NCT03026140

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

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)

• Status: Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 353 (estimated)
• Sponsor: The Netherlands Cancer Institute · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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).

Conditions

• Colon Carcinoma

Interventions

Type	Name	Description
DRUG	Nivolumab	Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery
DRUG	Ipilimumab	Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery
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)
DRUG	BMS-986253	BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)
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

Timeline

• Start date: 2017-03-29
• Primary completion: 2032-03-01
• Completion: 2032-03-01
• First posted: 2017-01-20
• Last updated: 2026-03-05

Locations

6 sites across 1 country: Netherlands