Immunotherapy in Patients With Early dMMR Rectal Cancer

Phase 2

Recruiting

• Conditions: Cancer of Rectum
• Interventions: Drug: Nivolumab; Drug: Ipilimumab

• Registration Number: NCT05732389
• Lead Sponsor: Odense University Hospital

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-01-17
• Study Start: 2023-02-01
• Study First Submitted QC: 2023-02-07
• Study First Posted: 2023-02-17
• Status Verified: 2025-07
• Last Update Submitted: 2025-08-01
• Last Update Posted: 2025-08-07
• Primary Completion: 2027-07
• Study Completion: 2052-02-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• 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.

Exclusion Criteria

• Any other condition or therapy, which in the investigator's opinion may pose a risk to the patient or interfere with the study objectives.
• Concomitant use of systemic glucocorticoids more than the equivalent dose to tablet prednisolone 10 mg/day. Treatment with systemic glucocorticoids must end no later than two weeks before inclusion.
• 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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
nivolumab + ipilimumab	Nivolumab	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
nivolumab + ipilimumab	Ipilimumab	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

Primary Outcome Measures

Name	Time	Method
Complete clinical response	Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)	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.

Secondary Outcome Measures

Name	Time	Method
Complete biological response	Evaluated at day 93 (+/- 7 days) after one or two cycles of immunotherapy. (Each cycle is 7 weeks)	Proportion of patients with complete biological response
12 months recurrence	after 12 months	Proportion of patients without any sign of recurrence after 12 months.
Respons rate	after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)	Response rate according to mrTRG.
Adverse events	after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)	Adverse events assessed by the investigator according to the definitions in NCI-CTC, version 5.0
Bio-marker predictive models for treatment response and survival.	after 1 or 2 cycles of immunotherapy. (Each cycle is 7 weeks)	Correlation between bio-markers (ctDNA and CEA) and outcome.
Quality of life (EORCT QLQ-C30)	after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)	Change in Quality of life (EORCT QLQ-C30)
Quality of life (EORCT QLQ-CR29)	after 1 or 2 cycles of immunotherapy and months 4, 10, 16, and 24. (Each cycle is 7 weeks)	Change in Quality of life (EORCT QLQ-CR29)

Trial Locations

Locations (5)

Aalborg University Hospital; 🇩🇰 Aalborg, Denmark

Aarhus University Hospital; 🇩🇰 Aarhus, Denmark

Rigshospitalet; 🇩🇰 Copenhagen, Denmark

Department of Oncology, Odense University Hospital; 🇩🇰 Odense, Denmark

Zealand University Hospital; 🇩🇰 Roskilde, Denmark