anti-OX40 antibody BMS 986178 Advanced Drug Monograph

Medication Report: anti-OX40 antibody BMS 986178

Name: anti-OX40 antibody BMS 986178 Name (English): anti-OX40 antibody BMS 986178 DrugBank ID: DB15773 Type: Biotech

Description: BMS-986178 is a fully human IgG1 agonistic monoclonal antibody that binds with high affinity to the OX40 receptor (CD134; TNFRSF4). OX40 is a co-stimulatory receptor expressed on T-lymphocytes that, upon activation, promotes the proliferation and survival of activated T-cells. BMS-986178 mimics the action of the endogenous OX40 ligand (OX40L), leading to the activation of the OX40 receptor. This activation can induce the proliferation of memory and effector T-lymphocytes and, in the presence of tumor-associated antigens (TAAs), may enhance an immune response against TAA-expressing tumor cells.

Mechanism of Action: As an agonist monoclonal antibody, BMS-986178 selectively binds to and activates the OX40 receptor on T-cells. This activation provides a co-stimulatory signal, promoting T-cell proliferation, differentiation into effector cells, and survival. In the context of cancer, this enhanced T-cell activity can potentially lead to an improved anti-tumor immune response.

Clinical Trials: BMS-986178 has been evaluated in clinical trials, both as a monotherapy and in combination with other immunotherapeutic agents such as nivolumab (anti-PD-1 antibody) and ipilimumab (anti-CTLA-4 antibody), in patients with advanced solid tumors and low-grade B-cell non-Hodgkin lymphomas. These trials have assessed the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and anti-tumor activity of the drug.

Safety and Efficacy: Clinical trial data suggest that BMS-986178, alone or in combination, generally has a manageable safety profile. Common treatment-related adverse events include fatigue, pruritus, rash, pyrexia, diarrhea, and infusion-related reactions. While preclinical studies showed promising anti-tumor activity, clinical efficacy as a monotherapy has been limited, and the added benefit in combination with checkpoint inhibitors has not been consistently significant across various tumor types.

Investigational Status: BMS-986178 is an investigational agent, and its role in cancer therapy continues to be explored in ongoing clinical studies.