The Phase 3 failure has prompted Gilead Sciences and Arcus Biosciences to terminate a mid-stage study of their TIGIT asset in lung cancer.
Gilead Sciences and Arcus Biosciences are discontinuing a late-stage study of their investigational TIGIT drug domvanalimab “due to futility,” prompting Gilead to start rolling back its years-long cancer collaboration with Arcus.
The trial, STAR-121, was testing domvanalimab in combination with a PD-1 blocker and chemotherapy for metastatic non-small cell lung cancer (NSCLC). Arcus didn’t provide specific data from the study in the legal filing, noting only that an independent data panel found the comparison against Merck’s Keytruda plus chemotherapy to be futile.
No new safety issues were found during regular check-ins with the data board, though the latest futility analysis did not include a safety assessment.
Arcus made the disclosure in a securities filing dated April 20, noting that Gilead has decided not to make an option continuation payment, a decision that will cut off the pharma’s access to a clutch of early-stage TIGIT therapies. Gilead’s opportunity to participate in the development of new Arcus early-stage programs will officially end on July 14.
Gilead, however, will retain its “existing time-limited options” to certain programs, including the small-molecule AXL blocker AB801, the anti-CD39 antibody AB598 and the MRGPRX2 antagonist AB102. The document doesn’t outline when these options are set to expire.
Aside from triggering Gilead’s pullback, STAR-121’s failure has pushed the partners to end the Phase 2 EDGE-Lung study of domvanalimab in NSCLC.
Gilead and Arcus linked up in May 2020 to work on next-generation cancer therapies, an effort that involved TIGIT programs. Initially, the partners saw some success as other TIGIT players struggled. In June 2024, for instance, long-term data from the Phase 2 EDGE-Gastric study showed a 58.5% overall response rate in patients with upper gastrointestinal cancers after treatment with domvanalimab plus an anti-PD-1 therapy.
Meanwhile, other players in the TIGIT arena were stumbling. A month after the EDGE-Gastric readout, Roche discontinued a Phase 2/3 lung cancer study after its TIGIT therapy tiragolumab, combined with Tecentriq, failed to significantly improve survival when compared to Keytruda plus chemotherapy. Merck itself ran into some TIGIT hardships and, in May 2024, terminated a late-stage study of its TIGIT candidate vibostolimab, which it was studying in combination with Keytruda for melanoma.
Last year, GSK and partner iTeos Therapeutics abandoned their TIGIT therapy belrestotug after a disappointing midstage readout.
The class’s troubles ultimately caught up to Gilead and Arcus. In December last year, a domvanalimab regimen flopped in a late-stage study of gastric and esophageal cancer, forcing the partners to abandon their plans in the indication.
The TIGIT tale has been rife not just with clinical failures but also with sunk upfront costs. As per a BioSpace analysis, companies have paid at least $1.4 billion upfront in partnership contracts centered on TIGIT drugs, almost all of which did not pay off. Milestones, which could potentially hit $5 billion in value, largely remain unpaid.
