Domvanalimab

Arcus Biosciences said it would discontinue the Phase III STAR-221 trial after an interim analysis found no survival advantage for its experimental domvanalimab-based regimen in first-line patients with upper gastrointestinal (GI) tract cancers.The news, which marks the latest in a string of high-profile disappointments for the TIGIT class, sent Arcus shares sliding over 14% on Friday.Despite TIGIT setbacks from the likes of Roche, Merck & Co., GSK and BeOne Medicines over the last few years, Arcus and partner Gilead Science pressed ahead with their approach.In October, they shared encouraging overall survival (OS) data from the Phase II EDGE-Gastric study of domvanalimab plus the anti-PD-1 antibody zimberelimab and chemotherapy as first-line treatment in 41 patients with locally advanced unresectable or metastatic gastric cancer. The triplet was associated with median OS of 26.7 months in both the overall population and a subset of 29 patients with PD-L1 tumour area positivity of at least 1% (see – Spotlight On: Arcus, Gilead’s gastric cancer readout is tentative step toward TIGIT resurrection).Low expectationsSTAR-221 was testing the same combination against standard-of-care with Bristol Myers Squibb's Opdivo (nivolumab) plus chemotherapy in 1040 patients who have locally advanced unresectable or metastatic gastric, gastroesophageal junction and oesophageal adenocarcinoma."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, in a release Friday. The decision to drop the study followed a recommendation from the study's independent data monitoring committee citing futility. EDGE-Gastric will also be discontinued.However, the broader struggles with anti-TIGIT drugs had already led analysts to dial back their expectations, which were "very low" around domvanalimab's potential, according Wedbush's Robert Driscoll.R&D pivotArcus said it now plans to pivot its R&D efforts toward casdatifan, an oral HIF-2a inhibitor in development for clear cell renal cell carcinoma (ccRCC), as well as five small-molecule programmes targeting MRGPRX2, TNF, CCR6, CD89 and CD40L for inflammatory and autoimmune (I&I) diseases.At this year's American Society of Clinical Oncology (ASCO) meeting, Arcus unveiled the first combination data from the Phase I/Ib ARC-20 study, showing a 46% confirmed response rate for casdatifan plus Exelixis' Cabometyx (cabozantinib) in immunotherapy-experienced ccRCC, outperforming historical benchmarks for either agent alone.Arcus also plans to advance two oral I&I candidates into the clinic, with an MRGPRX2 inhibitor for atopic dermatitis and chronic spontaneous urticaria slated for 2026, followed by a TNF inhibitor for rheumatoid arthritis, psoriasis and inflammatory bowel disease in late 2026 to early 2027.CEO Terry Rosen said, "We are fortunate to be well capitalised and plan to focus our resources on casdatifan, including studying new early-line combinations in kidney cancer, broadening its development into new tumour types, and extending our capabilities beyond oncology." The company said it has about $1 billion in cash and investments to see it through to at least the second half of 2028.

iStock, tiero The loss of domvanalimab is the latest in a string of high-pro recorded across the biopharma world for the TIGIT modality, including from GSK, Merck and Roche. The TIGIT class has sustained another blow, with Arcus and Gilead discontinuing development of a domvanalimab combination in gastric and esophageal cancers after the drug failed to improve overall survival and the Phase III test was deemed futile. The miss—another in the long tale of TIGIT—spurred Truist Securities to write off the entire domvanalimab program entirely, despite the continuation of studies in other gastrointestinal cancers and lung cancer. “Au Revoir TIGIT,” the firm quipped on Friday after the news was announced. “This update makes us more pessimistic on the entire TIGIT program, and so we are conservatively closing the chapter on Dom.” Arcus’ shares declined 12% to $21.91 on Friday afternoon. Mizuho Securities said investors had not expected much from the TIGIT therapy, so the news represents a “clearing event” for the stock. The Phase III STAR-221 trial was testing domvanalimab, an anti-TIGIT antibody, with Arcus’ PD-1 monoclonal antibody zimberelimab and chemotherapy against Bristol Myers Squibb’s Opdivo plus chemotherapy in patients with first-line advanced gastric and esophageal cancers. At the interim analysis, Arcus observed no improvement in overall survival compared to the Opdivo 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,” Richard Markus, Arcus’ chief medical officer, said in a statement Friday. Immuno-oncology Four Therapies Hanging On in Troubled TIGIT Space TIGIT-targeting therapies have largely disappointed in recent months, with failed studies, terminated partnerships and shuttered businesses. Here are five biopharma players staying alive with differentiated candidates against the once promising immuno-oncology target. July 7, 2025 · 9 min read · Tristan Manalac Read More Therefore, Arcus and partner Gilead will discontinue the trial and a Phase II test called EDGE-Gastric based on a recommendation from an independent data monitoring committee. The companies are working with investigators to determine next steps for the patients in these trials. They will also release a deeper analysis at a later date. “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,” Arcus CEO Terry Rosen said in a statement. Casdatifan, a HIF-2a inhibitor under development for kidney cancer, will now be Arcus’ primary focus, as well as an early-stage inflammation and immunology pipeline. The company has already recorded efficacy activity in the Phase I/Ib ARC-20 trial of casdatifan for patients with late-line clear cell renal cell carcinoma. The company is expecting multiple readouts for the program in 2026 and is targeting a Phase III trial initiation by the end of that year. Domvanalimab remains in the pipeline for now, but Truist expects Arcus to trim its pipeline in the new year to fully shift to casdatifan and the I&I programs. “We continue to view casdatifan as a potential multi-billion-dollar opportunity,” the analysts wrote. Mizuho, meanwhile, called casdatifan “fundamentally a good asset,” with $2 billion in peak revenue potential. The drug is also wholly owned by Arcus, which means no profit sharing as would be the case if the Gilead program had succeeded. Arcus has plenty of money on hand, with $1 billion in cash and investments, which is expected to support the company’s activities through the second half of 2028, according to the release. “Today effectively tightens the RCUS story,” Mizuho wrote. The loss of domvanalimab is the latest in a string of high pro recorded across the biopharma world for the TIGIT modality. This year alone, GSK walked away from a partnership with iTeos Therapeutics after their partnered drug belrestotug failed to improve progression-free survival in a Phase II trial. The failure ultimately led to the demise of iTeos, which closed down in May . TIGIT—which stands for T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif domain—is a receptor with immunosuppressive effects. Given that TIGIT is overexpressed in many cancers, drug developers have been diligently trying to block it in an effort to boost the body’s antitumor activity. In addition to Gilead and GSK, efforts by Roche and Merck have also been unsuccessful. .responsive-container { display: flex; flex-wrap: wrap; border: 1px solid #ededed; font-family: Helvetica, Arial, Sans-Serif; padding: 20px 20px 10px 20px; } .column-left { flex: 1; max-width: 45%; padding: 20px 20px 10px 20px; } .column-right { flex: 2; padding: 20px 20px 10px 20px; } @media (max-width: 768px) { .column-left, .column-right { max-width: 100%; flex: 100%; padding: 10px 0; } } Subscribe to ClinicaSpace! Clinical trial results, research news, the latest in cancer, cell and gene therapy hbspt.forms.create({ region: "na1", portalId: "4413123", formId: "674f4dc0-7371-4190-86cc-e1afd00b08ea", onFormSubmitted: function($form, data) { window.dataLayer = window.dataLayer || []; window.dataLayer.push({ 'event': 'GTMevent', 'event_name': 'newsletter_sign_up' }); } });