Gilead, Arcus’ Anti-TIGIT Combinations Show Survival Advantage Over Anti-PD1 Monotherapy In Phase 2 Trial

Gilead Sciences and Arcus Biosciences have been testing doublet and triplet combination therapies containing their anti-TIGIT monoclonal antibody domvanalimab against the anti-PD-1 zimberelimab in the frontline treatment of metastatic non-small cell lung cancer (NSCLC) with high levels of PD-L1 expression. 

Domvanalimab was combined with zimberelimab in the doublet arm. A third agent, an A2a/b adenosine receptor antagonist called etrumadenant was added to the combination to form the triplet arm. 

The latest results from the Phase 2 study called ARC-7 showed that the two combination therapy arms improved median progression-free survival (PFS) and six-month landmark PFS rates compared to zimberelimab monotherapy. 

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Cutting Progression Risk By 45%

Domvanalimab is an investigational antibody designed to bind to TIGIT, a protein receptor on immune cells that act as a brake on the immune response. Cancer cells exploit TIGIT to avoid detection by the immune system, which is similar to the “don’t eat me” signal a.k.a. PD-L1. On top of ARC-7, the antibody is currently undergoing four Phase 3 trials across lung and gastrointestinal cancers. 

At the time of data cutoff of ARC-7, doublet and triplet combination therapy-treated patients who were followed up for a median duration of approximately 12 months showed a 45% reduction in the risk of disease progression or death for the doublet and 35% for the triplet. 

The domvanalimab-containing study arms also showed clinically meaningful improvements in the objective response rate (ORR) compared to zimberelimab monotherapy. The ORR of the doublet and triplet was 41% and 40%, compared to 27% for the zimberelimab arm. 

While the triplet did not show an improvement over the doublet, Gilead said that it reinforces the results seen in the doublet arm, and the study will continue to monitor the results as the data matures. 

On the safety side, there were no unexpected safety signals observed across the three study arms. The domvanalimab-containing arm seemed to be well tolerated. Grade 3 or higher adverse events did occur in 58% of patients in the zimberelimab arm compared to 47% in the doublet and 52% in the triplet arm. Immune-related side effects included rash and itches of varying degrees of severity, which were generally controlled with topical corticosteroids. 

“It is particularly encouraging to see that combination treatments may offer potentially meaningful advances for people with non-small cell lung cancer based on the largest, prospectively randomized Phase 2 study of anti-TIGIT and anti-PD1 antibodies to date,” said Melissa L. Johnson, M.D., Director, Lung Cancer Research, Sarah Cannon Research Institute at Tennessee Oncology, and Lead Investigator for the ARC-7 study.

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Joy Lin

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