Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (NICHE)

March 3, 2026 updated by: The Netherlands Cancer Institute

Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer (Amended Protocol of: Nivolumab, Ipilimumab and COX2-inhibition in Early Stage Colon Cancer: an Unbiased Approach for Signals of Sensitivity: The NICHE TRIAL)

In this exploratory study, patients with stage 1-3 adenocarcinoma of the colon with no signs of distant metastases will be treated with short-term immunotherapy + novel IO combinations (i.e. anti-IL 8, COX2-inhibitors, anti-LAG3). This treatment will be given during the window period until surgical resection of the tumor. The duration of treatment will be in between approximately 6 and 12 weeks.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

In this multi-center, open-label, exploratory study, the investigators will enroll 60 patients within two years, including 30 patients with MSS tumors and 30 patients with MSI tumors. Patients with MSS tumors will be randomized to either group 1 or 2. Patients with MSI tumors will all be allocated to group 1.

Patients in group 1 will be treated with a single dose of ipilimumab 1mg/kg on day 1 and two cycles of nivolumab 3mg/kg on day 1 and 15, respectively.

Patients in group 2 will be treated with a single dose of ipilimumab 1mg/kg on day 1, two cycles of nivolumab 3mg/kg one day 1 and 15 and celecoxib daily until the day before surgery.

The study was amended in May 2020 to enroll an additional 70 patients in the MSI cohort after the first 30 patients, making a total of 100 patients with MSI tumors. A formal sample size calculation and primary endpoint of 3-year disease-free-survival (DFS) for this group was added.

The study was amended in July 2021 to add a new cohort, cohort 4, for patients with pMMR/MSS tumors. Once accrual of 30 evaluable patients in group 2 was completed, a new cohort opened in which patients will receive nivolumab plus anti-IL8 (BMS-986253).

The study was amended in November 2022 to add cohort 5 and 6, both in which patients will receive nivolumab plus relatlimab (anti-LAG3). Patients with pMMR/MSS tumors will be randomized 1:1 between cohort 4 and cohort 5, patients with dMMR/MSI tumors will be enrolled in cohort 6.

Accrual for cohort 4 was reached in July 2023. In April 2024, accrual for cohort 6 was reached. Per April 2024 only cohort 5 is open for recruitment.

The study was amended in April 2025 to add cohort 7 and 8. Patients with dMMR/MSI tumors will be randomized 1:1 between cohort 7 and 8, in which they will receive 3 cycles of nivolumab + relatlimab or 3 cycles of nivolumab monotherapy respectively. Per June 2025, cohort 5, 7 and 8 are open for recruitment.

Accrual was reached for cohort 8 in February 2026. As February 2026 only cohorts 5 and 7 are open for recruitment. This also means that patients with dMMR/MSI tumors will no longer be randomized but automatically be registered in cohort 7 (and receive 3 cycles of nivolumab + relatlimab).

Study Type

Interventional

Enrollment (Estimated)

353

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Netherlands
      • Amsterdam, Netherlands
        • Recruiting
        • OLVG
        • Contact:
          • A van Lent
      • Amsterdam, Netherlands, 1066CX
        • Recruiting
        • Marieke van de Belt
        • Contact:
      • Eindhoven, Netherlands
        • Recruiting
        • Catharina Ziekenhuis
        • Contact:
          • P Burger
      • Haarlem, Netherlands
        • Recruiting
        • Spaarne Ziekenhuis
        • Contact:
          • S Oosterling
      • Hilversum, Netherlands
        • Not yet recruiting
        • Tergooi
        • Contact:
          • E. Hendriks
      • The Hague, Netherlands
        • Not yet recruiting
        • Haga ziekenhuis
        • Contact:
          • T Aukema

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion criteria:

  • Signed written informed consent
  • Patients at least 18 years of age

  • Non-metastatic adenocarcinoma of the colon (and rectosigmoid considered as nonrectal and not undergoing neoadjuvant treatment)

    • No signs of distant metastases on CT-scan and physical examination;
    • dMMR cohorts 3+6: >cT3 and/or N+

Exclusion criteria:

