Elzovantinib

Elzovantinib (TPX-0022) is an orally bioavailable multi-targeted kinase inhibitor with a novel macrocyclic structure that inhibits the MET, CSF1R (colony stimulating factor 1 receptor) and SRC kinases. Elzovantinib is being evaluated in the ongoing SHIELD-1 clinical trial in patients with MET-driven advanced solid tumors. Elzovantinib is an orally bioavailable multi-targeted kinase inhibitor with a novel macrocyclic structure that inhibits the MET, CSF1R (colony stimulating factor 1 receptor) and SRC kinases. Elzovantinib is being evaluated in the ongoing SHIELD-1 clinical trial in patients with MET-driven advanced solid tumors.

What are the latest updates on Elzovantinib?

Preliminary interim data of elzovantinib (TPX-0022), a novel inhibitor of MET/SRC/CSF1R, in patients with advanced solid tumors harboring genetic alterations in MET: Update form the Phase 1 SHIELD-1 trial Source: AACR-NCI-EORTC 2021 Virtual International Conference on Molecular Targets and Cancer Therapeutics

Designed to be Different.

MET is a receptor tyrosine kinase that binds with high affinity to hepatocyte growth factor (HGF). MET alterations, including point mutations, amplifications, fusions, exon 14 skipping, and the generation of HGF-MET autocrine loops have been reported in approximately 3-5% of patients with NSCLC or gastric cancer. MET amplification has been detected in 15-20% of NSCLC patients with EGFR mutations who acquired resistance to Iressa (gefitinib), Tarceva (erlotinib) or Tagrisso (osimertinib) treatment.

SRC is a kinase involved in the MET signaling pathway. Inhibition of SRC has the potential to reduce or abolish the upregulation of HGF.

Targeting CSF1R leads to the modulation of tumor-associated macrophages (TAMs), a type of immune cell that suppresses the T-cell mediated anti-tumor immune response. Inhibition of CSF1R with elzovantinib may be a promising therapeutic strategy as a single agent or in combination with standard of care chemotherapy and immunotherapy in various solid tumors.

We believe the simultaneous inhibition of MET, SRC and CSF1R kinases is a promising strategy for the treatment of MET-driven solid tumors.

Elzovantinib Development Designations

Fast Track designation by the FDA in patients with MET amplified advanced or metastatic gastric cancer or GEJ adenocarcinoma after prior chemotherapy

Elzovantinib was also granted Orphan Drug designation in 2021 for the treatment of gastric cancer, including gastroesophageal junction adenocarcinoma.