^
    2ms
    Pembrolizumab, INCB081776, and Radiation Therapy for Head and Neck Squamous Cell Carcinoma (clinicaltrials.gov)
    P1, N=12, Not yet recruiting, University of Wisconsin, Madison
    New P1 trial • Checkpoint inhibition • Checkpoint block • Metastases
    |
    Keytruda (pembrolizumab) • INCB81776
    5ms
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1, N=84, Active, not recruiting, Incyte Corporation | Phase classification: P1a/1b --> P1 | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Nov 2023 --> Nov 2024
    Phase classification • Trial completion date • Trial primary completion date • Metastases
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation • FLT3 wild-type • IDH wild-type
    |
    Zynyz (retifanlimab-dlwr) • INCB81776
    10ms
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1a/1b, N=84, Active, not recruiting, Incyte Corporation | Recruiting --> Active, not recruiting | N=140 --> 84
    Enrollment closed • Enrollment change • Metastases
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation • FLT3 wild-type • IDH wild-type
    |
    Zynyz (retifanlimab-dlwr) • INCB81776
    1year
    Dual Axl/MerTK inhibitor INCB081776 creates a proinflammatory tumor immune microenvironment and enhances anti-PDL1 efficacy in head and neck cancer. (PubMed, Head Neck)
    This data indicates that simultaneous targeting of Axl and MerTK with INCB081776, either alone or in combination with anti-PDL1, slows tumor growth and creates a proinflammatory TIME in mouse models of HNC.
    Journal
    |
    AXL (AXL Receptor Tyrosine Kinase) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
    |
    AXL overexpression • MERTK expression
    |
    INCB81776
    almost2years
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1a/1b, N=140, Recruiting, Incyte Corporation | Trial completion date: May 2023 --> Sep 2023 | Trial primary completion date: May 2023 --> Aug 2023
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation • FLT3 wild-type • IDH wild-type
    |
    Zynyz (retifanlimab-dlwr) • INCB81776
    2years
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1a/1b, N=180, Recruiting, Incyte Corporation | Trial completion date: Sep 2022 --> May 2023 | Trial primary completion date: Sep 2022 --> May 2023
    Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation • FLT3 wild-type • IDH wild-type
    |
    Zynyz (retifanlimab-dlwr) • INCB81776
    2years
    Simultaneous inhibition of Axl and MerTK enhances anti-PDL1 efficacy and creates a pro-inflammatory tumor immune microenvironment in head and neck cancer (AACR 2022)
    Finally, the combination of INCB081776 and anti-PDL1 was superior to either treatment alone in slowing tumor growth. Together, these studies indicate that INCB081776 cooperates with anti-PDL1 in a syngeneic mouse model of HNC to slow tumor growth and create a pro-inflammatory environment, especially in immunologically cold tumors, thereby highlighting the potential clinical benefit of this therapeutic combination.
    Clinical
    |
    CD8 (cluster of differentiation 8) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
    |
    MERTK expression
    |
    INCB81776
    over3years
    A Potent and Selective Dual Inhibitor of AXL and MERTK Possesses Both Immunomodulatory and Tumor-Targeted Activity. (PubMed, Front Oncol)
    Finally, antitumor activity of INCB081776 was observed in a subset of sarcoma patient-derived xenograft models, which was linked with inhibition of phospho-AKT. These data support the potential therapeutic utility of INCB081776 as an immunotherapeutic agent capable of both enhancing tumor immune surveillance and blocking tumor cell survival mechanisms.
    Journal
    |
    CD8 (cluster of differentiation 8) • MERTK (MER Proto-Oncogene, Tyrosine Kinase)
    |
    INCB81776
    over3years
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1a/1b, N=140, Recruiting, Incyte Corporation | Trial completion date: Oct 2020 --> Aug 2022 | Trial primary completion date: Aug 2020 --> Aug 2022
    Clinical • Trial completion date • Trial primary completion date
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation
    |
    Zynyz (retifanlimab-dlwr) • INCB81776
    4years
    A Study Exploring the Safety and Tolerability of INCB081776 in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1a/1b, N=180, Recruiting, Incyte Corporation | N=93 --> 180
    Clinical • Enrollment change
    |
    FLT3 (Fms-related tyrosine kinase 3) • MSI (Microsatellite instability) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2)
    |
    MSI-H/dMMR • FLT3-ITD mutation
    |
    Zynyz (retifanlimab-dlwr) • INCB81776