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RECRUITINGPHASE2

Nivolumab and Ipilimumab in Anti-PD1-Resistant dMMR/MSI mCRC

Nivolumab and Ipilimumab in Patients With dMMR and/or MSI Metastatic Colorectal Cancer Resistant to Anti-PD1 Monotherapy: An Open-label Phase II GERCOR Trial (NIPIRESCUE)

NCT05310643•GERCOR - Multidisciplinary Oncology Cooperative Group

View on ClinicalTrials.gov

Summary

NIPIRESCUE evaluates nivolumab and ipilimumab in patients with MSI/dMMR mCRC resistant to anti-PD1 monotherapy and previously treated with fluoropyrimidine, oxaliplatine, irinotecan, and anti- vascular endothelial growth factor (VEGF) or anti- epidermal growth factor receptor (EGFR) therapy.

Detailed Description

NIPIRESCUE is a national, single-arm, open-label phase II study, evaluating nivolumab and ipilimumab in patients with MSI/dMMR mCRC resistant to anti-PD1 monotherapy and previously treated with fluoropyrimidine, oxaliplatine, irinotecan, and VEGF or anti-EGFR therapy. Patients after inclusion will receive: Induction therapy with nivolumab 240 mg and ipilimumab 1 mg/kg every 3 weeks for 4 dosing cycles (4 infusions of nivolumab and ipilimumab) and maintenance therapy with by nivolumab 480 mg every 4 weeks (21 infusions). The primary endpoint is ORR at 24 weeks (6 months) from the beginning of the treatment evaluated by RECIST 1.1.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•1. Signed and dated patient informed consent form and willingness to comply with all study procedures and availability for the study duration,
•2. Age ≥ 18 years,
•3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, and 2,
•4. Histologically confirmed colorectal adenocarcinoma,
•5. Documented metastatic disease not suitable for complete surgical resection,
•6. Disease progression per iRECIST criteria (i.e., iCPD: immune confirmed PD) during monotherapy with anti-PD1 monoclonal antibody or less than 6 months after the discontinuation of anti-PD1 monoclonal antibody
•7. Disease progression during, after, or patients who are intolerant or have contraindications to approved standard therapies for the metastatic disease, which must include at least: • Fluoropyrimidine, oxaliplatin, and irinotecan, • Anti-EGFR therapy if wild-type RAS, • Anti-VEGF therapy,
•8. At least one measurable lesion as assessed by CT-scan or magnetic resonance imaging (MRI) according to RECIST 1.1 and feasibility of repeated radiological assessments,
•9. dMMR and/or MSI tumor status defined by: - Loss of MMR protein expression using immunohistochemistry with four (anti-MLH1, anti-MSH2, anti-MSH6, and anti-PMS2) antibodies, - and/or ≥ two unstable markers by pentaplex polymerase chain reaction (BAT-25, BAT-26, NR-21, NR-24, and NR-27), NB: In case of loss of expression of only one MMR protein immunohistochemistry, it is necessary to confirm the tumor is MSI using pentaplex PCR.
•NB: In cases with two unstable markers, comparison with matching normal tissue is required.
+7 more criteria

Exclusion Criteria

•1. Known brain metastases or leptomeningeal metastases,
•2. Persistence of toxicities related to prior treatments (chemotherapies or anti-P1 therapies) grade \> 1 (NCI CTCAE v 5.0; except dysthyroidism, adrenal gland deficiency, alopecia, fatigue or oxaliplatin-induced peripheral sensory neuropathy which can be ≥ grade 2),
•3. Discontinuation of anti-PD1 treatment due to treatment-related adverse event (AE) grade \> 2 (NCI CTCAE v 5.0),
•4. Prior treatment with an anti-LAG-3, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immuno-stimulatory antitumor agents, except anti-PD1 antibodies,
•5. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, radiotherapy, immunotherapy),
•6. Major surgical procedure within 4 weeks prior to initiation of study treatment,
•7. Patients receiving any investigational drug, biological, immunological therapy within the previous 21 days before study treatment,
•8. Patients with an active, known, or suspected autoimmune disease. Patients with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to be enrolled,
•9. History of interstitial lung disease or pneumonitis,
•10. Patients with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone or equivalent) or other immunosuppressive medications within 14 days of inclusion.
+9 more criteria

Locations (9)

CHU Jean Minjoz

Besançon, France

Institute Bergonie

Bordeaux, France

CHRU Lille

Lille, France

CHU Dupuytren

Limoges, France

Centre Léon Bérard

Lyon, France

ICM Val d'Aurelle

Montpellier, France

Centre Antoine Lacassagne

Nice, France

Hôpital Saint Antoine

Paris, France

CHU Poitiers

Poitiers, France

Key Dates

Start Date

May 5, 2022

Primary Completion Date

September 1, 2025

Completion Date

September 1, 2027

Last Updated

July 1, 2025

Enrollment

ESTIMATED participants

Conditions

Metastatic Colorectal Cancer

Interventions

Nivolumab

DRUG

Ipilimumab

DRUG

Contacts

Marie Line GARCIA LARNICOL, MD

CONTACT

01 40 29 85 00 marie-line.garcia-larnicol@gercor.com.fr

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: July 1, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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Nivolumab and Ipilimumab in Anti-PD1-Resistant dMMR/MSI mCRC

Inclusion Criteria

Exclusion Criteria

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