Multicenter phase 2 trial of neoadjuvant immunotherapy in locally advanced mismatch repair-deficient colon cancer

Mismatch repair-deficient (dMMR) tumors are found in 10% to 15% of patients with nonmetastatic colon cancer. In these patients, efficacy of chemotherapy is limited. The multicenter phase 2 NICHE-2 trial in The Netherlands evaluated neoadjuvant chemotherapy for locally advanced dMMR colon cancer. Patients received neoadjuvant nivolumab plus ipilimumab. Co-primary endpoints were timely surgery (≤ 2 week delay of planned surgery) and 3-year disease-free survival. Of 115 patients, 113 (98%; 97.5% CI 93-100) underwent timely surgery. Among 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%), including 105 (95%) with a major pathological response and 75 (68%) with a pathological complete response. With a median follow-up of 26 months (range 9-65) none of the patients had recurrence of disease. The authors conclude that among patients with locally advanced dMMR colon cancer, neoadjuvant nivolumab plus ipilimumab had an acceptable safety profile and led to a pathological response in a high proportion of patients.