There is increasing evidence that the anti-tumour immune response plays a central role in the clinical outcome in colorectal cancer (CRC). The programmed death 1 (PD-1) pathway is a negative feedback system that is up-regulated in many tumours and the surrounding microenvironment. Blockade of this pathway with PD-1 monoclonal antibodies leads to an increase in the cancer-directed immune response and has led to remarkable responses in many cancer types.
PD-1 antibody studies have had mixed results in CRC patients overall. However, up to 15 percent of patients with operable CRC have deficient deoxyribonucleic acid (DNA) mismatch repair (MMR) machinery (dMMR). Metastatic CRC patients with dMMR tumours have a significantly improved response to PD-1 inhibitors and improved survival compared to chemotherapy, as shown in the Keynote-177 trial.
The purpose of the Neo-POLEM study is to determine if MSI high, early CRCs respond to or benefit from PD-1 vaccine IMU-201 (PD1-Vaxx). The primary objective is to determine the rate of Major Pathological Response (MPR), determined by ≤10% viable tumour cells after administering neoadjuvant PD-1 vaccine IMU-201 (PD1-Vaxx). If this study shows a significant response in this group of patients, neo-adjuvantPD-1 vaccine may become an option for dMMR early colorectal cancers.
Prof Tim Price
Thursday, 16 November
Session 2: Colon Cancer (Early)