LBA7 Neoadjuvant immune checkpoint inhibition in locally advanced MMR-deficient colon cancer: The NICHE-2 study

Abstract

Neoadjuvant immunotherapy has shown promising responses in several cancer types. For colon cancer (CC), NICHE was the first neoadjuvant immunotherapy study to show pathologic responses in 100% of dMMR tumors. Importantly, disease-free survival (DFS) in patients (pts) with stage III dMMR CC is similar to that of pMMR pts, with 3-year recurrence risks of over 40% in high-risk (T4 and/or N2) stage III tumors despite adjuvant chemotherapy. Improving outcome for this patient population is urgently needed. In the NICHE-2 study, pts with non-metastatic dMMR CC were treated with one dose of ipilimumab (1mg/kg) and two doses of nivolumab (3mg/kg) and underwent surgery ≤6 weeks of registration. The co-primary endpoints were safety (ITT) and 3-year DFS (PP). Secondary endpoints included major pathologic response (MPR) and complete response (pCR) rates. Pathologic response was defined as ≤50% residual viable tumor (RVT), and MPR as ≤10% RVT. Here we present safety and pathologic response data. A total of 112 pts were treated. Grade 3-4 immune-related adverse events were observed in 3 (3%) patients and only 3 pts experienced delay in surgery, meeting the safety primary endpoint. In the PP population (n=107), baseline radiologic assessment revealed 89% stage III, 77% high-risk stage III (Table), and 64% T4 tumors. With a median time from first dose to surgery of 5 weeks, pathologic response was observed in 106/107 (99%) pts, consisting of 102/107 (95%) MPR and 4 (4%) PR. PCR was observed in 72/107 (67%) pts. At a median follow-up of 13 months (range 1-57), none of the pts had disease recurrence.Table: LBA7Pathologic responseMPRpCRClinical stageI/II (n = 12)11 (92%)9 (75%)Low risk IIIa/b (n = 13)13 (100%)10 (77%)High risk IIIa/b (n = 17)16 (94%)10 (59%)High risk IIIc (n = 65)62 (95%)43 (66%)Total (n = 107)102 (95%)72 (67%) Open table in a new tab In NICHE-2 we confirm the previously reported pathologic responses to short-term neoadjuvant nivolumab plus ipilimumab in a large cohort of dMMR CC pts, with an MPR rate of 95%, including 67% pCR. The first survival data suggest a strong potential for neoadjuvant immunotherapy to become standard of care and allow further exploration of organ-sparing approaches.