Arcus and Summit Launch Casdatifan–Ivonescimab Trial in Metastatic Kidney Cancer

Arcus Biosciences and Summit Therapeutics have entered a clinical trial collaboration to evaluate the investigational combination of casdatifan and ivonescimab in clear cell renal cell carcinoma (ccRCC). The study will add a new cohort to the ongoing ARC-20 platform trial, with initial safety and preliminary efficacy data expected by mid-2027.

Arcus Biosciences and Summit Therapeutics have partnered to investigate a novel first-line treatment approach for metastatic clear cell renal cell carcinoma, the most common subtype of kidney cancer. The collaboration will evaluate Arcus’ investigational hypoxia-inducible factor 2-alpha (HIF-2α) inhibitor, casdatifan (AB521), in combination with Summit’s investigational PD-1/VEGF bispecific antibody, ivonescimab, through a new cohort in the ongoing ARC-20 platform study. Arcus will sponsor and conduct the study, while Summit will supply ivonescimab. Both companies will share study costs and retain commercial rights to their respective therapies. Initial safety and preliminary efficacy data are expected by mid-2027.

Scientific Rationale for the Combination

Clear cell renal cell carcinoma frequently develops through dysregulation of the HIF-2α pathway, making HIF-2α inhibition an established therapeutic target. Casdatifan is an oral, once-daily small-molecule HIF-2α inhibitor that has shown encouraging activity in early clinical studies, including high response rates and low primary disease progression, supporting advancement into late-stage development. Its safety profile also supports evaluation in combination regimens.

Ivonescimab is a tetravalent bispecific antibody that simultaneously blocks programmed cell death protein-1 (PD-1) and vascular endothelial growth factor (VEGF), two pathways that contribute to tumor growth, immune suppression, and angiogenesis in renal cell carcinoma. More than 4,000 patients have received ivonescimab in clinical studies globally, while over 70,000 patients have been treated in routine clinical practice in China. The therapy is currently being evaluated in multiple Phase 3 oncology trials across several tumor types.

Trial Expands the ARC-20 Platform Study

The new cohort will become part of ARC-20, Arcus’ multi-cohort platform study investigating casdatifan as monotherapy and in combination with multiple treatment strategies across metastatic ccRCC. The study spans first-line, second-line, and later-line disease settings.

In addition to the planned ivonescimab cohort, ARC-20 is evaluating casdatifan with the PD-1 inhibitor zimberelimab, a triple combination of casdatifan, zimberelimab, and ipilimumab, and casdatifan plus cabozantinib in immunotherapy-experienced patients. Additional late-line development includes a planned cohort evaluating casdatifan with tivozanib in patients previously treated with another HIF-2α inhibitor.

Arcus is also enrolling patients in the global Phase 3 PEAK-1 trial comparing casdatifan plus cabozantinib with cabozantinib alone in immunotherapy-experienced metastatic ccRCC. The company expects to complete enrollment in PEAK-1 and initiate another Phase 3 study in the first-line metastatic setting before the end of 2026.

Addressing an Ongoing Need in Advanced Kidney Cancer

According to the American Cancer Society, an estimated 80,450 people in the United States will be diagnosed with kidney cancer in 2026. While localized disease carries a favorable prognosis, the five-year survival rate falls to approximately 19% once cancer becomes metastatic, highlighting the continued need for more effective first-line therapies.

Company executives said the collaboration combines complementary mechanisms by pairing HIF-2α inhibition with dual PD-1 and VEGF blockade. The regimen is being explored as a potential tyrosine kinase inhibitor (TKI)-sparing strategy that could differentiate it from current first-line standards, which typically combine immune checkpoint inhibitors with VEGF-targeting TKIs such as pembrolizumab plus axitinib. If clinical development is successful, the combination could provide an alternative treatment approach for patients with advanced ccRCC.

Regulatory Path

Both casdatifan and ivonescimab remain investigational for clear cell renal cell carcinoma, and neither therapy has received regulatory approval for this indication. The new ARC-20 cohort will help determine whether the combination’s scientific rationale translates into meaningful clinical benefit and will inform future late-stage development in metastatic kidney cancer.

Reference

Arcus Biosciences – Arcus Biosciences and Summit Therapeutics Enter Into Clinical Trial Collaboration to Evaluate Casdatifan Combined with Ivonescimab in Kidney Cancer