Skip to main content
drug_type
RELEVANT_DRUG
intervention_type
Biological
drug_description
Investigational tetra-specific (multispecific) antibody biologic given by weekly IV infusion for relapsed/refractory B-cell malignancies (CLL/SLL and other NHL); designed to bind multiple antigens to enhance immune-mediated killing and reduce antigen escape.
nci_thesaurus_concept_id
C183545
nci_thesaurus_definition
An anti-ROR1/anti-CD3/anti-PD-L1/anti-4-1BB tetra-specific antibody, with potential immunostimulatory and antineoplastic activities. Upon administration, nebratamig targets and binds to the tumor-associated antigen (TAA) receptor tyrosine kinase-like orphan receptor 1 (ROR1), the immunosuppressive ligand programmed cell death-1 ligand 1 (PD-L1; cluster of differentiation 274; CD274) expressed on tumor cells, the T-cell surface antigen CD3 and the costimulatory receptor 4-1BB (CD137; tumor necrosis factor receptor superfamily member 9; TNFRSF9) expressed on a variety of leukocyte subsets including activated T-lymphocytes. This may crosslink ROR1-expressing tumor cells and cytotoxic T-lymphocytes (CTLs) and result in a potent CTL-mediated cell lysis of ROR1-expressing tumor cells. In addition, 4-1BB binding results in T-cell co-stimulation and enhanced anti-tumor activity. At the same time, GNC-035 prevents PD-L1 from binding to and activating its receptor, programmed cell death 1 (PD-1; PDCD1; CD279; programmed death-1). This abrogates T-cell inhibition, activates antigen-specific T-lymphocytes and enhances CTL-mediated tumor cell lysis, which may lead to a reduction in tumor growth. PD-L1 binding to PD-1 on activated T-cells inhibits the expansion and survival of CD8-positive T-cells, suppresses the immune system and results in immune evasion. 4-1BB, a surface glycoprotein of the tumor necrosis factor receptor superfamily, is an inducible costimulatory receptor that plays a key role in T-cell proliferation, survival and cytolytic activity. ROR1, also known as neurotrophic tyrosine kinase, receptor-related 1 (NTRKR1), is expressed during embryogenesis and in many types of hematological malignancies. It plays key roles in tumor cell proliferation and survival.
drug_mesh_term
Antibodies, Bispecific
drug_category
TRISPECIFIC T ENGAGER
drug_class
Engager
drug_delivery_route
Intravenous
drug_mechanism_of_action
Tetra-specific T‑cell–engaging antibody that binds ROR1 on tumor cells and CD3 on T cells to redirect cytotoxic T lymphocytes, while simultaneously blocking PD-L1 to relieve PD-1–mediated inhibition and agonizing 4-1BB to provide costimulation. The combined actions enhance T-cell activation and CTL-mediated lysis of ROR1+ malignant B cells and help mitigate antigen escape.
drug_name
GNC-035
nct_id_drug_ref
NCT05944978