Neoadjuvant nivolumab/relatlimab demonstrates 100% pathological response in MMRd colon cancer

Recently, NICHE-2 showed impressive pathological response rates of neoadjuvant nivolumab/ipilimumab in patients with mismatch repair deficient (MMRd) colon cancer. Now, NICHE-3 shows equally impressive pathological complete response (pCR) rates after nivolumab/relatlimab neoadjuvant treatment of MMRd colon cancer.

MMRd is amongst the best predictive biomarkers of immunotherapy response. Approximately 10–15% of all non-metastatic colon cancers are MMRd. In the NICHE-2 study, neoadjuvant nivolumab/ipilimumab in MMRd colon cancers resulted in 95% major pathologic responses (MPR), including 67% pCR within 6 weeks of treatment [1].

In melanoma patients, the combination of nivolumab and LAG-3 inhibitor relatlimab showed a favourable toxicity profile and promising efficacy in the neoadjuvant setting [2]. Therefore, the NICHE-3 study (NCT03026140) explores the efficacy and safety of this regimen in participants with non-metastatic MMRd colon cancer. The primary endpoint of NICHE-3 is the pCR. Dr Yara Verschoor (Netherlands Cancer Institute, the Netherlands) presented the results from the stage 1 cohort of NICHE-3 [3].

Stage 1 enrolled 19 participants with resectable, locally advanced (at least cT3 and/or N+), MMRd colon cancer. Participants were treated with 2 doses of nivolumab plus relatlimab at a 4-week interval, followed by surgery within 8 weeks of registration.

With only 5% grade 3 adverse events, neoadjuvant therapy with nivolumab/relatlimab was generally well tolerated. “All participants were fully treated and all participants underwent surgery without delay,” said Dr Verschoor. A 100% R0 rate was observed at surgical resection. All participants showed a pathological response (89% MPR, 79% pCR). None of the participants presented lymph node metastases in the surgical resection specimen, therefore none of the participants received adjuvant chemotherapy.

“With 100% of participants revealing a pathological response, stage 1 of NICHE-3 met its endpoint,” concluded Dr Verschoor. “As a result, accrual of stage 2 of an extension cohort with 40 participants has started.”

1. 
   
   1. Chalabi M, et al. Ann Oncol. 2022;33(suppl_7):S808–S869.
   2. Amaria RN, et al. Nature 2022;611:155–160.
   3. Verschoor YL, et al. Neoadjuvant nivolumab plus relatlimab (anti-LAG3) in locally advanced MMR-deficient colon cancers: The NICHE-3 study. Abstract LBA31, ESMO 2023, 20–24 October, Madrid, Spain.

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Posted on 18 December, 202328 March, 2024