Data from The Randomized Phase II ARC-9 Study of Etrumadenant-Based Therapy versus Regorafenib in Patients with Previously Treated Metastatic Colorectal Cancer

作者：Michael Cecchini, Sae‐Won Han, Soo Hyun Lee, Keun‐Wook Lee, Scott Kopetz, Jonathan D. Mizrahi, Yong Sang Hong, François Ghiringhelli, Antoîne Italiano, David Tougeron, Brandon Beagle, Mathew Boakye, Tingting Zhao, Vivek Khemka, Zev A. Wainberg · 年份：2026 · DOI：10.1158/1078-0432.c.8568730 · 研究领域：Colorectal Cancer Treatments and Studies、Cancer Immunotherapy and Biomarkers、Adenosine and Purinergic Signaling

<div>AbstractPurpose:Targeting the adenosine pathway may enhance the efficacy of chemo/immunotherapy regimens in patients with heavily pretreated advanced metastatic colorectal cancer (mCRC), for whom treatment options are limited.Patients and Methods:The phase II ARC-9 study, Cohort B (NCT04660812), evaluated the efficacy and safety of etrumadenant (A2a and A2b receptor antagonist), zimberelimab (anti–PD-1 mAb), FOLFOX, and bevacizumab (EZFB) versus regorafenib in patients with third-line mCRC who previously progressed on oxaliplatin- and irinotecan-containing regimens.Results:From September 21, 2021, to September 12, 2022, 112 patients were randomized 2:1 to EZFB (n = 75) or regorafenib (n = 37). As of November 13, 2023, the median survival follow-up was 20.4 months. The primary endpoint of progression-free survival (PFS) was improved with EZFB (6.2 months) versus regorafenib [2.1 months; hazard ratio (HR), 0.27; 95% confidence interval (CI), 0.17–0.43; nominal P < 0.0001], as was the secondary endpoint of overall survival (OS; EZFB, 19.7 months; regorafenib, 9.5 months; HR, 0.37; 95% CI, 0.22–0.63; nominal P = 0.0003). The confirmed overall response rate was 17% (90% CI, 10.6%–26.1%) with EZFB and 3% (90% CI, 0.1%–12.2%) with regorafenib. Treatment-emergent adverse events (TEAE), grade ≥3 TEAEs, an...