KEY TAKEAWAYS
- The NICHE-3 phase 2 trial aimed to assess Nivolumab/Relatlimab’s neoadjuvant efficacy and toxicity in non-metastatic dMMR colon cancer.
- The result demonstrated the efficacy of neoadjuvant nivolumab/relatlimab in dMMR colon cancer patients.
Neoadjuvant immunotherapy has provided effective results in fighting diverse tumors. In the NICHE-2 study, major pathologic responses (MPR) were achieved with 95% efficacy, along with 67% pathologic complete responses (pCR), in neoadjuvant nivolumab/ipilimumab in MMR deficient (dMMR) colon cancer patients.
In the NICHE-3 phase 3 study, researchers aimed to explore nivolumab/relatlimab in non-metastatic dMMR colon cancer. Patients with locally advanced dMMR colon cancer received two doses of nivolumab (480 mg) and relatlimab (480 mg) with a 4-week gap, followed by surgery within 8 weeks. Pathologic response was defined as 50% or less residual viable tumor (RVT), and major pathologic response (MPR) as ≤10% RVT.
The primary endpoint was the pathologic response rate. Following a Simon-2-stage design, at least 15 out of 19 responders were required in stage 1 to proceed to stage 2. This presentation focuses on the prespecified analysis of pathologic response outcomes from stage 1.
As a result, out of 19 treated patients who underwent surgery without delays, 14 (74%) experienced Grade 1-2 immune-related adverse events (irAEs), with infusion-related reactions being the most common (43%). Only one patient (5%) had a grade 3 irAE (hyperthyroidism). Endocrinopathy requiring supplementation occurred in 4 (21%) patients, including 1 with hypothyroidism and 3 with hypophysitis leading to secondary adrenal and/or thyroid insufficiency.
Among the patients, no grade 4-5 irAEs were reported. With a median of 7.4 weeks between the first dose and surgical resection, the treatment resulted in a 79% pathological complete response (pCR) rate, 89% major pathological response (MPR) rate, and a 100% overall pathologic response rate among the 19 patients.
The interventional NICHE-3 study demonstrated highly promising early results for neoadjuvant nivolumab/relatlimab in dMMR colon cancer, with 100% pathologic response and 79% complete pathologic response.
Clinical Trial: https://clinicaltrials.gov/study/NCT03026140
Verschoor YL, van den Berg J, Balduzzi S, van Blijderveen JC, Oosterling S, Burger P, Aukema T, Vogten T, Dokter S, Beets-Tan R, Lent AV, Beets G, van Leerdam M, Haanen JBAG, Chalabi M. Neoadjuvant Nivolumab Plus Relatlimab (Anti-LAG3) in Locally Advanced MMR-Deficient Colon Cancers: The NICHE-3 Study. ESMO 2023 Abstract LBA31.
