GSK and iTeos Abandon TIGIT Therapy, Joining Industry-Wide Trend

In a significant setback for the development of TIGIT-targeted cancer immunotherapies, GlaxoSmithKline (GSK) and iTeos Therapeutics have announced the discontinuation of their collaborative efforts on belrestotug. This decision comes in the wake of disappointing results from mid-stage clinical trials, adding to a growing list of failures in this once-promising drug class.

Underwhelming Efficacy in Key Cancer Types

The Phase II GALAXIES Lung-201 study, which evaluated belrestotug in combination with GSK's PD-1 inhibitor Jemperli (dostarlimab) for non-small cell lung cancer (NSCLC), failed to demonstrate clinically meaningful improvements in progression-free survival. While the trial met its primary endpoint of objective response rate, the lack of significant benefit in this crucial secondary outcome led to the therapy's termination.

Similarly, the GALAXIES H&N-202 Phase II study in head and neck squamous cell carcinoma showed results that fell below the threshold for meaningful clinical benefit in terms of objective response rate.

Michel Detheux, CEO of iTeos, emphasized the importance of sharing these data with the scientific community at an upcoming medical meeting, despite the disappointing outcomes.

Industry-Wide Challenges for TIGIT Therapies

The failure of belrestotug is not an isolated incident but part of a broader trend in the pharmaceutical industry. Several major players have recently abandoned their TIGIT programs:

• BeiGene halted development of ociperlimab for NSCLC in April 2025 after an independent data monitoring committee found the Phase III AdvanTIG-302 trial unlikely to meet its primary endpoint of overall survival.
• Roche discontinued tiragolumab in July 2024 following disappointing results from the Phase II/III SKYSCRAPER-06 trial in NSCLC.
• Merck ended a late-stage study of vibostolimab, combined with Keytruda, for melanoma treatment in May 2024.

These setbacks highlight the difficulties in developing effective therapies targeting the TIGIT pathway, which was once considered a promising approach to enhance cancer immunotherapy.

Financial and Strategic Implications

The discontinuation of belrestotug marks the end of a high-stakes collaboration between GSK and iTeos, initiated in 2021 with an upfront payment of $625 million and potential milestone payments of up to $1.45 billion.

In response to this setback, iTeos has announced immediate steps to preserve capital and has initiated a strategic review of its business. The company aims to identify opportunities to maximize value for shareholders in light of the current market conditions.

As the pharmaceutical industry reassesses the potential of TIGIT-targeted therapies, attention may shift to other approaches in cancer immunotherapy. However, some companies, such as Gilead and Arcus, continue to pursue TIGIT inhibitors, with Phase 3 results expected next year for their candidate in gastrointestinal cancer.