Tiragolumab (DB16409): A Comprehensive Clinical and Scientific Analysis of a First-in-Class Anti-TIGIT Immunotherapy

Executive Summary

Tiragolumab (DrugBank ID: DB16409) is an investigational, first-in-class, fully human immunoglobulin G1 (IgG1) monoclonal antibody targeting the T-cell immunoreceptor with Ig and ITIM domains (TIGIT), an inhibitory immune checkpoint.[1] Developed by Genentech, a member of the Roche Group, tiragolumab was designed to function as an immune amplifier, primarily in combination with the anti-PD-L1 antibody atezolizumab, to synergistically reinvigorate the anti-tumor immune response.[4] The scientific rationale is predicated on the complementary roles of the TIGIT and PD-L1/PD-1 pathways in mediating T-cell exhaustion, with dual blockade hypothesized to produce a more profound and durable anti-cancer effect than targeting either pathway alone.[7]

The initial clinical development of tiragolumab was highly promising. The Phase II CITYSCAPE trial demonstrated clinically meaningful improvements in objective response rate (ORR) and progression-free survival (PFS) for the tiragolumab-atezolizumab combination in first-line, PD-L1-positive non-small cell lung cancer (NSCLC), particularly within a subgroup of patients with high PD-L1 expression.[9] These encouraging results led the U.S. Food and Drug Administration (FDA) to grant tiragolumab Breakthrough Therapy Designation in 2021, positioning it as the leading candidate in the burgeoning TIGIT inhibitor class.[4]