GSK and iTeos Therapeutics announced Tuesday they are discontinuing development of belrestotug, their experimental TIGIT-targeting cancer immunotherapy, after the drug failed to meet efficacy criteria in a Phase 2 clinical trial. The decision marks another significant setback for the once-promising TIGIT pathway in cancer treatment.
The two-drug regimen combining belrestotug with GSK's PD-1 inhibitor Jemperli (dostarlimab) did not significantly improve progression-free survival compared to Jemperli alone in patients with non-small cell lung cancer. Additionally, the companies reported that study arms including patients with head and neck cancer showed a "trend below the meaningful threshold" for drug responses.
Clinical Trial Results Lead to Program Termination
Based on these disappointing results, GSK and iTeos are halting all ongoing clinical trials of belrestotug, including an active Phase 3 study in lung cancer. The decision effectively ends the collaboration agreement the companies formed four years ago, when GSK paid iTeos $625 million upfront for rights to the drug, with potential additional payments of up to $1.45 billion.
"Given the current market conditions, we are taking immediate steps to preserve capital and have initiated a strategic review," said Michel Detheux, CEO of iTeos Therapeutics, in a statement. The termination eliminates iTeos' most advanced drug candidate and the future milestone payments it could have received from GSK.
TIGIT's Troubled Path in Cancer Immunotherapy
TIGIT (T cell immunoreceptor with Ig and ITIM domains) emerged as a highly pursued target in cancer immunotherapy over the past decade. The protein is believed to suppress immune responses against cancer, and pharmaceutical companies hypothesized that blocking it could enhance the efficacy of established checkpoint inhibitors like PD-1 blockers.
This scientific rationale sparked substantial investment across the industry. Major pharmaceutical companies including Roche, Merck & Co., Bristol Myers Squibb, and Gilead Sciences all developed or acquired TIGIT-targeting candidates. When GSK partnered with iTeos in 2021, the company expressed optimism that combinations involving belrestotug could become "transformative medicines" for many cancer patients.
However, the TIGIT hypothesis has faced mounting challenges as multiple clinical trials have failed to demonstrate meaningful clinical benefits. Several companies have already terminated their TIGIT research programs following disappointing results.
Previous Encouraging Data Not Sustained
The decision to end belrestotug development comes despite initially promising results. Last year, iTeos and GSK reported that the combination of belrestotug and Jemperli shrank tumors in approximately twice as many people as Jemperli alone in their Phase 2 lung cancer study, meeting the trial's primary objective for objective response rate.
However, this tumor shrinkage did not translate into the more clinically meaningful endpoint of delaying disease progression, which was a secondary study goal but considered essential for continued development.
Impact on iTeos and Future Directions
For iTeos, the failure represents a significant blow to its pipeline and financial outlook. The company must now pivot to earlier-stage assets while conducting a strategic review to maximize shareholder value.
The setback also raises broader questions about the future of TIGIT as a therapeutic target. While some companies continue to pursue TIGIT inhibitors with optimized properties or novel combinations, the growing list of clinical disappointments has dampened enthusiasm for what was once considered one of the most promising pathways in immuno-oncology.
Industry analysts will be closely watching the remaining TIGIT programs in development to determine whether specific patient populations or combination approaches might still benefit from targeting this pathway, or if resources should be redirected toward more promising immunotherapy targets.
