The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies
Creators: name: Shapira-Frommer, Ronnie
name: Niu, Jiaxin
name: Perets, Ruth
name: Peters, Solange
name: Shouse, Geoffrey
name: Lugowska, Iwona
name: Garassino, Marina C.
name: Sands, Jacob
name: Keenan, Tanya
name: Zhao, Bin
name: Healy, Jane
name: Ahn, Myung-Ju
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Space Science
subject: Medicine
subject: Pharmacology
subject: Chemical Sciences not elsewhere classified
subject: Immunology
subject: FOS: Clinical medicine
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Infectious Diseases
subject: FOS: Health sciences
subject: Computational Biology

description: Vibostolimab, a humanized IgG1 monoclonal antibody, blocks the interaction between TIGIT and its ligands, preventing the immunosuppressive effects of TIGIT. The addition of vibostolimab to the PD-1 inhibitor pembrolizumab has shown promising antitumor activity, warranting further exploration of vibostolimab as a potential therapeutic option. The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy in advanced solid tumors and hematological malignancies. These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease. The KEYVIBE program consisting of nine trials will evaluate the safety and efficacy of the anti-TIGIT antibody vibostolimab across several tumor types. <b>Trial registration:</b> KEYVIBE-001 (NCT02964013); KEYVIBE-002 (NCT04725188); KEYVIBE-003 (NCT04738487); KEYVIBE-004 (NCT05005442); KEYVIBE-005 (NCT05007106); KEYVIBE-006 (NCT05298423); KEYVIBE-007 (NCT05226598); KEYVIBE-008 (NCT05224141); and KEYVIBE-010 (NCT05665595) (ClinicalTrials.gov). Over the past decade, promising clinical efficacy has been observed with immune checkpoint inhibitors; however, there remains a subset of patients who do not respond or later develop resistance to treatment and experience tumor relapse. T-cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor that competitively inhibits the binding of the activating receptor CD226 with its ligands and is highly coexpressed with PD-L1. The binding of TIGIT to its ligands on tumor cells may contribute substantively to the suppression of T-cell signaling. Vibostolimab is a novel humanized IgG1 monoclonal antibody that blocks TIGIT from interacting with its ligands and engages the Fc-γ receptor on myeloid cells. Vibostolimab and the PD-1 inhibitor pembrolizumab exert their effects through different pathways within the immune response cascade, making the combination an attractive option for further evaluation. Early clinical data from the NSCLC cohort of the KEYVIBE-001 trial demonstrated promising antitumor activity and a favorable safety profile with sequentially administered vibostolimab plus pembrolizumab, leading to the development of the KEYVIBE program. The KEYVIBE program includes one phase I trial, three phase II trials, and five phase III trials investigating vibostolimab-based therapies in multiple solid tumor types and hematological malignancies and as various lines of therapy. The wide selection of patients across the KEYVIBE trials will allow for a broad understanding of the patient populations that are most likely to benefit from vibostolimab and the treatment setting where vibostolimab is most likely to improve patient outcomes. The evaluation of coformulated vibostolimab-based therapy may also provide a solution to the drug administration challenges that arise with combination therapies that require sequential administration or different administration schedules.