The Phoenix Trial: Phase II Trial of Cemiplimab for the Non-operative Management of Localized dMMR Colon Cancer

Primary Objective: •To assess feasibility and success of an organ-sparing strategy in patients with localized dMMR colorectal cancer receiving neoadjuvant cemiplimab. The primary endpoint is rate of endoCR by 6 months. Exploratory Objectives: * To quantify organ-sparing rate at 1 year for all patients treated with one dose of cemiplimab (intent to treat) * To quantify the composite rate of either non-operative management at 1 year or pathological complete response for all patients treated with one dose of cemiplimab (intent to treat) * To quantify the composite rate of either endoCR by 6 months or pathologic complete response for all patients treated with one dose of cemiplimab (intent to treat) * To assess and describe features observed on endoscopy after neoadjuvant cemiplimab * To assess radiographic response to neoadjuvant cemiplimab * To estimate the relapse-free survival, progression-free survival and overall survival in all enrolled participants * To determine the overall rates of pathological response to neoadjuvant cemiplimab in patients who undergo resection after receiving at least one dose of cemiplimab * To determine overall safety of cemiplimab for patients with localized colon cancer * To determine the change in patient-reported symptoms with cemiplimab * To explore the predictive ability of changes in ctDNA for efficacy endpoints * To determine if total mutational burden and genomic alterations correlate with response and extent of benefit from cemiplimab * To correlate tumor-immune microenvironment (for example T-effector cell populations; CD4 subsets; T-regulatory populations; B cell populations; dendritic and macrophage populations) in pre-treatment tumor samples with efficacy endpoints * To compare targeted gene expression profiles of immune-related genes and genes pertaining to common cancer signaling pathways in pre-treatment samples as well as the change in these factors (for cases with both pre-treatment and on-treatment tumor samples) between responders and non-responders