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    DRUG:

    tegavivint (BC2059)

    i
    Other names: BC2059, BC 2059, BC-2059, NSC#826393, APL-121
    Company:
    Apollomics, Iterion Therap
    Drug class:
    β-catenin inhibitor, Wnt signalling pathway inhibitor
    Related drugs:
    3ms
    Tegavivint With Gemcitabine in Patients With Relapsed or Refractory Osteosarcoma (clinicaltrials.gov)
    P1, N=24, Not yet recruiting, Emory University
    New P1 trial
    |
    gemcitabine • tegavivint (BC2059)
    7ms
    A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov)
    P1/2, N=178, Recruiting, Iterion Therapeutics | N=108 --> 178
    Enrollment change
    |
    AXIN1 (Axin 1)
    |
    Lenvima (lenvatinib) • Cabometyx (cabozantinib tablet) • tegavivint (BC2059)
    9ms
    Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma. (PubMed, Blood Adv)
    Combining tegavivint with PARP-1/2 inhibitor talazoparib results in synergistic MCL cell death in vitro, and in vivo this combination significantly prolonging the survival of an MCL PDX. Together, our results define the role of TBL1X in maintaining genomic stability in MCL and establish targeting TBL1X as a novel therapeutic strategy for patients with this incurable disease.
    Journal • PARP Biomarker
    |
    CCND1 (Cyclin D1) • RAD51 (RAD51 Homolog A)
    |
    Talzenna (talazoparib) • tegavivint (BC2059)
    10ms
    Tegavivint for the Treatment of Relapsed or Refractory Leukemia (clinicaltrials.gov)
    P1, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025
    Trial completion date • Trial primary completion date
    |
    decitabine • tegavivint (BC2059)
    11ms
    Osimertinib and Tegavivint As First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | N=18 --> 24 | Trial completion date: Dec 2024 --> Jul 2029 | Trial primary completion date: Dec 2024 --> Jul 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • tegavivint (BC2059)
    11ms
    Osimertinib and Tegavivint As First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=24, Recruiting, Ohio State University Comprehensive Cancer Center | N=18 --> 24 | Trial completion date: Dec 2024 --> Jul 2029 | Trial primary completion date: Dec 2024 --> Jul 2025
    Enrollment change • Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • tegavivint (BC2059)
    almost2years
    Cytosolic Cadherin 4 promotes angiogenesis and metastasis in papillary thyroid cancer by suppressing the ubiquitination/degradation of β-catenin. (PubMed, J Transl Med)
    CDH4 induces PTC angiogenesis and metastasis via the inhibition of β-TrCP1-dependent ubiquitination of β-Catenin.
    Journal
    |
    CTNNB1 (Catenin (cadherin-associated protein), beta 1)
    |
    tegavivint (BC2059)
    almost2years
    Tegavivint for the Treatment of Relapsed or Refractory Leukemia (clinicaltrials.gov)
    P1, N=9, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | N=54 --> 9 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024
    Enrollment closed • Enrollment change • Trial completion date • Trial primary completion date
    |
    decitabine • tegavivint (BC2059)
    almost2years
    Osimertinib and Tegavivint as First-Line Therapy for the Treatment of Metastatic EGFR-Mutant Non-small Cell Lung Cancer (clinicaltrials.gov)
    P1, N=18, Recruiting, Ohio State University Comprehensive Cancer Center | Trial primary completion date: Dec 2023 --> Dec 2024
    Trial primary completion date • Metastases
    |
    EGFR (Epidermal growth factor receptor) • NOTCH3 (Notch Receptor 3)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR L861Q • EGFR G719X • EGFR S768I
    |
    Tagrisso (osimertinib) • tegavivint (BC2059)
    almost2years
    Preclinical efficacy of targeting epigenetic mechanisms in AML with 3q26 lesions and EVI1 overexpression. (PubMed, Leukemia)
    Tegavivint (TV, BC-2059), known to disrupt the binding of nuclear β-catenin and TCF7L2/LEF1 with TBL1, also inhibited co-localization of EVI1 with TBL1 and dose-dependently induced apoptosis in AML cell lines and patient-derived (PD) AML cells with 3q26.2 lesions. TV treatment repressed EVI1, attenuated enhancer activity at ERG, TCF7L2, GATA2 and MECOM loci, abolished interactions between MYC enhancers, repressing AML stemness while upregulating mRNA gene-sets of interferon/inflammatory response, TGF-β signaling and apoptosis-regulation. Co-treatment with TV and BETi or venetoclax induced synergistic in vitro lethality and reduced AML burden, improving survival of NSG mice harboring xenografts of AML with 3q26.2 lesions.
