Arcus and Gilead Discontinue TIGIT Therapy After Phase III Gastric Cancer Trial Failure
核心洞察
Arcus and Gilead discontinued development of domvanalimab combination therapy in gastric and esophageal cancers after the Phase III STAR-221 trial failed to improve overall survival compared to Bristol Myers Squibb (搜索)'s Opdivo plus chemotherapy.
The failure represents another significant setback for the TIGIT (搜索) class of immunotherapies, following similar failures from Roche, GSK, and Merck (搜索), leaving AstraZeneca as the primary remaining player in this therapeutic area.
Arcus is pivoting to focus on casdatifan, a HIF-2α (搜索) inhibitor for kidney cancer (搜索), which analysts view as having multi-billion-dollar revenue potential and is wholly owned by the company.
Arcus Biosciences and partner Gilead Sciences have discontinued development of their anti-TIGIT (搜索) antibody domvanalimab in gastric and esophageal cancers following a futility analysis in the Phase III STAR-221 trial. The decision marks another significant failure for the TIGIT class of immunotherapies and prompted Arcus to shift its primary focus to casdatifan, a HIF-2α (搜索) inhibitor for kidney cancer (搜索).
Trial Results and Discontinuation
The STAR-221 trial tested domvanalimab combined with Arcus' PD-1 (搜索) monoclonal antibody zimberelimab and chemotherapy against Bristol Myers Squibb (搜索)'s Opdivo plus chemotherapy in patients with first-line advanced gastric and esophageal cancers. An independent data monitoring committee recommended discontinuation after an interim analysis showed no improvement in overall survival compared to the control arm.
"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, Arcus' chief medical officer. The companies will also discontinue the Phase II EDGE-Gastric trial based on the committee's recommendation.
TIGIT Class Struggles Continue
The failure adds to a growing list of setbacks for TIGIT (搜索)-targeted therapies across the pharmaceutical industry. Roche terminated its tiragolumab program after the pivotal Skyscraper-14 trial failed in liver cancer (搜索) in July. GSK walked away from its partnership with iTeos Therapeutics after their drug belrestotug failed to improve progression-free survival in a Phase II trial, ultimately leading to iTeos' closure in May. Merck (搜索)'s vibostolimab has also encountered failures.
These developments leave AstraZeneca as the primary remaining company with significant TIGIT (搜索) presence, developing rilvegostomig, a bispecific antibody that targets both TIGIT and PD-1 (搜索) with reduced Fc effector function. The drug is currently in 11 pivotal studies.
Strategic Pivot to Casdatifan
Following the STAR-221 results, Arcus CEO Terry Rosen announced the company would accelerate development of casdatifan and its inflammation and immunology programs. "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," Rosen stated.
Casdatifan has already demonstrated efficacy activity in the Phase I/Ib ARC-20 trial for patients with late-line clear cell renal cell carcinoma (搜索). The company expects multiple readouts for the program in 2026 and is targeting Phase III trial initiation by the end of that year.
Financial Impact and Market Response
Arcus shares declined 12% to $21.91 following the announcement. Truist Securities wrote off the entire domvanalimab program, stating "Au Revoir TIGIT (搜索). This update makes us more pessimistic on the entire TIGIT program, and so we are conservatively closing the chapter on Dom."
However, analysts remain optimistic about casdatifan's potential. Mizuho Securities called it "fundamentally a good asset" with $2 billion in peak revenue potential, while Truist analysts described it as "a potential multi-billion-dollar opportunity." The drug's wholly-owned status by Arcus means no profit sharing, unlike the Gilead partnership arrangement for domvanalimab.
Remaining Domvanalimab Studies
Despite the gastric cancer (搜索) failure, domvanalimab continues in two other Phase III trials in lung cancer (搜索). STAR-121 tests the combination with zimberelimab plus chemotherapy versus Keytruda plus chemotherapy in first-line metastatic NSCLC (搜索), while Pacific-8 evaluates domvanalimab on top of AstraZeneca's Imfinzi in stage III NSCLC.
However, industry observers note concerning parallels with previous TIGIT (搜索) failures, as similar lung cancer (搜索) trials with other TIGIT antibodies have also failed, including Roche's Skyscraper-03 and Merck (搜索)'s Keyvibe-007.
Arcus maintains strong financial positioning with $1 billion in cash and investments, expected to support company activities through the second half of 2028. The company is working with investigators to determine next steps for patients currently enrolled in the discontinued trials and plans to release a deeper analysis of the STAR-221 results at a later date.