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NT219

Overview and Mechanism of Action

NT219 is a first-in-class, novel small molecule targeting both IRS1/2 and STAT3, important oncogenic drivers and major drug resistance pathways in many hard-to-treat cancers. In preclinical studies, NT219 demonstrated strong efficacy in preventing acquired resistance and reversing tumor resistance when administered as a monotherapy and in combination with various existing oncology therapies.

IRS1/2

  • Scaffold proteins, mediating mitogenic, metastatic, angiogenic and anti-apoptotic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumors
  • Regulates major survival pathways such as the PI3K/AKT, MEK/ERK and WNT/β-catenin
  • Activated as a feedback response to anti-cancer therapies
  • IRS plays an important role in promoting a tumor-protective microenvironment, by mediating upregulation of TAMs and CAFs

STAT3

  • Well-established transcription factor associated with the tumorigenic phenotype
  • STAT3 is broadly hyperactivated in many cancers, promoting proliferation, survival, angiogenesis and metastasis
  • STAT3 pathway is required for TGFβ-induced EMT and cancer cell migration and invasion
  • STAT3 is a critical player in tumor immune evasion, suppressing immune stimulators and enhancing immunosuppressive factors

Clinical Studies

A Phase 1/2 first-in-human clinical trial in the U.S. is ongoing, in which NT219 is used both as a monotherapy and in combination with cetuximab (Erbitux™), with plans to expand the combination study to include patients with recurrent or metastatic SCCHN cancer in 2021.

Study Design

Study Design Diagram

Dose Escalation Design

Dose Escalation Design Diagram
NT219 - References (Download)
ClinicalTrials.gov NCT04474470 - A Study to Evaluate NT219 Alone and in Combination With ERBITUX® (Cetuximab) in Adults With Advanced Solid Tumors and Head and Neck Cancer
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