NICHE-2 and NICHE-3 show high efficacy of short neoadjuvant immunotherapy in dMMR colon cancer

Two neoadjuvant cycles of nivolumab/ipilimumab or nivolumab/relatlimab induced high rates of pathological responses in patients with mismatch-repair deficient (dMMR) colon cancer in the phase 2 NICHE-2 and NICHE-3 studies. Neoadjuvant nivolumab/ipilimumab comes with an unprecedented 3-year disease-free survival (DFS) rate of 100%.

Previously, the phase 2 NICHE trial (NCT03026140) demonstrated the safety and efficacy of 2 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 dMMR colon cancer [1]. Dr Myriam Chalabi (Netherlands Cancer Institute, the Netherlands) now presented 3-year DFS data of NICHE-2, while Dr Peter de Gooyer (Netherlands Cancer Institute, the Netherlands) presented the results of the NICHE-3 study [2,3].

In the NICHE-2 study, the 3-year DFS was 100% with a median follow-up from surgery of 36.6 months [2]. 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 1 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.

The NICHE-3 study, another part of the NICHE trial, aimed to evaluate the safety and efficacy of 2 cycles of neoadjuvant nivolumab plus relatlimab in patients with locally advanced dMMR colon cancer [3]. 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 participants were alive and DFS was 98%. A low rate of grade 3–4 immune-related adverse events 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 with nivolumab/ipilimumab.”

1. Chalabi M, et al. N Engl J Med 2024;390:1949-1958.
2. Chalabi M, et al. Neoadjuvant immunotherapy in locally advanced MMR-deficient colon cancer: 3-year disease-free survival from NICHE-2. Abstract LBA24, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
3. De Gooyer P, et al. Neoadjuvant nivolumab (nivo) plus relatlimab (rela) in MMR-deficient colon cancer: Results of the NICHE-3 study. Abstract 503O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024