    Preclinical • Journal
    |
    MYC (V-myc avian myelocytomatosis viral oncogene homolog) • MCL1 (Myeloid cell leukemia 1) • CDK4 (Cyclin-dependent kinase 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • GATA2 (GATA Binding Protein 2) • TCF7L2 (Transcription Factor 7 Like 2) • TGFB1 (Transforming Growth Factor Beta 1) • BRD4 (Bromodomain Containing 4)
    |
    Venclexta (venetoclax) • tegavivint (BC2059)
    2years
    Actionable Findings from an Unbiased Drug Screen for Novel Single Agent and Combination Therapies Against AML with Mecom Re-Arrangement (ASH 2023)
    This was consistent with previous reports that BET inhibitors (e.g., OTX015, mivebresib or ABBV-075 and JQ1) are effective against 3q26.2-r AML cell lines, patient-derived (PD) AML cells and PDX models...In follow-up experiments, XIAP/cIAPs inhibitors birinapant (10-1000 nM) or SM-164 (30-1000 nM), chosen based on the MIPE screen outcomes, induced significantly more dose-dependent apoptosis in 3q26.2-r versus the other AML cell lines...Treatment with the dual mTOR/PIK3CA inhibitor NVP-BGT226 (1-30 nM) or navitoclax or Bcl-xL-specific BH3 mimetic A-1155463 also exerted lethality and synergistically induced apoptosis with mivebresib in AML cells with inv3/t(3; 3)...Co-treatment with birinapant and tegavivint also synergistically induced apoptosis in 3q26.2-r AML cells...Additionally, compared to each drug or vehicle control, co-treatment with birinapant and the BETi OTX015 (30 mg/kg/day, by oral gavage) was more effective in reducing AML burden in the xenograft model. These findings demonstrate promising preclinical activity of IAP protein inhibition against the cellular models of AML with inv3/t(3; 3) with EVI1 overexpression, supporting the rationale to further evaluate in vivo efficacy of birinapant and/or BETi-based combinations against this AML sub-type.
    Combination therapy • PARP Biomarker
    |
    PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • SF3B1 (Splicing Factor 3b Subunit 1) • MCL1 (Myeloid cell leukemia 1) • CDK4 (Cyclin-dependent kinase 4) • BCL2L1 (BCL2-like 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MECOM (MDS1 And EVI1 Complex Locus) • CASP3 (Caspase 3) • GATA2 (GATA Binding Protein 2) • BRD4 (Bromodomain Containing 4) • XIAP (X-Linked Inhibitor Of Apoptosis) • HEXIM1 (HEXIM P-TEFb Complex Subunit 1)
    |
    RAS mutation • SF3B1 mutation
    |
    JQ-1 • navitoclax (ABT 263) • birabresib (OTX015) • birinapant (IGM-9427) • mivebresib (ABBV 075) • tegavivint (BC2059) • BGT226 • SM-164
    2years
    A Study of Tegavivint (BC2059) in Patients With Advanced Hepatocellular Carcinoma (clinicaltrials.gov)
    P1/2, N=108, Recruiting, Iterion Therapeutics | Not yet recruiting --> Recruiting | Initiation date: May 2023 --> Sep 2023
    Enrollment open • Trial initiation date • Metastases
    |
    AXIN1 (Axin 1)
    |
    CTNNB1 mutation
    |
    Keytruda (pembrolizumab) • tegavivint (BC2059)