Gilead and Arcus Report Promising Results for Anti-TIGIT Antibody in Gastric Cancer Study

Gilead Sciences and Arcus Biosciences have unveiled encouraging overall survival (OS) data for their anti-TIGIT antibody domvanalimab, breathing new life into a therapeutic approach that has faced setbacks in recent years. The phase 2b study results, focusing on patients with advanced gastric, gastroesophageal junction, or esophageal adenocarcinoma, have reignited interest in the TIGIT pathway as a potential target for cancer immunotherapy.

Domvanalimab Shows Impressive Survival Benefit

In the latest data release, Gilead and Arcus reported a median overall survival of 26.7 months for patients in arm A1 of their phase 2b study. This cohort, comprising 41 patients, received a combination of domvanalimab (1600 mg) and zimberelimab (480 mg), an investigational anti-PD-1 antibody, administered intravenously every four weeks alongside chemotherapy.

Dr. Sun Young Rha, director of the Songdang Institute for Cancer Research in Korea, described these OS data as "well beyond what would be required to demonstrate clinically meaningful benefit over standard of care." The study also revealed a confirmed overall response rate of 59% and a median progression-free survival of 12.9 months, consistent with previous reports from the trial.

Fc-Silent Approach: A Potential Differentiator

Domvanalimab stands out among TIGIT-targeting therapies due to its Fc-silent design. Unlike Fc-enabled antibodies that retain a fully functional Fc region, domvanalimab's Fc function has been mutated out. This approach may provide a crucial advantage, as many Fc-enabled TIGIT candidates from major pharmaceutical companies have faced clinical failures in recent years.

Dr. Richard Markus, Arcus' chief medical officer, emphasized the potential of this approach, stating, "These survival results add to the totality of data for domvanalimab and the role of anti-TIGIT-based combinations for the treatment of different cancers and reinforce our conviction that an Fc-silent anti-TIGIT antibody may provide differentiated efficacy and safety."

Looking Ahead: Ongoing Phase 3 Trial

The promising phase 2b results have bolstered confidence in the ongoing phase 3 study of domvanalimab and zimberelimab. This larger trial, involving 1,050 participants with the same range of cancers as the phase 2 study, will provide more comprehensive data on the efficacy and safety of this combination therapy.

As one of the few remaining TIGIT candidates in active development, alongside AstraZeneca's Fc-silent TIGIT/PD-1 bispecific antibody rilvegostomig, domvanalimab's progress is being closely watched by the oncology community. The outcome of these trials could potentially reshape the landscape of cancer immunotherapy and offer new hope for patients with difficult-to-treat gastrointestinal cancers.