Arcus Biosciences and Gilead Sciences have decided to stop developing a domvanalimab combination for gastric and esophageal cancers after the treatment failed to improve overall survival in a Phase III trial. The companies made this decision following an interim analysis of the STAR-221 study, which found no difference in outcomes between patients receiving the domvanalimab-based regimen and those treated with Bristol Myers Squibb’s Opdivo plus chemotherapy.
“Patients in the domvanalimab-containing arm derived the same benefit as patients treated in the control arm, and there were no new safety concerns,” said Richard Markus, chief medical officer at Arcus.
The TIGIT-targeting therapy had previously attracted attention as a potential new approach in immuno-oncology, but recent clinical failures have cast doubt on its effectiveness. Truist Securities analysts stated: “Au Revoir TIGIT. This update makes us more pessimistic on the entire TIGIT program, and so we are conservatively closing the chapter on Dom.” Following this news, Arcus’ stock dropped 12 percent.
Mizuho Securities noted that investors did not expect much from the TIGIT therapy, describing the development as a “clearing event” for Arcus’ stock.
The discontinued studies include both STAR-221 and a Phase II trial called EDGE-Gastric. An independent data monitoring committee recommended ending these trials. Arcus and Gilead are working with investigators to determine next steps for affected patients and plan to release further analysis later.
“The results from STAR-221 are not what we had hoped for, and we have important work ahead to meet the needs of patients on our domvanalimab studies and also accelerate the casdatifan and I&I programs,” said Terry Rosen, CEO of Arcus.
Arcus will now focus primarily on casdatifan—a HIF-2a inhibitor being developed for kidney cancer—and its early-stage inflammation and immunology pipeline. Casdatifan has shown efficacy in an early-stage study involving late-line clear cell renal cell carcinoma patients. The company expects multiple updates from this program in 2026 and aims to begin a Phase III trial by year-end 2026.
Analysts from Truist anticipate that Arcus may further reduce its pipeline next year to concentrate resources on casdatifan and related programs. Mizuho described casdatifan as having $2 billion peak revenue potential, highlighting that it is wholly owned by Arcus with no profit-sharing obligations.
Arcus reports holding $1 billion in cash and investments, which should fund operations into the second half of 2028.
TIGIT therapies have faced setbacks across several companies recently. For example, GSK ended its partnership with iTeos Therapeutics after their joint drug belrestotug failed in a Phase II trial earlier this year—an outcome that led to iTeos shutting down operations. Other pharmaceutical companies like Roche and Merck have also experienced unsuccessful results with their own TIGIT programs.
