Arcus Biosciences to Test Casdatifan and Volrustomig Combo in Renal Cell Carcinoma Trial

Arcus Biosciences, a biopharmaceutical company focused on cancer treatment, has entered a clinical trial collaboration with AstraZeneca. This partnership aims to explore the combined use of Arcus’s investigational HIF-2a inhibitor, casdatifan (AB521), with AstraZeneca’s investigational PD-1/CTLA-4 bispecific antibody, volrustomig, in treating patients with clear cell renal cell carcinoma (ccRCC).

Casdatifan has demonstrated promising potential based on its pharmacokinetic and pharmacodynamic profiles, as well as emerging clinical data from the ARC-20 study involving ccRCC patients. Terry Rosen, Ph.D., CEO of Arcus, expressed optimism about the collaboration, stating that it could significantly improve outcomes for ccRCC patients through the innovative combination of casdatifan and volrustomig.

Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer at AstraZeneca, highlighted the efficacy of volrustomig monotherapy in first-line advanced ccRCC. He emphasized the potential benefits of combining HIF-2a inhibition with volrustomig to achieve deeper and more durable responses in patients.

Under this collaboration, AstraZeneca will sponsor and manage a study to evaluate the safety and early efficacy of the casdatifan and volrustomig combination in advanced ccRCC patients. This marks the second clinical collaboration between Arcus and AstraZeneca, following their 2020 partnership for the PACIFIC-8 study. This earlier study involved a Phase 3 trial of domvanalimab, an anti-TIGIT antibody, in combination with durvalumab, an anti-PD-L1 antibody, for patients with unresectable Stage III non-small cell lung cancer.

In addition, under a separate agreement, Gilead has the option to co-develop and commercialize casdatifan based on certain data milestones provided by Arcus.

Casdatifan is a small-molecule inhibitor targeting HIF-2a, a transcription factor crucial for oxygen sensing in various organs and tumors. In ccRCC, HIF-2a dysregulation often results from genetic abnormalities in the VHL pathway, causing pseudohypoxia and increased expression of proteins linked to cancer cell proliferation, survival, treatment resistance, and angiogenesis. Casdatifan is currently being tested in ARC-20, a Phase 1/1b study, and STELLAR-009, a Phase 1b/2 study, both of which involve cancer patients, including those with advanced solid tumors like ccRCC.

Both casdatifan and domvanalimab are still investigational, with no global regulatory approval for any use, meaning their safety and efficacy have yet to be established.

According to the American Cancer Society, kidney cancer ranks among the top 10 most common cancers in the U.S., with an estimated 81,600 new cases expected in 2024. Clear cell RCC is the most prevalent form of kidney cancer among adults. While early-stage detection of RCC has a high five-year survival rate, the prognosis for advanced or late-stage metastatic RCC is much poorer, with a five-year survival rate of only 15%. In 2022, approximately 32,200 patients with advanced kidney cancer in the U.S. required systemic therapy, with over 20,000 receiving first-line treatment.

Arcus Biosciences, founded in 2015, is dedicated to developing innovative cancer therapies, including new combination treatments targeting various biological pathways such as TIGIT, PD-1, HIF-2a, and others. The company collaborates with industry partners, patients, and physicians globally to advance its clinical and preclinical programs aimed at improving cancer treatment outcomes.