Arcus Biosciences and AstraZeneca have entered into a clinical trial collaboration agreement to investigate a novel combination therapy for clear cell renal cell carcinoma (ccRCC). The collaboration will evaluate Arcus's investigational HIF-2a inhibitor, casdatifan (AB521), in conjunction with AstraZeneca's investigational PD-1/CTLA-4 bispecific antibody, volrustomig, in patients with ccRCC. This partnership aims to address the unmet need for more effective treatments for this common type of kidney cancer.
AstraZeneca will sponsor and operationalize the clinical trial to assess the safety and early efficacy of the casdatifan plus volrustomig combination in patients with advanced ccRCC. The study will explore whether the combination can improve patient outcomes by leveraging the distinct mechanisms of action of the two investigational agents.
Rationale for the Combination
Clear cell RCC is characterized by dysregulation of HIF-2a due to genetic abnormalities in the VHL pathway, leading to increased expression of proteins involved in cancer cell proliferation, survival, treatment resistance, and angiogenesis. Casdatifan is designed to inhibit HIF-2a, potentially disrupting these processes. Volrustomig, as a bispecific antibody targeting PD-1 and CTLA-4, aims to enhance the anti-tumor immune response. Combining these agents could provide a synergistic effect, leading to deeper and more durable responses in patients with ccRCC.
"We believe casdatifan has best-in-class potential, based on the observed PK and PD profiles and the emerging clinical data from our ARC-20 study in patients with ccRCC," said Terry Rosen, Ph.D., chief executive officer of Arcus. "This agreement will enable Arcus and AstraZeneca to collaborate and assess the potential for the novel combination of casdatifan with volrustomig to improve outcomes for patients with ccRCC."
Cristian Massacesi, chief medical officer and oncology chief development officer at AstraZeneca, added, "Renal cell carcinoma is a known CTLA-4-responsive tumor type, and our first-in-human study with volrustomig monotherapy demonstrated encouraging efficacy in first-line advanced ccRCC. We are excited by the potential to build on this by combining HIF-2a inhibition with volrustomig to drive deeper and more durable responses for patients."
Previous Collaborations and Ongoing Studies
This collaboration marks the second between Arcus and AstraZeneca. In 2020, the companies announced a clinical collaboration for PACIFIC-8, a registrational Phase 3 study of domvanalimab, an Fc-silent anti-TIGIT antibody, added to backbone global standard-of-care durvalumab, an anti-PD-L1 antibody, in patients with unresectable Stage III non-small cell lung cancer.
Arcus is also evaluating casdatifan in the Phase 1/1b ARC-20 study in cancer patients and the Phase 1b/2 STELLAR-009 study in combination with zanzalintinib in patients with advanced solid tumors, including ccRCC. Furthermore, Arcus recently completed enrollment in the Phase III STAR-221 trial of domvanalimab and zimberelimab plus chemotherapy in patients with locally advanced unresectable or metastatic gastric, gastroesophageal junction, or esophageal adenocarcinoma (upper GI cancers).
Market and Disease Context
Kidney cancer is among the top 10 most commonly diagnosed forms of cancer in the U.S., with an estimated 81,600 Americans expected to be diagnosed in 2024, according to the American Cancer Society. Clear cell RCC is the most prevalent type of kidney cancer in adults. While early-stage RCC has a high five-year survival rate, the rate drops to approximately 15% for patients with advanced or late-stage metastatic disease. In 2022, about 32,200 patients with advanced kidney cancer in the U.S. required systemic therapy, with over 20,000 receiving first-line treatment, highlighting the significant need for improved therapeutic options.
