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

ConditionColon Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorThe Netherlands Cancer Institute

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Nivolumab

    Drug

    Nivolumab 3mg/kg (day 1 and day 15), administered neoadjuvant before surgery

  • Ipilimumab

    Drug

    Ipilimumab 1 mg/kg (day 1) ,administered neoadjuvant before surgery

  • Celecoxib 200mg

    Drug

    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

    Drug

    BMS-986253 2400mg IV will be administered on day 1 and 15 (only applicable for patients with MSS tumors)

  • Relatlimab (BMS-986016)

    Drug

    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

Treatment groups

353 Participants
are divided into 7 treatment groups

7

Treatment groups

See each treatment group below.

Group A: group 1 - closedExperimental treatment 2 interventions
Group B: group 2 - closedExperimental treatment 3 interventions
Group C: Anti-IL8 cohort 4 (pMMR/MSS tumors) - closedExperimental treatment 2 interventions
Group D: Relatlimab cohort 5 (pMMR/MSS tumors)Experimental treatment 2 interventions
Group E: Relatlimab cohort 6 (dMMR/MSI tumors) - closedExperimental treatment 2 interventions
Group F: Cohort 7 - dMMR - 3 cycles neoadjuvant nivolumab + relatlimab - closedExperimental treatment 2 interventions
Group G: Cohort 8 - dMMR - 3 cycles neoadjuvant nivolumab - closedExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
until 100 days after last patient last study drug treatment
2

Disease free survival

To assess efficacy of neoadjuvant ipilimumab plus nivolumab in terms of disease-free survival

Time frame
until 5 years after diagnosis
3

Major Pathological Response

To assess efficacy of neoadjuvant nivolumab monotherapy and neoadjuvant nivolumab plus relatlimab in terms of major pathologic response

Time frame
From date of randomization until the date of first documented progression, assessed up to 63 months

Secondary outcomes

1

Immune activating capacity of short-term pre-operative immunotherapy

identify underlying potential escape mechanisms by comparing pre-treatment and post-treatment biopsies

Time frame
within 2 years after study completion
2

Relapse free survival

Time frame
3-5 years after last patient inclusion.

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

The Netherlands Cancer Institute

Lead sponsor

Bristol-Myers Squibb

Collaborator

Source ClinicalTrials.gov
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