^
    6ms
    NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P1/2, N=29, Recruiting, University of Colorado, Denver | Not yet recruiting --> Recruiting
    Enrollment open
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    PD-L1 (Programmed death ligand 1)
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    Keytruda (pembrolizumab) • Erbitux (cetuximab) • NT219
    8ms
    NT219 Combined With Standard of Care Biologic Therapy in Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P1/2, N=29, Not yet recruiting, University of Colorado, Denver
    New P1/2 trial
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    PD-L1 (Programmed death ligand 1)
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • NT219
    10ms
    IRS2 as a driver of brain metastasis in colorectal cancer: a potential target for novel therapeutic strategies. (PubMed, Neuro Oncol)
    Our work underscores the unique role of IRS2 in facilitating CRC brain adaptation and suggests a novel therapeutic strategy for CRC patients with BM.
    Journal
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    CTNNB1 (Catenin (cadherin-associated protein), beta 1) • IRS2 (Insulin receptor substrate 2)
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    5-fluorouracil • NT219
    1year
    A Study to Evaluate NT219 Alone and in Combination with ERBITUX® (Cetuximab) in Adults with Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=52, Completed, TyrNovo Ltd. | Active, not recruiting --> Completed | N=110 --> 52
    Trial completion • Enrollment change • Combination therapy • Metastases
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
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    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
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    Erbitux (cetuximab) • NT219
    over1year
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Active, not recruiting, TyrNovo Ltd. | Trial completion date: Sep 2024 --> Jun 2024
    Trial completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    almost2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Active, not recruiting, TyrNovo Ltd. | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    almost2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Recruiting, TyrNovo Ltd.
    Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    2years
    A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer (clinicaltrials.gov)
    P1/2, N=110, Recruiting, TyrNovo Ltd. | N=75 --> 110 | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Jun 2023 --> Jun 2024
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene)
    |
    KRAS wild-type • RAS wild-type • RAS wild-type + BRAF wild-type
    |
    Erbitux (cetuximab) • NT219
    over2years
    NT219 induces tumor PD-L1 expression and potentiates anti-PD-1 efficacy (AACR 2023)
    In addition, to evaluate the combination effect of NT219 with ICB therapy in ICB-resistant PDX model, we used a humanized PDX model of pembrolizumab-resistant gastroesophageal tumor (GEJ). To summarize, we found a significant synergistic effect of NT219 combined with anti-PD-1 therapy, supported by a mechanism of PDL-1 induction making ICB resistant tumors amenable to ICB treatment. Collectively, these findings demonstrated that NT219 has the potential to reverse ICB resistance in both human PDX and murine syngeneic tumor model systems
    Clinical • PD(L)-1 Biomarker • IO biomarker
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    PD-L1 (Programmed death ligand 1)
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    PD-L1 expression • BRAF mutation
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    Keytruda (pembrolizumab) • NT219
    over3years
    IRS1 phosphorylation underlies the non-stochastic probability of cancer cells to persist during EGFR inhibition therapy. (PubMed, Nat Cancer)
    Indeed, the first-in-class IRS1 inhibitor NT219 was highly synergistic with anti-epidermal growth factor receptor therapy across multiple in vitro and in vivo models. Elucidation of drug-specific mechanisms that determine the degree and stability of cellular CTP may establish a framework for the elimination of cancer persisters, using new rationally designed drug combinations.
    Journal
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    EGFR (Epidermal growth factor receptor) • IRS1 (Insulin Receptor Substrate 1)
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    NT219