The once-hyped immuno-oncology target TIGIT has encountered significant setbacks, with leading drugs like BeOne Medicines’ ociperlimab and GSK’s belrestotug discontinued after disappointing clinical trial results in non-small cell lung cancer. Despite initial enthusiasm sparked by Roche’s phase 2 data, multiple phase 3 trials have failed to demonstrate clear clinical benefits over existing therapies. Analysts attribute these failures to overestimation of early-phase outcomes, inappropriate trial designs, and suboptimal drug formats, underlining risks in immuno-oncology R&D and the costly $6 billion wager made by Big Pharma on this modality. The experience highlights the need for better predictive markers and strategic drug development in the checkpoint inhibitor space.