drug_type
RELEVANT_DRUG
intervention_type
Antibody–Drug Conjugate (Drug)
drug_description
An anti–PD-L1 antibody–drug conjugate administered IV every 3 weeks. The monoclonal antibody blocks the PD-1/PD-L1 immune checkpoint to restore T-cell antitumor activity and, after PD-L1–mediated internalization, releases a DNA topoisomerase I inhibitor payload that induces DNA damage, replication stress, and apoptosis in PD-L1–expressing cells.
nci_thesaurus_concept_id
C204168
nci_thesaurus_definition
An antibody-drug conjugate (ADC) composed of a humanized immunoglobulin G1 (IgG1) monoclonal antibody directed against the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274), conjugated, via a cleavable linker, to a cytotoxic payload containing a camptothecin-based topoisomerase I (topo I) inhibitor, with potential antineoplastic activity. Upon administration of the anti-PD-L1 ADC HLX43, the anti-PD-L1 antibody moiety specifically targets and binds to PD-L1 expressed on tumor cells. The linker is specifically cleaved in the tumor microenvironment (TME), thereby delivering the toxin into PD-L1-expressing malignant cells, while sparing the normal cells. The cytotoxic agent specifically inhibits DNA topoisomerase I activity, causes double-strand breaks (DSBs) of DNA, and thereby inhibiting DNA replication and resulting in tumor cell apoptosis. This inhibits the proliferation of PD-L1-expressing tumor cells. In addition, HLX43 induces bystander killing effects, thereby further decreasing PD-L1-expessing tumor cells. PD-L1, a transmembrane protein, is expressed on the surface of certain immune cells and on many cancer cell types. PD-L1 binding to PD-1, a negative regulator of the immune system on activated T-cells, limits the expansion and survival of CD8-positive T-cells, suppresses the immune system and results in immune evasion.
drug_category
ANTIBODY DRUG CONJUGATE
drug_class
Conjugate
drug_delivery_route
Intravenous
drug_mechanism_of_action
HLX43 is an anti-PD-L1 IgG1 antibody–drug conjugate that both blocks the PD-1/PD-L1 immune checkpoint to restore T-cell antitumor activity and, after PD-L1–mediated internalization and linker cleavage, releases a camptothecin-based topoisomerase I inhibitor payload that causes DNA damage, replication stress, and apoptosis in PD-L1–expressing cells (with potential bystander killing).
drug_name
HLX43
nct_id_drug_ref
NCT06115642