Multicenter phase 2 trial of first-line nivolumab plus FOLFOXIRI and bevacizumab for advanced RAS/BRAF-mutated colorectal cancer

The multicenter phase 2 NIVACOR trial in Italy evaluated first-line nivolumab plus FOLFOXIRI and bevacizumab in 73 patients with RAS/BRAF-mutated metastatic colorectal carcinoma (mCRC). The primary endpoint was objective response rate. This endpoint was met was 76.7% (95% CI 65.4-85.8) of patients achieving an objective response, whereas the disease control rate was 97.3% (90.5-99.7). The median progression-free survival was 10.1 months (95% CI 9.0-14.3) and the median overall survival was not reached. Treatment-related adverse events of grade 3 or higher occurred in 48 patients (65.8%). Genomic profiling and RNA sequencing analyses revealed genomic and transcriptomic profiles associated with treatment response in pMMR/MSS patients. Alterations in pathways such as PI3K/AKT, chemokine signaling, and DNA repair showed correlations with treatment activity. The authors conclude that these findings highlight the potential synergy between immune checkpoint inhibitors and cytotoxic chemotherapy in selected patients with pMMR/MSS mCRC.