Single-center phase 2 trial of neoadjuvant nivolumab plus relatlimab for locally advanced MMR-deficient colon cancer

Mismatch repair deficiency (dMMR) is found in approximately 15% of non-metastatic colon cancers (CCs) and is characterized by hypermutated and highy immunogenic tumors. The phase 2 NICHE-3 study, at the Netherlands Cancer Institute (Amsterdam), evaluated the neoadjuvant combination of nivolumab (anti-PD-1) and relatlimab (anti-LAG-3) in patients with locally advanced dMMR CC. All patients underwent R0 surgery. Pathologic responses were observed in 57 of 59 patients (97%; 95% CI 88-100), meeting the primary endpoint; major pathologic responses (≤10% viable tumor) were seen in 54 patients (92%; 81-97); and pathologic complete response were observed in 40 patients (68%; 54-79). With a median follow-up of 8 months (range 2-19), one patient had recurrence of disease. The safety profile was acceptabe with immune-related adverse events in 80% of patients (grade 3 or 4 in 10%). The authors conclude that the neoadjuvant combination of nivolumab and relatlimab had promising activity in patients with locally advanced dMMR CC.