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    DRUG:

    vocimagene amiretrorepvec/extended release flucytosine (DB107)

    i
    Other names: DB107, DB-107, DB 107, Toca 511/Toca FC, Toca511/Toca FC, Toca-511/Toca-FC, Toca 511, vocimagene amiretrorepvec-flucytosine gene therapy, ABC 511/FC
    Associations

    News

    Trials
    Company:
    ApolloBio, Denovo
    Drug class:
    Thymidylate synthase inhibitor, Cytosine deaminase inhibitor
    Related drugs:
    Associations

    News

    Trials
    2ms
    DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma (clinicaltrials.gov)
    P1/2, N=70, Not yet recruiting, Nicholas Butowski | Initiation date: Sep 2024 --> Dec 2024
    Trial initiation date • Combination therapy
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    MGMT (6-O-methylguanine-DNA methyltransferase)
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    temozolomide • vocimagene amiretrorepvec/extended release flucytosine (DB107)
    5ms
    Therapeutic activity of retroviral replicating vector-mediated gene therapy in combination with anti-PD-1 antibody in a murine pancreatic cancer model. (PubMed, Cancer Gene Ther)
    Toca 511, a tumor-selective retroviral replicating vector encoding the yeast cytosine deaminase (yCD) gene, exerts direct antitumor effects through intratumoral prodrug 5-fluorocytosine (5-FC) conversion to active drug 5-fluorouracil by yCD, and has demonstrated therapeutic efficacy in preclinical and clinical trials of various cancers. In an orthotopic tumor and peritoneal dissemination model, the combination therapy resulted in complete regression in both transduced orthotopic tumors and untransduced peritoneal dissemination. Thus, Toca 511/5-FC treatment induced a systemic antitumor immune response, and the combination therapy could be a promising clinical strategy for treating metastatic pancreatic cancer.
    Preclinical • Journal • Combination therapy • PD(L)-1 Biomarker • IO biomarker • Gene therapy
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    CD8 (cluster of differentiation 8)
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    5-fluorouracil • vocimagene amiretrorepvec/extended release flucytosine (DB107)
    5ms
    DB107-RRV, DB107-FC, and Radiation Therapy With or Without Temozolomide (TMZ) for High Grade Glioma (clinicaltrials.gov)
    P1/2, N=70, Not yet recruiting, Nicholas Butowski
    New P1/2 trial
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    MGMT (6-O-methylguanine-DNA methyltransferase)
    |
    temozolomide • vocimagene amiretrorepvec/extended release flucytosine (DB107)
    8ms
    DB107-Retroviral Replicating Vector (RRV) Combined With DB107-Flucytosine (FC) in Patients With Recurrent Glioblastoma or Anaplastic Astrocytoma (clinicaltrials.gov)
    P2, N=33, Recruiting, Ashish Shah | Not yet recruiting --> Recruiting
    Enrollment open
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    vocimagene amiretrorepvec/extended release flucytosine (DB107)
    10ms
    A Biomarker-Guided Phase 2 Study of DB107-Retroviral Replicating Vector (RRV) Combined With DB107-Flucytosine (FC) Extended-Release Tablets (clinicaltrials.gov)
    P2, N=33, Not yet recruiting, Ashish Shah
    New P2 trial
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    vocimagene amiretrorepvec/extended release flucytosine (DB107)
    over3years
    Current evidence and challenges of systematic therapies for adult recurrent glioblastoma: Results from clinical trials. (PubMed, Chin J Cancer Res)
    Regorafenib, rindopepimut and neoadjuvant programmed death 1 (PD-1) inhibitors are promising agents for rGBM, while regorafenib is effective in both O-methylguanine DNA methyltransferase (MGMT) promoter methylated and unmethylated patients. Temozolomide rechallenge and alkylating agents combined with bevacizumab can be useful for patients with MGMT methylation, and patients with isocitrate dehydrogenase (IDH) mutations or second recurrence can benefit from vocimagene amiretrorepvec (Toca 511). Some phase I trials on targeted therapy and immunotherapy have shown positive results, and results from further studies are expected. In addition to the analysis of existing clinical trial results, forthcoming trials should be well designed, and patients are encouraged to participate in appropriate clinical trials.
    Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
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    MGMT (6-O-methylguanine-DNA methyltransferase)
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    Avastin (bevacizumab) • temozolomide • Stivarga (regorafenib) • Rintega (rindopepimut) • vocimagene amiretrorepvec/extended release flucytosine (DB107)
    4years
    Effect of Vocimagene Amiretrorepvec in Combination With Flucytosine vs Standard of Care on Survival Following Tumor Resection in Patients With Recurrent High-Grade Glioma: A Randomized Clinical Trial. (PubMed, JAMA Oncol)
    For the SOC control group, patients received investigators' choice of single therapy: lomustine, temozolomide, or bevacizumab. Among patients who underwent tumor resection for first or second recurrence of glioblastoma or anaplastic astrocytoma, administration of Toca 511 and Toca FC, compared with SOC, did not improve overall survival or other efficacy end points. ClinicalTrials.gov Identifier: NCT02414165.
    Clinical • Journal • Combination therapy
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    IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
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    Avastin (bevacizumab) • temozolomide • lomustine • vocimagene amiretrorepvec/extended release flucytosine (DB107)
    almost5years
    A Study of Toca 511, a Retroviral Replicating Vector, Combined With Toca FC in Patients With Solid Tumors or Lymphoma (Toca 6) (clinicaltrials.gov)
    P1b, N=21, Terminated, Tocagen Inc. | N=30 --> 21 | Active, not recruiting --> Terminated; Sponsor decision
    Clinical • Enrollment change • Trial termination
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    KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FLT3 (Fms-related tyrosine kinase 3) • NRAS (Neuroblastoma RAS viral oncogene homolog) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • KEAP1 (Kelch Like ECH Associated Protein 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • RUNX1 (RUNX Family Transcription Factor 1) • ASXL1 (ASXL Transcriptional Regulator 1) • KDR (Kinase insert domain receptor) • TET2 (Tet Methylcytosine Dioxygenase 2) • KMT2D (Lysine Methyltransferase 2D) • PTCH1 (Patched 1) • MSH6 (MutS homolog 6) • CDK12 (Cyclin dependent kinase 12) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11) • NOTCH2 (Notch 2) • KDM6A (Lysine Demethylase 6A) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • PIK3CB (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) • STAG2 (Stromal Antigen 2) • NSD1 (Nuclear Receptor Binding SET Domain Protein 1) • MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) • SOX9 (SRY-Box Transcription Factor 9) • DICER1 (Dicer 1 Ribonuclease III) • PIK3C2B (Phosphatidylinositol-4-Phosphate 3-Kinase Catalytic Subunit Type 2 Beta) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • CHD4 (Chromodomain Helicase DNA Binding Protein 4) • GATA3 (GATA binding protein 3)
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    IDH1 mutation • KEAP1 mutation • MGMT promoter methylation • PTCH1 mutation • STAG2 mutation • MGMT mutation
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    vocimagene amiretrorepvec/extended release flucytosine (DB107)