Neoadjuvant Immune Checkpoint Inhibition and Novel IO Combinations in Early-stage Colon Cancer
NICHE
2 other identifiers
interventional
353
1 country
6
Brief 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Mar 2017
Longer than P75 for phase_2
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
December 15, 2016
CompletedFirst Posted
Study publicly available on registry
January 20, 2017
CompletedStudy Start
First participant enrolled
March 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2032
ExpectedStudy Completion
Last participant's last visit for all outcomes
March 1, 2032
March 5, 2026
March 1, 2026
14.9 years
December 15, 2016
March 3, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
Incidence of adverse events during the treatment and follow-up (safety)
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
To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival
until 5 years after diagnosis
Major Pathological Response
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 Outcomes (2)
Immune activating capacity of short-term pre-operative immunotherapy
within 2 years after study completion
Relapse free survival
3-5 years after last patient inclusion.
Study Arms (7)
group 1 - closed
EXPERIMENTALdrug: ipilimumab 1 mg/kg day 1 (IV) drug: nivolumab 3 mg/kg on day 1 and day 15 (IV)
group 2 - closed
EXPERIMENTALdrug: 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)
Anti-IL8 cohort 4 (pMMR/MSS tumors) - closed
EXPERIMENTALdrug: nivolumab 3 mg/kg day 1 and day 15 (IV) drug: BMS-986253 (anti-IL8) 2400mg on day 1 and day 15 (IV)
Relatlimab cohort 5 (pMMR/MSS tumors)
EXPERIMENTALdrug: nivolumab 240mg IV on day 1 and day 15 drug: relatlimab 240mg IV on day 1 and day 15
Relatlimab cohort 6 (dMMR/MSI tumors) - closed
EXPERIMENTALdrug: nivolumab 480mg IV on day 1 and day 29 drug: relatlimab 480mg IV on day 1 and day 29
Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab
EXPERIMENTALPatients 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
Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab - closed
EXPERIMENTALPatients 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.
Interventions
Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
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)
BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
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
Eligibility Criteria
You may qualify if:
- 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+
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- The Netherlands Cancer Institutelead
- Bristol-Myers Squibbcollaborator
Study Sites (6)
Marieke van de Belt
Amsterdam, 1066CX, Netherlands
OLVG
Amsterdam, Netherlands
Catharina Ziekenhuis
Eindhoven, Netherlands
Spaarne Ziekenhuis
Haarlem, Netherlands
Tergooi
Hilversum, Netherlands
Haga ziekenhuis
The Hague, Netherlands
Related Publications (6)
Tan PB, Verschoor YL, van den Berg JG, Balduzzi S, Kok NFM, Ijsselsteijn ME, Moore K, Jurdi A, Tin A, Kaptein P, van Leerdam ME, Haanen JBAG, Voest EE, de Miranda NFCC, Schumacher TN, Wessels LFA, Chalabi M. Neoadjuvant immunotherapy in mismatch-repair-proficient colon cancers. Nature. 2025 Dec;648(8094):726-735. doi: 10.1038/s41586-025-09679-4. Epub 2025 Oct 20.
PMID: 41115454DERIVEDde Gooyer PGM, Verschoor YL, van den Dungen LDW, Balduzzi S, Marsman HA, Geukes Foppen MH, Grootscholten C, Dokter S, den Hartog AG, Verbeek WHM, Woensdregt K, van den Broek JJ, Oosterling SJ, Schumacher TN, Kuhlmann KFD, Beets-Tan RGH, Haanen JBAG, van Leerdam ME, van den Berg JG, Chalabi M. Neoadjuvant nivolumab and relatlimab in locally advanced MMR-deficient colon cancer: a phase 2 trial. Nat Med. 2024 Nov;30(11):3284-3290. doi: 10.1038/s41591-024-03250-w. Epub 2024 Sep 15.
PMID: 39278994DERIVEDCercek A. Neoadjuvant Treatment of Mismatch Repair-Deficient Colon Cancer - Clinically Meaningful? N Engl J Med. 2024 Jun 6;390(21):2024-2025. doi: 10.1056/NEJMe2404601. No abstract available.
PMID: 38838316DERIVEDChalabi M, Verschoor YL, Tan PB, Balduzzi S, Van Lent AU, Grootscholten C, Dokter S, Buller NV, Grotenhuis BA, Kuhlmann K, Burger JW, Huibregtse IL, Aukema TS, Hendriks ER, Oosterling SJ, Snaebjornsson P, Voest EE, Wessels LF, Beets-Tan RG, Van Leerdam ME, Schumacher TN, van den Berg JG, Beets GL, Haanen JB. Neoadjuvant Immunotherapy in Locally Advanced Mismatch Repair-Deficient Colon Cancer. N Engl J Med. 2024 Jun 6;390(21):1949-1958. doi: 10.1056/NEJMoa2400634.
PMID: 38838311DERIVEDWang D, Cabalag CS, Clemons NJ, DuBois RN. Cyclooxygenases and Prostaglandins in Tumor Immunology and Microenvironment of Gastrointestinal Cancer. Gastroenterology. 2021 Dec;161(6):1813-1829. doi: 10.1053/j.gastro.2021.09.059. Epub 2021 Oct 2.
PMID: 34606846DERIVEDChalabi M, Fanchi LF, Dijkstra KK, Van den Berg JG, Aalbers AG, Sikorska K, Lopez-Yurda M, Grootscholten C, Beets GL, Snaebjornsson P, Maas M, Mertz M, Veninga V, Bounova G, Broeks A, Beets-Tan RG, de Wijkerslooth TR, van Lent AU, Marsman HA, Nuijten E, Kok NF, Kuiper M, Verbeek WH, Kok M, Van Leerdam ME, Schumacher TN, Voest EE, Haanen JB. Neoadjuvant immunotherapy leads to pathological responses in MMR-proficient and MMR-deficient early-stage colon cancers. Nat Med. 2020 Apr;26(4):566-576. doi: 10.1038/s41591-020-0805-8. Epub 2020 Apr 6.
PMID: 32251400DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Myriam Chalabi, MD
Antoni van Leeuwenhoek
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
December 15, 2016
First Posted
January 20, 2017
Study Start
March 29, 2017
Primary Completion (Estimated)
March 1, 2032
Study Completion (Estimated)
March 1, 2032
Last Updated
March 5, 2026
Record last verified: 2026-03
Data Sharing
- IPD Sharing
- Will not share