AZUR-4, a Phase 2, Open Label, Randomized Study of Neoadjuvant Dostarlimab Plus CAPEOX Versus CAPEOX in Previously Untreated T4N0 or Stage III Mismatch Repair Proficient/Microsatellite Stable Resectable Colon Cancer

Background Recent evidence has suggested that neoadjuvant chemotherapy may provide clinical benefit for patients with locally advanced colon cancer. Immunotherapy may provide additive or synergistic effects when combined with chemotherapy. This study's objective is to assess the efficacy, safety, and tolerability of neoadjuvant dostarlimab in combination with capecitabine-oxaliplatin (CAPEOX) versus CAPEOX in patients with T4N0 or stage III mismatch repair proficient/microsatellite stable (pMMR/MSS) resectable colon cancer. Methods AZUR-4 (NCT06567782) is a multicenter, phase 2, open-label, randomized (3:1 ratio) study of 120 patients across multiple countries. Eligible patients are aged ≥18 years with resectable pMMR/MSS colon adenocarcinoma with no prior treatment. Four cycles (21 days) of CAPEOX ± dostarlimab will be administered as neoadjuvant treatment. After completing neoadjuvant treatment, patients will undergo surgery 3–6 weeks later, with additional adjuvant chemotherapy administered after surgery at the investigator's discretion; no additional dostarlimab will be administered. Primary endpoints are major pathological response, determined by local assessment, and safety. Secondary endpoints will assess the feasibility and pathological response to the regimen. Exploratory endpoints include biomarker readouts and pathological response rate in biomarker subsets. Conclusions AZUR-4 will evaluate the effect of neoadjuvant dostarlimab + CAPEOX in patients with previously untreated T4N0 or stage III pMMR/MSS resectable colon cancer, a population for whom improved treatments are urgently needed. The robust sampling and advanced analysis of pretreatment and posttreatment blood, tissue, and tumor samples planned for this trial should assist in elucidating immune profile analyses to support the discovery of novel predictive biomarkers in this population. Trial registration This trial is registered at clinicaltrials.gov (NCT06567782)