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    BIOMARKER:

    LATS1 mutation

    i
    Other names: LATS1, Large Tumor Suppressor Kinase 1, WARTS, LATS (Large Tumor Suppressor, Drosophila) Homolog 1, Serine/Threonine-Protein Kinase LATS1, Large Tumor Suppressor Homolog 1, WARTS Protein Kinase, H-Warts, LATS, Large Tumor Suppressor, Homolog 1 (Drosophila), LATS, Large Tumor Suppressor, Homolog 1, Wts
    Entrez ID:
    9113
    2ms
    A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (clinicaltrials.gov)
    P1, N=156, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2025 --> Jan 2026 | Trial primary completion date: Oct 2025 --> Jan 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    LATS1 (Large Tumor Suppressor Kinase 1) • LATS2 (Large Tumor Suppressor Kinase 2)
    |
    LATS1 mutation • LATS2 mutation
    |
    IAG933
    8ms
    A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (clinicaltrials.gov)
    P1, N=156, Recruiting, Novartis Pharmaceuticals | Trial completion date: May 2025 --> Oct 2025 | Trial primary completion date: May 2025 --> Oct 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    LATS1 (Large Tumor Suppressor Kinase 1) • LATS2 (Large Tumor Suppressor Kinase 2)
    |
    LATS1 mutation • LATS2 mutation
    |
    IAG933
    9ms
    A Study of BPI-460372 in Advanced Solid Tumor Patients (clinicaltrials.gov)
    P1, N=82, Recruiting, Betta Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open
    |
    LATS1 (Large Tumor Suppressor Kinase 1)
    |
    LATS1 mutation
    |
    BPI-460372
    1year
    A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (clinicaltrials.gov)
    P1, N=156, Recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2024 --> May 2025 | Trial primary completion date: Sep 2024 --> May 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    LATS1 (Large Tumor Suppressor Kinase 1) • LATS2 (Large Tumor Suppressor Kinase 2)
    |
    LATS1 mutation • LATS2 mutation
    |
    IAG933
    over1year
    Phase 1 Study of BPI-460372 in Advanced Solid Tumor Patients (clinicaltrials.gov)
    P1, N=82, Not yet recruiting, Betta Pharmaceuticals Co., Ltd.
    New P1 trial • Metastases
    |
    LATS1 (Large Tumor Suppressor Kinase 1)
    |
    LATS1 mutation
    |
    BPI-460372
    2years
    Reciprocal positive regulation between BRD4 and YAP in GNAQ-mutant uveal melanoma cells confers sensitivity to BET inhibitors. (PubMed, Pharmacol Res)
    The transcriptional interdependency between BRD4 and YAP identified in Gq-mutated cells is responsible for the preferential inhibitory effect of BET inhibitors on the growth and dissemination of Gq-mutated UM cells compared to BRAF-mutated CM cells in both culture cells and animal models. Our findings suggest BRD4 as a viable therapeutic target for Gq-driven UMs that are addicted to unrestrained YAP function.
    Journal
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • GNAQ (G Protein Subunit Alpha Q) • GNA11 (G Protein Subunit Alpha 11) • BRD4 (Bromodomain Containing 4) • LATS1 (Large Tumor Suppressor Kinase 1)
    |
    BRAF mutation • NRAS mutation • GNAQ mutation • LATS1 mutation
    over2years
    The predictive value of LATS1 mutation for immune checkpoint inhibitors therapy in bladder cancer (ESMO 2022)
    Conclusions LATS1 mutations might be a potential biomarker to predict the efficacy of immunotherapy for bladder cancer. Considering the heterogeneity among the patients and other confounding factors, further prospective validation cohorts are warranted.
    Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
    |
    TMB (Tumor Mutational Burden) • LATS1 (Large Tumor Suppressor Kinase 1)
    |
    TMB-H • LATS1 mutation
    over2years
    Patients deriving long-term benefit from immune checkpoint inhibitors demonstrate conserved patterns of site-specific mutations. (PubMed, Sci Rep)
    Thus, this study identified several genes that may have utility as predictive biomarkers for therapeutic responses in patients receiving ICIs. As many have no known relationship to immunotherapy or ICIs, these genes warrant continued exploration, particularly for cancers in which established biomarkers such as PD-L1 expression or TMB have little predictive value.
    Retrospective data • Journal • Checkpoint inhibition • Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • RNF43 (Ring Finger Protein 43) • VHL (von Hippel-Lindau tumor suppressor) • CREBBP (CREB binding protein) • NOTCH3 (Notch Receptor 3) • ZFHX3 (Zinc Finger Homeobox 3) • EPHA7 (EPH Receptor A7) • LATS1 (Large Tumor Suppressor Kinase 1) • NCOA3 (Nuclear Receptor Coactivator 3)
    |
    PD-L1 expression • VHL mutation • CREBBP mutation • RNF43 mutation • NOTCH3 mutation • LATS1 mutation
    over2years
    A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (clinicaltrials.gov)
    P1, N=156, Recruiting, Novartis Pharmaceuticals | Trial completion date: May 2024 --> Sep 2024 | Trial primary completion date: May 2024 --> Sep 2024
    Trial completion date • Trial primary completion date
    |
    LATS1 (Large Tumor Suppressor Kinase 1) • LATS2 (Large Tumor Suppressor Kinase 2)
    |
    LATS1 mutation • LATS2 mutation
    3years
    A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (clinicaltrials.gov)
    P1, N=156, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    LATS1 (Large Tumor Suppressor Kinase 1) • LATS2 (Large Tumor Suppressor Kinase 2)
    |
    LATS1 mutation • LATS2 mutation