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PD-1 plus CTLA-4 blockade is highly effective in advanced-stage, mismatch repair (MMR)-deficient (dMMR) colorectal cancers, yet not in MMR-proficient (pMMR) tumors. We postulated a higher efficacy of neoadjuvant immunotherapy in early-stage colon cancers. In the exploratory NICHE study (ClinicalTrials.gov: (https://clinicaltrials.gov/ct2/show/NCT03026140)), patients with dMMR or pMMR tumors received a single dose of ipilimumab and two doses of nivolumab before surgery, the pMMR group with or without celecoxib. The primary objective was safety and feasibility; 40 patients with 21 dMMR and 20 pMMR tumors were treated, and 3 patients received nivolumab monotherapy in the safety run-in. Treatment was well tolerated and all patients underwent radical resections without delays, meeting the primary endpoint. Of the patients who received ipilimumab + nivolumab (20 dMMR and 15 pMMR tumors), 35 were evaluable for efficacy and translational endpoints. Pathological response was observed in 20/20 (100%; 95% exact confidence interval (CI): 86-100%) dMMR tumors, with 19 major pathological responses (MPRs, [less than or equal to]10% residual viable tumor) and 12 pathological complete responses. In pMMR tumors, 4/15 (27%; 95% exact CI: 8-55%) showed pathological responses, with 3 MPRs and 1 partial response. CD8.sup.+PD-1.sup.+ T cell infiltration was predictive of response in pMMR tumors. These data indicate that neoadjuvant immunotherapy may have the potential to become the standard of care for a defined group of colon cancer patients when validated in larger studies with at least 3 years of disease-free survival data. Results from the NICHE study show remarkable pathological responses to neoadjuvant combination immunotherapy in patients with early-stage colon cancer and uncover potential biomarkers of response., Author(s): Myriam Chalabi [sup.1] [sup.2] [sup.3] , Lorenzo F. Fanchi [sup.2] [sup.4] , Krijn K. Dijkstra [sup.2] [sup.4] , José G. Van den Berg [sup.5] , Arend G. Aalbers [sup.6] [...]

Harnessing immune cells to target tumours is a growing trend. The results of a clinical trial combining such treatment with other standard therapies for gastric cancer have altered medical practice -- and more changes are to come. Clinical trial results point to a new way to treat gastric cancer., Author(s): Myriam Chalabi Author Affiliations: Stomach cancer gets a triple punch of therapy Gastric cancer is a highly aggressive disease. Writing in Nature, Janjigian et al. [sup.1] present clinical data [...]