drug_type
RELEVANT_DRUG
intervention_type
Drug
drug_description
Investigational immunotherapy drug administered as a short-term intravenous infusion; specific mechanism, target, and modality not disclosed. Studied as monotherapy in a Phase 1 first-in-human dose-escalation and expansion trial for adults with advanced solid tumors.
nci_thesaurus_concept_id
C200047
nci_thesaurus_preferred_term
Anti-CDH3/MSLN BiTE Antibody AMG 305
nci_thesaurus_definition
A dual-targeting bispecific antibody and T-cell engager (BiTE) co-targeting both the human tumor-associated antigens (TAAs) cadherin-3 (CDH3; placental cadherin; P-cadherin) and mesothelin (MSLN) on tumor cells and CD3 antigen found on T-lymphocytes, with potential immunostimulating and antineoplastic activities. Upon administration, anti-CDH3/MSLN BiTE antibody AMG 305 binds with specificity to tumor cells co-expressing CDH3 and MSLN antigens and CD3 on cytotoxic T-lymphocytes (CTLs). This results in the cross-linking of T-cells and tumor cells, and induces a cytotoxic T-lymphocyte (CTL) response against CDH3- and MSLN-co-expressing tumor cells. CDH3 is a member of the cadherin family; it is overexpressed in a variety of tumors and plays a role in cell adhesion, motility, invasion, and proliferation. Mesothelin, a cell surface glycoprotein involved in cell adhesion, is overexpressed in a variety of cancer cell types. Binding of both CDH3 and MSLN allows for increased specificity in targeting these TAAs that may be expressed at low levels on the tumor surface while limiting activity against normal cells that express only one of the target antigens.
drug_category
BISPECIFIC T ENGAGER
drug_class
Engager
drug_delivery_route
Intravenous
drug_mechanism_of_action
AMG 305 is a T‑cell–engaging bispecific antibody that binds CD3 on cytotoxic T cells and simultaneously recognizes the tumor-associated antigens cadherin‑3 (CDH3) and mesothelin (MSLN) on tumor cells. By crosslinking T cells to tumor cells co‑expressing CDH3 and MSLN, it activates T‑cell cytotoxicity and promotes selective lysis of dual‑positive tumor cells, improving specificity and limiting activity against normal tissues expressing only one antigen.
drug_name
AMG 305
nct_id_drug_ref
NCT05800964