Neoadjuvant nivolumab, ipilimumab, and celecoxib in MMR-proficient and MMR-deficient colon cancers: Final clinical analysis of the NICHE study

3511 Background: The combination of PD-1 and CTLA4 blockade has changed the treatment landscape for several cancer types. Although this treatment is highly effective in metastatic mismatch-repair deficient (dMMR) colorectal cancers, metastatic MMR-proficient (pMMR) tumors do not respond. The NICHE study was the first neoadjuvant immunotherapy study in colon cancer (CC) to show impressive responses in 100% of dMMR ( n= 20) and 27% of pMMR ( n= 15) CC. In contrast, pathologic response to neoadjuvant chemotherapy using standard of care folfox is approximately 5% in dMMR tumors. Here we present the final efficacy data for the original NICHE study cohorts. Methods: Patients with non-metastatic, resectable dMMR or pMMR CC were treated with a single dose of ipilimumab 1mg/kg and two doses of nivolumab 3mg/kg and underwent surgery within 6 weeks. In addition, patients with pMMR tumors were randomized to receive celecoxib. The primary endpoints were safety and feasibility, and secondary endpoints included pathologic response rate and disease-free survival in 30 patients with dMMR and 30 with pMMR tumors. Pathologic response was defined as 50% or less viable tumor rest (VTR), and major pathologic response (MPR) as