Gilead and Arcus Bioscience’s monoclonal antibody (mAb), domvanalimab, has produced positive results in a Phase II gastroesophageal adenocarcinoma trial, offering new hope to the struggling anti-TIGIT modality.
During the Phase II EDGE-Gastric study (NCT05329766), the Fc-silent anti-T cell immunoreceptor with immunoglobulin and ITIM domain (TIGIT) antibody was shown to bolster overall survival (OS) in the A1 arm of the study.
Results were outlined in an abstract debuted before the start of the 2025 European Medical Society of Oncology (ESMO) Congress, taking place between 17-21 October in Berlin, Germany.
This patient cohort, which was one of four trialling domvanalimab in the first-line setting, saw patients receive a combination of the mAb alongside programmed cell death protein-1 (PD-1) antibody, zimberelimab and chemotherapy.
Patients treated with this regimen demonstrated an OS of 26.7 months, with half of those enrolled onto the A1 arm living for more than two years.
The combination also demonstrated a median progression-free survival (PFS) of 12.9 months, while the patient objective response rate (ORR) to treatment was 59%.
Meanwhile, the drugs have been proven to be safe and tolerable thus far when used in tandem. Immune-related treatment-emergent adverse events (TEAEs) were observed in 22% of patients enrolled in the A1 arm.
To further explore the potential of its investigational mAbs in gastroesophageal cancer, Gilead and Arcus are currently conducting the Phase III STAR-221 study (NCT05568095), which is set for primary completion at the end of 2026.
Reviving interest in anti-TIGITs
While the results from the EDGE-Gastric study thus far have been positive, this has not always been the case for anti-TIGIT therapies, which have traditionally flunked late-stage trials due to a lack of efficacy.
A high-profile case was Roche’s tiragolumab, which the Swiss pharma dropped in November 2024 after it failed to significantly improve outcomes in a Phase III lung cancer trial.
It was a similar story for GSK and iTeos’ belrestotug, which the pair scrapped after the disappointing results of two mid-stage lung cancer trials – despite positive sentiments at last year’s ESMO Congress.
MSD’s vibostolimab also failed to make it over the regulatory line, as the German pharma discontinued a Phase III trial exploring the drug alongside blockbuster checkpoint inhibitor Keytruda (pembrolizumab) due to a pre-planned analysis suggesting that the OS endpoint would not be met.
Most recently, BeOne Medicines’ ociperlimab got the boot, with poor predictions for OS outcomes in a Phase III non-small cell lung cancer (NSCLC) trial making it the fourth anti-TIGIT to be discontinued within the last year.
According to Arcus’ CMO, Richard Markus, domvanalimab may have shown success in the clinic due to the drug’s Fc-silent nature, which he noted could “provide differentiated efficacy and safety,” compared with previous anti-TIGIT therapies.
If domvanalimab were to obtain approval in this indication, a patient-based forecast from analysts at GlobalData suggests that the drug could near blockbuster status in 2032, making an estimated $974m for Arcus and Gilead.
