Multicenter phase 2 trial of neoadjuvant immunotherapy for mismatch repair-deficient colon cancer in the Netherlands

Neoadjuvant immune checkpoint blockade induces high pathological response rates in patients with locally advanced mismatch repair-deficient (dMMR) colon cancer. The phase 2 NICHE-2 trial , at six centers in the Netherlands evaluated long-term survival outcomes among these patients. The trial enrolled patients with previously untreated, clinical stage 2 or 3, resectable dMMR colon cancer. Patients received a single dose of ipilimumab on day 1 and two doses of nivolumab on days 1 and 15, followed by surgery. Primary endpoint was 3-year disease-free survival (DFS) rate; exploratory endpoint was 5-year overall survival (OS) rate. A total of 115 patients were treated and 111 were included in the per-protocol population. At data cutoff, the postoperative median follow-up was 58.7 months (IQR 49.0-72.9). The 3-year DFS rate was 100% (97.5% CI 100-100). After a median follow-up of 60.4 months (IQR 50.6-74.1) from study enrollment, the 5-year OS rate was 100% (95% CI 100-100). Among patients with available plasma samples, circulating tumor (ct)DNA was detected in 92% at baseline, and ctDNA clearance was observed in 45% of patients after the first cycle in week 2 and in 82% after the second cycle before surgery. Assessment for minimal residual disease after surgery revealed that all patients were ctDNA negative. The authors conclude that in patients with locally advanced dMMR colon cancer, treatment with ipilimumab and nivolumab before surgery resulted in 3-year DFS rate and 5-year OS rate of 100%.