Vibostolimab (MK-7684): A Comprehensive Report on the Scientific Rationale, Clinical Development, and Discontinuation of an Anti-TIGIT Immunotherapy

1.0 Executive Summary

Vibostolimab, also known as MK-7684, was a humanized IgG1 monoclonal antibody developed by Merck & Co., Inc., as an investigational immunotherapy targeting the T-cell immunoreceptor with immunoglobulin and ITIM domains (TIGIT). Positioned as a next-generation immune checkpoint inhibitor, its development was underpinned by a strong preclinical rationale suggesting it could overcome tumor-induced immune suppression by blocking the inhibitory TIGIT pathway. A central component of Merck's strategy was the development of vibostolimab as a fixed-dose co-formulation with its cornerstone anti-PD-1 therapy, pembrolizumab (KEYTRUDA®), a combination intended to offer synergistic anti-tumor activity and administrative convenience.

Preclinical and structural analyses revealed that vibostolimab possessed potentially advantageous characteristics compared to other anti-TIGIT antibodies, such as tiragolumab. These included a larger binding footprint on the TIGIT protein, complete competition with the primary ligand CD155, and distinct binding kinetics that translated to superior T-cell activation in in vitro assays. Based on these promising early signals, Merck launched the ambitious KEYVIBE clinical development program, a comprehensive series of nine trials designed to evaluate vibostolimab-based therapies in over 4,000 patients across a wide spectrum of solid tumors and hematological malignancies, including non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), and melanoma.