RecruitingPhase 2NCT05732389

Immunotherapy in Patients With Early dMMR Rectal Cancer

Sponsor

Odense University Hospital

Enrollment

39 participants

Start Date

Feb 1, 2023

Study Type

INTERVENTIONAL

Conditions

Cancer of Rectum

Summary

The purpose of this investigator-initiated, multicenter phase II trial is to evaluate the efficacy and tolerability of nivolumab and ipilimumab in patients with stage 1-3 MSI/dMMR rectal cancer. The primary objective is: Number of patients with complete clinical response after one or two cycles of immunotherapy. Patients will be treated with 1 or 2 cycles of combination immunotherapy: Cycle 1: Nivolumab 3 mg/kg days 1 and 15 \& ipilimumab 1 mg/kg day 1 Cycle 2: Nivolumab 3 mg/kg days 50 and 65 \& ipilimumab 1 mg/kg day 50

Eligibility

Min Age: 18 Years

Plain Language Summary

Simplified for easier understanding

This study tests immunotherapy (using drugs called nivolumab and ipilimumab) as a treatment for people with early-stage rectal cancer that has a specific genetic feature called dMMR (mismatch repair deficient) or MSI (microsatellite instability). These tumours tend to respond very well to immunotherapy. The goal is to see whether immunotherapy alone — without chemotherapy or radiation — can effectively treat or even cure early rectal cancer. **You may be eligible if...** - You are 18 years or older - You have been diagnosed with non-metastatic (not spread) rectal cancer, stage 1 to 3 - Your tumour has been confirmed as dMMR or MSI by testing - You have not had any previous chemotherapy, radiation, or immunotherapy for colorectal cancer - Your blood counts and organ function are in an acceptable range **You may NOT be eligible if...** - You have an active autoimmune disease (conditions where the immune system attacks the body) - You are taking high-dose steroid medication - You have a known allergy to nivolumab or ipilimumab - You are pregnant or planning to become pregnant without using contraception Talk to your doctor to see if this trial is right for you.

This summary was AI-generated to explain the trial in plain language. It is not medical advice. Always discuss eligibility with your doctor before enrolling in a clinical trial.

Interested in this trial?

Get notified about updates and connect with the research team.

Interventions

DRUGNivolumab

Nivolumab is a highly selective fully humanized, IgG4 monoclonal antibody inhibitor of programmed death-1 (PD-1) (17). PD-1 is an inhibitory receptor expressed on the surface of T-cells, B cells, macrophages, and NK cells. Endogenous binding of PD-1 with one of its two ligands PD-L1 and PD-L2 results in production of an inhibitory signal which results in reduction of T-cell proliferation, cytokine production, and cytotoxic activity. This results in significant dampening of the immune response. Nivolumab acts to selectively block the receptor activation of PD-L1 and PD-L2, resulting in a release of PD-1 mediated inhibition of the immune response.

DRUGIpilimumab

Ipilimumab is a fully humanized monoclonal anti-CTLA-4 antibody that acts as an antineoplastic ICI by selectively binding to cytotoxic T-lymphocyte-associated antigen 4, a molecule located on the surface of cytotoxic T-cells, suppressing the immune response (17). Ipilimumab blocks CTLA-4, leading to a continuously active immune response in malignant cells.