  • No signs of distant metastases
  • No signs of obstruction or macroscopic bleeding or suspicion of perforation
  • Colonoscopy must be performed after registration to obtain study-specific biopsies. If biopsies are not possible, patients cannot be included in the study
  • WHO performance status of 0 or 1
  • No previous treatment with immune checkpoint inhibitors targeting CTLA-4, PD-1 or PD-L1
  • For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors at registration and no active peptic ulcer, gastrointestinal bleeding, unstable ischemic heart disease of thrombus etiology or significant established ischemic heart disease, peripheral arterial disease and/or cerebrovascular disease
  • No radiotherapy prior to or planned post-surgery radiotherapy
  • No history of allergy to study drug components, severe hypersensitivity reaction to any monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSS tumors)
  • No intercurrent illnesses, including but not limited to infections, unstable angina pectoris
  • No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection
  • No autoimmune disease
  • No conditions requiring systemic treatment with either corticosteroids (10 mg daily prednisone or more and equivalents) or other immunosuppressive medications within 14 days of study drug administration
  • No live vaccines in the 4 weeks prior to inclusion

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Relatlimab cohort 5 (pMMR/MSS tumors)
drug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: BMS-986016
Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29, in cohort 7 160mg on day 1, day 29 and day 57
Other Names:
  • Relatlimab
Experimental: group 1 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
  • Ipilimumab (Yervoy)
Experimental: group 2 - closed
drug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV) drug: celecoxib 200 mg daily (oral)
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: Ipilimumab
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
Other Names:
  • Ipilimumab (Yervoy)
Drug: Celecoxib 200mg
celecoxib will be administered starting day 1 until 1 day before surgery daily (if patient is randomized to group 2 (only applicable for patients with a MSS tumor)
Other Names:
  • Celebrex
Experimental: Anti-IL8 cohort 4 (pMMR/MSS tumors) - closed
drug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: BMS-986253
BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
Other Names:
  • Anti-IL8
Experimental: Relatlimab cohort 6 (dMMR/MSI tumors) - closed
drug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: BMS-986016
Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29, in cohort 7 160mg on day 1, day 29 and day 57
Other Names:
  • Relatlimab
Experimental: Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab
Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) + relatlimab (160mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)
Drug: BMS-986016
Relatlimab will be administered IV, in cohort 5 240mg on day 1 and day 15, in cohort 6 480mg on day 1 and day 29, in cohort 7 160mg on day 1, day 29 and day 57
Other Names:
  • Relatlimab
Experimental: Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab - closed
Patients with dMMR tumors will be treated with 3 cycles of neoadjuvant nivolumab (480mg) on day 1, day 29 and day 57 followed by surgery within 12 weeks and not earlier than 10 weeks from enrollment.
Drug: Nivolumab
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Other Names:
  • nivolumab (opdivo)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of adverse events during the treatment and follow-up (safety)
Time Frame: until 100 days after last patient last study drug treatment
Adverse events will be assessed (according to CTCAE v4.0) during treatment and follow-up.
until 100 days after last patient last study drug treatment
Disease free survival
Time Frame: until 5 years after diagnosis
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
until 5 years after diagnosis
Major Pathological Response
Time Frame: From date of randomization until the date of first documented progression, assessed up to 63 months
To assess efficacy of neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab plus relatlimab in terms of major pathologic response
From date of randomization until the date of first documented progression, assessed up to 63 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Immune activating capacity of short-term pre-operative immunotherapy
Time Frame: within 2 years after study completion
identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies
within 2 years after study completion
Relapse free survival
Time Frame: 3-5 years after last patient inclusion.
3-5 years after last patient inclusion.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Netherlands Cancer Institute

Collaborators

Bristol-Myers Squibb

Investigators

  • Principal Investigator: Myriam Chalabi, MD, Antoni van Leeuwenhoek

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 29, 2017

Primary Completion (Estimated)

March 1, 2032

Study Completion (Estimated)

March 1, 2032

Study Registration Dates

First Submitted

December 15, 2016

First Submitted That Met QC Criteria

January 19, 2017

First Posted (Estimated)

January 20, 2017

Study Record Updates

Last Update Posted (Actual)

March 5, 2026

Last Update Submitted That Met QC Criteria

March 3, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N16NCI
  • 2024-513314-35-00 (Ctis)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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