Arcus concentrates its R&D investment on Casdatifan and Emerging Inflammation and Immunology Portfolio after discontinuation of STAR-221 study with domvanalimab-based combination in upper gastrointestinal cancers

The Phase 3 STAR-221 study evaluating a domvanalimab-based combination in upper gastrointestinal cancers, being conducted in partnership with Gilead Sciences, Inc., will be discontinued due to futility. The decision is based on the recommendation from the Independent Data Monitoring Committee (IDMC) following its review of data from an event-driven, pre-specified interim analysis of overall survival (OS).

STAR-221 evaluated the anti-TIGIT antibody domvanalimab plus anti-PD-1 antibody zimberelimab and chemotherapy versus nivolumab plus chemotherapy as a first-line treatment for advanced gastric and esophageal cancers. At the interim analysis, the domvanalimab-based combination did not improve OS relative to that of nivolumab plus chemotherapy. The safety profile for the domvanalimab-based combination was similar to that of nivolumab plus chemotherapy, and there were no new safety findings identified.

Arcus’s R&D investment and resources will focus on casdatifan, a potential best-in-class HIF-2a inhibitor with robust single-agent activity, and multiple data readouts are expected in 2026, and its emerging small molecule I&I programs (five programs targeting inflammatory and autoimmune (I&I) diseases; a small molecule targeting MRGPRX2 is expected to enter the clinic in 2026)

With approximately $1B of cash and investments Arcus expects to be able to fund its planned operations until at least the second half of 2028.

Casdatifan targets a validated mechanism of action and has shown robust single-agent activity based on data reported from more than 120 patients with late-line clear cell renal cell carcinoma (ccRCC) in the ARC-20 Phase 1/1b clinical study. Those data have shown improvement on every efficacy measure evaluated, including overall response rate and progression-free survival (PFS), relative to reported data for the only marketed HIF-2a inhibitor. Arcus owns all of the rights to casdatifan outside of Japan and certain other Asian territories, which were optioned by Taiho Pharmaceutical Co., Ltd. in October 2025.

Arcus is focused on rapidly developing casdatifan in both immunotherapy (IO)-experienced and first-line metastatic ccRCC, and its clinical investment in 2026 and 2027 will be primarily focused on maximizing the potential of casdatifan. The casdatifan program is expected to have multiple data readouts and cohort and study initiations in 2026 including:

• Early 2026: Additional analyses from the ARC-20 cohorts evaluating casdatifan monotherapy in late-line ccRCC, including updated PFS data for the 100mg once-daily (QD) cohort, which utilizes the selected Phase 3 dose and formulation.
• Mid-2026: More mature data from the ARC-20 cohort evaluating casdatifan plus cabozantinib in the IO-experienced setting. This is the same setting and combination being evaluated in the ongoing Phase 3 PEAK-1 study.
• 2H 2026: Initial data from one or more ARC-20 cohorts evaluating casdatifan in early-line settings, as well as a go-no-go decision on the Phase 3 portion of eVOLVE-RCC02.
• Late 2026: Potential initiation of a Phase 3 registrational study in an early-line or first-line ccRCC setting.

Arcus's oncology portfolio also includes quemliclustat, a small-molecule CD73 inhibitor that completed enrollment of PRISM-1, the Phase 3 study in pancreatic cancer, earlier this year. Results are expected in 2027 for the registrational study, which is evaluating quemliclustat plus gemcitabine/nab-paclitaxel versus gemcitabine/nab-paclitaxel in first-line metastatic pancreatic ductal adenocarcinoma.

Arcus’s I&I portfolio includes several oral, small molecules being developed in indications currently dominated by injectable drugs. The portfolio includes the following programs: MRGPRX2, TNF, CCR6, CD89 and CD40L. Arcus expects to advance two potentially best-in-class small molecule inhibitors into the clinic in the timeframes noted below:

• 2026: MRGPRX2, a potential treatment for atopic dermatitis and chronic spontaneous urticaria; and
• Late 2026 - early 2027: TNF, a potential treatment for rheumatoid arthritis, psoriasis and inflammatory bowel disease (such as ulcerative colitis).

Domvanalimab, zimberelimab and quemliclustat are investigational molecules, and neither Arcus nor Gilead has received approval from any regulatory authority for any use globally, and their safety and efficacy have not been established.

Casdatifan is also an investigational molecule, and Arcus has not received approval from any regulatory authority for any use globally, and its safety and efficacy have not been established.