Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair–Deficient Colon Cancer

June 2024 Cancer trials Vanessa Vernimmen

Mismatch repair–deficient (dMMR) tumours can be found in 10-15% of patients with non-metastatic colon cancer. In these patients, the efficacy of chemotherapy is limited. The use of neoadjuvant immunotherapy has shown promising results, but data from studies of this approach are limited.1

In the NICHE study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy plus novel IO combinations. This treatment will be given until surgical resection of the tumour and the duration of treatment will be approximately six weeks.2


A phase II study in which patients with non-metastatic, locally advanced, previously untreated dMMR colon cancer were treated with neoadjuvant nivolumab plus ipilimumab was conducted. The two primary end-points were safety, defined by timely surgery, and 3-year disease-free survival. Secondary end-points included pathological response and results of genomic analyses.


Of the 115 enrolled patients, 113 (98%; 97.5% confidence interval [CI], 93-100) underwent timely surgery; two patients had surgery delayed by more than two weeks. Grade 3/4 immune-related adverse events occurred in five patients (4%), and none of the patients discontinued treatment due to adverse events. Among the 111 patients included in the efficacy analysis, a pathological response was observed in 109 (98%; 95% CI, 94-100), including 105 (95%) with a major pathological response (defined as ≤10% residual viable tumour) and 75 (68%) with a pathological complete response (0% residual viable tumour). With a median follow-up of 26 months (range, 9-65), no patients have had recurrence of disease.


In 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.1


1. Chalabi M, Verschoor YL, Batista Tan P, et al. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair–Deficient Colon Cancer. N Engl J Med. 2024;390(21):1949-58.

2. ID NCT03026140. Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL). Accessed on 24 June 2024.