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 protens, mediating mitogenic signals from IGF1R, IR, IL4R and other oncogenes, overexpressed in multiple tumor types
  • Regulates major survival pathways such as the PI3K/AKT, MEK/ERK and Wnt/β-cetenin
  • Activated as feedback response to anti-cancer therapies

STAT3

  • Well-established transcription factor associated with the tumorigenic phenotype
  • Provides a crucial axis to support cell proliferation and survival
  • Active in tumor JAK/STAT3 and TGF beta resistance mechanisms

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

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