To Top

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 study of NT219 is ongoing and currently we are advancing it in a dose escalation as a monotherapy treatment of solid tumors, and in a dose escalation in combination with cetuximab for the treatment of recurrent and metastatic squamous cell carcinoma of the head and neck (SCCHN) or colorectal adenocarcinoma (CRC). These studies will be followed by an expansion phase of NT219 at its recommended Phase 2 level in combination with cetuximab in patients with recurrent and metastatic SCCHN.

Study Design

Dose Escalation Design

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
Skip to content