Both NICHE-2 & NICHE-3 Trials Show High Efficiency of Short Neoadjuvant Immunotherapy in dMMR Colon Cancer

Nov 11, 2024

Photo Credit: Mohammed Haneefa Nizamudeen

Two neoadjuvant cycles of nivolumab/ipilimumab or nivolumab/relatlimab induced high rates of pathological responses in patients with dMMR colon cancer, results from the NICHE-2 and NICHE-3 studies showed. Neoadjuvant nivolumab/ipilimumab comes with an unprecedented 3-year disease-free survival rate of 100%.

Previously, the phase 2 NICHE trial (NCT03026140) demonstrated the safety and efficacy of two cycles of neoadjuvant nivolumab (plus ipilimumab in the first cycle), with a high pathological response rate (98%, 95% major pathological response) in patients with locally advanced mismatch-repair deficient (dMMR) colon cancer¹. Myriam Chalabi, MD, from the Netherlands Cancer Institute, now presented 3-year disease-free survival (DFS) data of NICHE-2². With a median follow-up from surgery of 36.6 months, the 3-year DFS was 100%. Of note, 105 out of 111 participants had at least 2 years of follow-up.

In addition, the dynamics of ctDNA were studied in NICHE-2. At baseline, 92% of the participants had detectable ctDNA, decreasing to 55% after only one cycle of neoadjuvant immunotherapy and 17% pre-surgery. ctDNA clearance was higher in participants with complete pathological response versus those with major pathological response (92% vs 70% pre-surgery). Three weeks after surgery (MRD timepoint), all participants were ctDNA negative. “So, ctDNA may aid in organ preservation,” Dr. Chalabi said.

Another part of the NICHE trial, termed NICHE-3, aimed to evaluate the safety and efficacy of two cycles of neoadjuvant nivolumab plus relatlimab in patients with locally advanced dMMR colon cancer. Peter de Gooyer, MD, from the Netherlands Cancer Institute, presented the results³. NICHE-3 enrolled 59 participants (68% T4, 63% cN+) of whom 56 received both treatment cycles.

Pathological responses were observed in 97% of the participants, with 92% major pathological responses and 68% complete responses. At a median follow-up of 8 months, all patients were alive and DFS was 98%. A low rate of grade 3–4 immune-related AEs was observed: 10% (n=6). The median time from immunotherapy to surgery was 7.6 weeks and 100% R0 was achieved.

Based on these results, Dr. De Gooyer concluded that “nivolumab/relatlimab is highly effective in inducing pathological responses, comparable to nivolumab/ipilimumab.”

Medical writing support was provided by Marten Dooper.