Nivolumab/relatlimab neoadjuvant treatment of deficient mismatch repair colon cancer shows impressive pathological response rates.

Deficient mismatch repair (dMMR) is among the best predictive biomarkers of immunotherapy response. Approximately 10% to 15% of all nonmetastatic colon cancers are dMMR. In the NICHE-2 study, neoadjuvant nivolumab/ipilimumab in dMMR colon cancers resulted in 95% major pathologic responses, including 67% pathologic complete responses (pCR) within 6 weeks of treatment [1].

In melanoma patients, the combination of nivolumab and LAG-3 inhibitor relatlimab showed a favorable 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 nonmetastatic dMMR colon cancer. The primary endpoint of NICHE-3 is the pathologic response rate. 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+), dMMR 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 Verschoor. A 100% R0 rate was observed at surgical resection. All participants showed a pathological response (89% major pathological response, 79% complete response). 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.”

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