drug_type
RELEVANT_DRUG
intervention_type
Radiopharmaceutical (therapeutic alpha therapy)
drug_description
Actinium-225–conjugated FPI-2053 targeted alpha therapy that binds EGFR/cMET and delivers high-LET alpha radiation causing DNA double-strand breaks and tumor cell kill.
nci_thesaurus_concept_id
C206445
nci_thesaurus_preferred_term
Actinium Ac 225 FPI-2068
nci_thesaurus_definition
A radioimmunoconjugate composed of FPI-2053, a humanized bispecific antibody targeting epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (HGFR; c-Met), chelated to the bifunctional, macrocyclic chelating agent tetra-azacyclododecanetetra-acetic acid (DOTA), and radiolabeled with the alpha-emitting radionuclide actinium Ac 225, with potential antineoplastic activity. Upon administration of actinium Ac 225 FPI-2068, the FPI-2053 moiety targets and binds to the extracellular domains of both EGFR and c-Met expressed on certain cancer cells, thereby delivering a cytotoxic dose of alpha radiation directly into EGFR- and c-Met-expressing tumor cells. Additionally, the induction of apoptosis and subsequent release of tumor-associated antigens (TAAs) from the tumor cells may induce an anti-tumor immune response, thereby further killing tumor cells. EGFR and c-Met, both upregulated or mutated in a variety of tumor cell types, play key roles in tumor cell proliferation. EGFR and c-Met are co-expressed on the surface of various cancer cell types while co-expression on normal, healthy cells is minimal.
drug_mesh_term
Radiopharmaceuticals
drug_category
RADIOIMMUNOCONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
Bispecific anti-EGFR/c-MET humanized antibody (FPI-2053) chelated to DOTA and radiolabeled with actinium-225; targets EGFR/c-MET on tumor cells and delivers high-LET alpha radiation that causes DNA double-strand breaks and tumor cell death, with potential secondary anti-tumor immune activation from antigen release.
drug_name
[225Ac]-FPI-2068
nct_id_drug_ref
NCT06147037