Immunotherapy in Patients With Early dMMR Rectal Cancer

NCT05732389 | Recruiting Phase 2 DMC

• 1 other identifier: KFE nr. 22.20
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 5

Brief 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

Outcome Measures

Primary Outcomes (1)

• Complete clinical response

  Proportion of patients with complete clinical response Complete clinical response will be defined as no visible or palpable tumor examined by rectal exploration (if low tumors), endoscopy and MR-scan. Patients with definite but less than complete regression BUT with a representative biopsy without viable tumor cells will also be classified as cCR in this trial.

  Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)

Secondary Outcomes (7)

• Complete biological response

  Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)

• 12 months recurrence

  after 12 months

• Respons rate

  after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)

• Adverse events

  after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)

• Bio-marker predictive models for treatment response and survival.

  after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)

Study Arms (1)

nivolumab + ipilimumab

EXPERIMENTAL

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

Drug: Nivolumab; Drug: Ipilimumab

Interventions

Nivolumab DRUG

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.

Also known as: Opdivo

nivolumab + ipilimumab

Ipilimumab DRUG

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.

Also known as: Yervoy

nivolumab + ipilimumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years.
• Histologically verified non-metastatic rectal cancer stage 1-3.
• No indication for local therapy like TEM.
• Histologically verified dMMR or MSI.
• Performance status (WHO) of 0-1.
• No previous chemotherapy, radiotherapy or immunotherapy for colorectal cancer
• Adequate haematological function defined as neutrophils ≥ 1.5 x 109/l and platelets ≥ 100 x 109/l.
• Adequate organ function (bilirubin ≤ 1.5 x UNL (upper normal limit), GFR (may be calculated) \> 30 ml/min.
• Women of childbearing potential must have been tested negative in a serum pregnancy test within five days prior to registration. Fertile patients must agree to use a highly effective method of birth control. (i.e., pregnancy rate of less than 1 % per year) (Appendix 1) during the study and for six months after the discontinuation of study medication.
• Has provided written informed consent prior to performance of any study procedure.
• Written informed consent must be obtained according to the local Ethics Committee requirements.

You may not qualify if:

• Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
• Subjects with active, known, or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enrol.
• Known allergy or intolerance to any of the drugs used (nivolumab and ipilimumab).

Sponsors & Collaborators

• Odense University Hospital: lead
• Rigshospitalet, Denmark: collaborator
• Zealand University Hospital: collaborator
• Aalborg University Hospital: collaborator
• Aarhus University Hospital: collaborator
• Bispebjerg Hospital: collaborator
• Herlev and Gentofte Hospital: collaborator
• Vejle Hospital: collaborator

Study Sites (5)

Aalborg University Hospital

Aalborg, 9000, Denmark

RECRUITING

Aarhus University Hospital

Aarhus, 8200, Denmark

RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Department of Oncology, Odense University Hospital

Odense, 5000, Denmark

RECRUITING

Zealand University Hospital

Roskilde, 4000, Denmark

RECRUITING

MeSH Terms

Conditions

Rectal Neoplasms

Interventions

Nivolumab; Ipilimumab

Condition Hierarchy (Ancestors)

Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Line S Tarpgaard, MD, Phd

  Department of Oncology, Odense University Hospital, Denmark

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie Bach

CONTACT

30714320; Julie.Kristina.Bach@rsyd.dk

Christian P Olsen, Phd

CONTACT

24342488; Christian.pilely.olsen@rsyd.dk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: February 17, 2023
• Study Start: February 1, 2023
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): February 1, 2052
• Last Updated: August 7, 2025

Record last verified: 2025-07

Locations

DK (5)