GSK
Pharmaceutical R&D Manufacturer
'%20fill='%23FFFFFF'%3E%3Crect%20x='249'%20y='126'%20width='1'%20height='1'%3E%3C/rect%3E%3C/g%3E%3C/g%3E%3C/svg%3E)
On May 13, 2025, according to foreign media reports, GlaxoSmithKline (GSK) recently decided to terminate the anti-TIGIT antibody belrestotug (EOS-448) project, which was being co-developed with iTeos Therapeutics. Although the drug showed positive efficacy in a Phase II clinical trial in 2024, the latest interim survival data did not meet expectations, prompting GSK to withdraw. Affected by this, iTeos' stock price plummeted, and the company announced layoffs to cut costs.
This incident is the latest epitome of the R&D difficulties surrounding the TIGIT target. In recent years, global pharmaceutical companies such as Roche, Merck, and BeiGene have successively stumbled in the TIGIT field, with cumulative R&D investments exceeding 20 billion USD now facing the risk of being "washed away."
Four years ago, GSK acquired the rights to belrestotug with an upfront payment of $625 million. At that time, TIGIT (T-cell immunoglobulin and ITIM domain), as a popular target in the field of immunotherapy, attracted the attention of many pharmaceutical companies.
Bristol-Myers Squibb, Gilead Sciences, Merck & Co., and Roche are all actively developing related drugs in an effort to bring the benefits of immunotherapy to more cancer patients. However, despite early studies showing some signs of efficacy, these drugs have failed to meet expectations in terms of improving patient survival rates.
GSK and iTeos’ decision to terminate the belrestotug project is based on an evaluation of its Phase 2 clinical trial data. One of the studies was testing belrestotug in combination with the anti-PD-1 checkpoint inhibitor Jemperli in untreated, unresectable, locally advanced or metastatic PD-L1 high-expressing non-small cell lung cancer (NSCLC) patients. While the combination therapy showed improvement in the primary endpoint of objective response rate, the results for progression-free survival did not reach a level that the developers considered clinically meaningful.
An interim analysis of another Phase 2 clinical trial for PD-L1 positive head and neck squamous cell carcinoma also showed that the response rate trend in the belrestotug combination therapy group was below a meaningful threshold compared to the Jemperli monotherapy group. Based on these data, GSK and iTeos have decided to terminate the belrestotug program and their collaboration, and all trial groups containing belrestotug will be concluded. Additionally, GSK has halted enrollment in the Phase 3 trial group testing belrestotug in combination with Jemperli as a first-line treatment for locally advanced or metastatic PD-1 selective NSCLC.
This setback has forced iTeos to immediately take measures to conserve cash and begin evaluating strategic options. As of the end of March this year, iTeos had $624.3 million in cash, which, under the previous spending plan, could support the company’s operations until 2027. In addition to the belrestotug project, iTeos is also developing an ENT1 inhibitor and an anti-TREM2 antibody, both of which are currently in Phase 1 cancer research.
In the field of tumor immunotherapy, the TIGIT (T-cell immunoglobulin and ITIM domain) target was once regarded as another significant breakthrough following PD-1/PD-L1. However, in recent years, several pharmaceutical companies, including BeiGene, Roche, and Merck, have encountered consecutive setbacks in the development of TIGIT antibodies, sparking in-depth discussions within the industry about the challenges of TIGIT target research and development.
On April 3, 2025, BeiGene announced the termination of the clinical development program for its anti-TIGIT antibody ociperlimab. This decision was based on the futility analysis results from the Independent Data Monitoring Committee (IDMC) of the Phase 3 AdvanTIG-302 trial. The trial aimed to evaluate the efficacy of ociperlimab in combination with tislelizumab (an anti-PD-1 antibody) for the first-line treatment of patients with locally advanced, unresectable, or metastatic non-small cell lung cancer (NSCLC) who have high PD-L1 expression and no sensitizing EGFR mutations or ALK translocations. (Related report:《BeiGene Terminates Development of TIGIT Antibody, Roche and Merck Suffer Consecutive Setbacks...》）
The overall efficacy and safety data assessment of the trial indicates that the study may not achieve the primary endpoint of overall survival (OS). Despite no new safety signals being identified, this outcome implies that BeiGene's substantial investment in this project (which had accumulated to 2.09 billion yuan by the end of the first half of 2024) may not yield the expected returns.
Roche's TIGIT monoclonal antibody tiragolumab has encountered consecutive setbacks in two major indications: extensive-stage small cell lung cancer (ES-SCLC) and non-small cell lung cancer (NSCLC). In March 2022, Roche announced that the Phase III clinical trial SKYSCRAPER-02, which evaluated tiragolumab in combination with atezolizumab as a first-line treatment for extensive-stage small cell lung cancer (ES-SCLC), did not meet the primary endpoint of progression-free survival (PFS). Two months later, Roche delivered more bad news: the Phase III SKYSCRAPER-01 study data evaluating tiragolumab in combination with atezolizumab for first-line treatment of PD-L1 high-expression NSCLC failed to reach the co-primary endpoint of PFS.
Merck was no exception, as its TIGIT antibody vibostolimab performed poorly in multiple clinical trials. In March 2023, Merck announced that the non-pivotal Phase 2 clinical study KeyVibe-002 of MK-7684A for the treatment of metastatic NSCLC did not meet the primary endpoint of PFS, and its efficacy was inferior to docetaxel; based onMultiple setbacks in TIGIT antibody development; in December 2024, Merck officially announced the termination of the vibostolimab development plan.
Despite the numerous challenges in the development of the TIGIT target, it does not mean complete failure. Some pharmaceutical companies are still exploring the potential of TIGIT-targeted drugs. For instance, Gilead and Arcus Biosciences are advancing domvanalimab into late-stage trials, including studies in NSCLC; AstraZeneca is also progressing its TIGITxPD-1 bispecific antibody rilvegostomig through a series of Phase 3 studies.