Immunotherapy in Patients With Early dMMR Rectal Cancer

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

Conditions

• Cancer of Rectum

Interventions

DRUG

Nivolumab

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.

DRUG

Ipilimumab

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.

Sponsors & Collaborators

• Rigshospitalet, Denmark

  collaborator OTHER

• Zealand University Hospital

  collaborator OTHER

• Aalborg University Hospital

  collaborator OTHER

• Aarhus University Hospital

  collaborator OTHER

• Bispebjerg Hospital

  collaborator OTHER

• Herlev and Gentofte Hospital

  collaborator OTHER

• Vejle Hospital

  collaborator OTHER

• Odense University Hospital

  lead OTHER

Principal Investigators

• Line S Tarpgaard, MD, Phd · Department of Oncology, Odense University Hospital, Denmark

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-02-01

Primary Completion

2027-07-31

Completion

2052-02-29

Countries

• Denmark

Study Locations