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

Last updated: March 3, 2026
Sponsor: The Netherlands Cancer Institute
Overall Status: Active - Recruiting

Phase

2

Condition

Colon Cancer

Colorectal Cancer

Colon Cancer; Rectal Cancer

Treatment

BMS-986016

Celecoxib 200mg

Nivolumab

Clinical Study ID

NCT03026140
N16NCI
2024-513314-35-00
  • Ages > 18
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion criteria:

  • Signed written informed consent

  • Patients at least 18 years of age

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

  • No signs of distant metastases on CT-scan and physical examination;

  • dMMR cohorts 3+6: >cT3 and/or N+

Exclusion

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 orPD-L1

  • For patients with MSS tumors: no current use of NSAIDs or COX2-inhibitors atregistration and no active peptic ulcer, gastrointestinal bleeding, unstableischemic heart disease of thrombus etiology or significant established ischemicheart 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 toany monoclonal antibody, allergy or severe hypersensitivity to NSAIDs or COX2-I (MSStumors)

  • No intercurrent illnesses, including but not limited to infections, unstable anginapectoris

  • No positive test for hepatitis B virus surface antigen (HBsAg) or hepatitis C virusribonucleic acid (HCV antibody) indicating acute or chronic infection

  • No autoimmune disease

  • No conditions requiring systemic treatment with either corticosteroids (10 mg dailyprednisone or more and equivalents) or other immunosuppressive medications within 14days of study drug administration

  • No live vaccines in the 4 weeks prior to inclusion

Study Design

Total Participants: 353
Treatment Group(s): 5
Primary Treatment: BMS-986016
Phase: 2
Study Start date:
March 29, 2017
Estimated Completion Date:
March 01, 2032

Study 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).

Connect with a study center

  • Marieke van de Belt

    Amsterdam, 1066CX
    Netherlands

    Active - Recruiting

  • OLVG

    Amsterdam,
    Netherlands

    Active - Recruiting

  • Marieke van de Belt

    Amsterdam 2759794, 1066CX
    Netherlands

    Active - Recruiting

  • OLVG

    Amsterdam 2759794,
    Netherlands

    Site Not Available

  • Amphia ziekenhuis

    Breda,
    Netherlands

    Site Not Available

  • Haga ziekenhuis

    Den Haag,
    Netherlands

    Site Not Available

  • Catharina Ziekenhuis

    Eindhoven,
    Netherlands

    Active - Recruiting

  • Catharina Ziekenhuis

    Eindhoven 2756253,
    Netherlands

    Site Not Available

  • Spaarne Ziekenhuis

    Haarlem,
    Netherlands

    Active - Recruiting

  • Spaarne Ziekenhuis

    Haarlem 2755003,
    Netherlands

    Site Not Available

  • Tergooi

    Hilversum,
    Netherlands

    Site Not Available

  • Tergooi

    Hilversum 2754064,
    Netherlands

    Site Not Available

  • Haga ziekenhuis

    The Hague,
    Netherlands

    Site Not Available

  • Haga ziekenhuis

    The Hague 2747373,
    Netherlands

    Site Not Available

Map preview placeholder

Not the study for you?

Let us help you find the best match. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.