Gilead Sciences, Inc. (Nasdaq: GILD) and Arcus Biosciences, Inc. (NYSE: RCUS) have released promising new data from their collaborative study, ARC-9, during an oral session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The Phase 1b/2 study assessed the efficacy of etrumadenant combined with zimberelimab, FOLFOX chemotherapy, and bevacizumab (EZFB) in treating third-line metastatic colorectal cancer (mCRC).

Encouraging Results in Colorectal Cancer Therapy

The study, named Cohort B of ARC-9, demonstrated that the EZFB regimen significantly reduced the risk of death in patients with mCRC who have progressed on at least two prior therapies. Dr. Zev A. Wainberg, M.D., MSc, Co-Director of the GI Oncology Program at the University of California Los Angeles and principal investigator of the ARC-9 trial, highlighted the regimen’s impact: “19.7 months is the longest median overall survival reported in third-line mCRC and warrants further investigation of an etrumadenant-based regimen as a potential treatment option in CRC1.”

Safety and Efficacy of the EZFB Regimen

The EZFB treatment regimen showed a safety profile consistent with the known safety profiles of each individual molecule, without unexpected toxicities. The regimen also reported lower rates of treatment emergent adverse events leading to discontinuation compared to those treated with regorafenib, a standard treatment for mCRC.

Mechanism and Potential of Etrumadenant and Zimberelimab

Etrumadenant is a dual A2a/A2b adenosine receptor antagonist that prevents adenosine-mediated immunosuppression in the tumor microenvironment, potentially restoring activation of antitumor immune cells and leading to tumor cell death. Zimberelimab, an anti-programmed cell death protein-1 (PD-1) monoclonal antibody, complements this by aiming to restore antitumor activity of T cells. Together, these agents represent a novel approach to overcoming the immunosuppressive barriers in mCRC treatment.

Global Impact and Future Plans

Dr. Xiaolin Zhang, PhD, CEO of Dizal, reflected on the global implications of the study: “The global pivotal study demonstrated statistically significant and clinically meaningful benefits of sunvozertinib as a single agent in NSCLC patients with EGFR exon20ins. We are advancing the development of sunvozertinib in the first-line setting through a global phase III study (WU-KONG28).” He emphasized the commitment to accelerating ongoing clinical studies and making the drug available globally as swiftly as possible.

The success of the EZFB regimen in the ARC-9 study marks a significant milestone in the treatment of mCRC, providing a new beacon of hope for patients who have exhausted other options. The combination of etrumadenant and zimberelimab could redefine third-line treatment strategies for mCRC, potentially improving survival outcomes and quality of life for patients facing this challenging diagnosis.

  Arcus Biosciences, ASCO, Cancer treatment, clinical trials, etrumadenant, Gilead Sciences, Metastatic colorectal cancer, zimberelimab