611TiP - Nivolumab, ipilimumab and COX2-inhibition in early stage colon cancer

Abstract

Background: For the 4% of patients with metastatic mismatch repair deficient (dMMR) colorectal cancers, impressive responses are seen with anti-PD1 monotherapy, with response rates up to 40%. Data in patients with non-metastatic colon cancers (CCs) are lacking. Both MSS and MSI early stage CCs show a higher proportion of T-cell infiltration, when compared to metastatic disease. Also, preclinical work has shown improved responses to anti-PD1 therapy by addition of COX (2)-inhibition, suggesting this could be a useful adjuvant that might help induce responses in MSS CRCs. Trial design: The NICHE trial is a single center, investigator-initiated study, in which patients with newly diagnosed colon cancer who have no signs of distant metastases will be treated with short-term immunotherapy ± COX2-inhibition. Treatment will be given in the window period until surgical resection of the tumor. In this exploratory study, the primary objective will be to determine the safety and feasibility of pre-operative immunotherapy in CC. Secondary objectives include exploring the immune activating capacity of immunotherapy in early stage CCs and the added effects of COX2 inhibition, changes in immune suppressive pathways and the correlation of mutational load to putative markers of response. After additional tumor biopsies are taken via endoscopy, patients with dMMR tumors will all be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15. Patients with MSS tumors will be randomized to receive celecoxib 200mg once daily in combination with abovementioned treatment. After 5-6 weeks, patients will undergo surgery, where tumor and normal tissue will again be harvested. When deemed advisable by the pathology report, standard adjuvant treatment with chemotherapy will be offered. A total of 30 patients with MSS tumors and 30 patients with MSI tumors will be enrolled. Recruitment for this study is ongoing and currently two patients have been enrolled. Conclusion: This is, to our knowledge, the first study exploring pre-operative immunotherapy in patients with non-metastatic CC and will hopefully help identify mechanisms that interfere with clinical activity of immunotherapy, and to develop future strategies and combinations for CRC. Clinical trial identification: 2016-002940-17. Release date: January 2017 Legal entity responsible for the study: Netherlands Cancer Institute Funding: Bristol-Myers-Squibb Disclosure: D. Cullen: Employment with BMS. J.B. Haanen: Ad board BMS. All other authors have declared no conflicts of interest.