N=120, Active, not recruiting, Global Coalition For Adaptive Research Inc. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    IDH wild-type
    |
    AZD1390 • Hepacid (pegargiminase) • Vyglxia (troriluzole)
    3ms
    Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Washington University School of Medicine | Trial completion date: May 2028 --> Jul 2026
    Trial completion date
    |
    ifosfamide • Hepacid (pegargiminase) • mesna
    3ms
    ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, Washington University School of Medicine | Trial completion date: Dec 2033 --> Jul 2026 | Trial primary completion date: Dec 2028 --> Jul 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation
    |
    gemcitabine • docetaxel • Hepacid (pegargiminase)
    4ms
    Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC) (clinicaltrials.gov)
    P1/2, N=30, Recruiting, M.D. Anderson Cancer Center | Suspended --> Recruiting
    Enrollment open
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
    |
    TP53 mutation • PTEN mutation • LDH elevation
    |
    carboplatin • cabazitaxel • Hepacid (pegargiminase)
    4ms
    MYC-ATF4-ASS1 axis governs intracellular arginine synthesis and dictates the immune microenvironment in melanoma. (PubMed, bioRxiv)
    ATF4 knockout in melanoma cells phenocopied ASS1 knockout in the same cells, both showing greater sensitivity to arginine depletors such as ADI-PEG20...Single cell transcriptomics profiled the reshaped tumor microenvironment and revealed that a subset of resident macrophages were reprogrammed by endogenous arginine blockade. Overall, our findings reveal that the MYC-ATF4-ASS1 axis not only controls arginine vulnerability of melanomas but also shapes the immune microenvironment.
    Journal
    |
    CD8 (cluster of differentiation 8) • ASS1 (Argininosuccinate synthase 1) • ATF4 (Activating Transcription Factor 4)
    |
    Hepacid (pegargiminase)
    5ms
    Phase I/II Study of PEGylated Arginine Deiminase (ADI-PEG20) With Carboplatin and Cabazitaxel in Men With Aggressive Variant Prostate Cancers (AVPC) (clinicaltrials.gov)
    P1/2, N=30, Suspended, M.D. Anderson Cancer Center | Recruiting --> Suspended
    Trial suspension
    |
    TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1)
    |
    TP53 mutation • PTEN mutation • LDH elevation
    |
    carboplatin • cabazitaxel • Hepacid (pegargiminase)
    6ms
    Neoadjuvant ADI-PEG 20 + Ifosfamide + Radiotherapy in Soft Tissue Sarcoma (clinicaltrials.gov)
    P1, N=6, Active, not recruiting, Washington University School of Medicine | Phase classification: P1/2 --> P1 | N=35 --> 6 | Trial completion date: Jan 2029 --> Mar 2028 | Trial primary completion date: Jan 2027 --> Mar 2026 | Recruiting --> Active, not recruiting
    Enrollment closed • Phase classification • Enrollment change • Trial completion date • Trial primary completion date
    |
    ifosfamide • Hepacid (pegargiminase) • mesna
    6ms
    ADI-PEG 20 in Combination With Gemcitabine and Docetaxel After Progression on Frontline Therapy in Non-small Cell and Small Cell Lung Cancers (clinicaltrials.gov)
    P1/2, N=31, Active, not recruiting, Washington University School of Medicine | N=114 --> 31 | Recruiting --> Active, not recruiting
    Enrollment closed • Enrollment change
    |
    EGFR (Epidermal growth factor receptor) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS)
    |
    EGFR mutation
    |
    gemcitabine • docetaxel • Hepacid (pegargiminase)
    6ms
    POLARIS2020-002: Study of ADI-PEG 20, Venetoclax and Azacitidine in Acute Myeloid Leukemia (clinicaltrials.gov)
    P1, N=38, Active, not recruiting, Polaris Group | Trial completion date: Jul 2026 --> Dec 2026 | Trial primary completion date: Dec 2025 --> May 2026
    Trial completion date • Trial primary completion date
    |
    Venclexta (venetoclax) • azacitidine • Hepacid (pegargiminase)