Metastatic Colorectal CancerPhase 2NIPIRESCUENCT05310643
Nivolumab and Ipilimumab in Anti-PD1-Resistant dMMR/MSI mCRC
A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 9 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Nivolumab and Ipilimumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 9 sitesFrance
- Study dates
- 5 May 2022to Sep 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed and dated patient informed consent form and willingness to comply with all study procedures and availability for the study duration,
- Age ≥ 18 years,
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, and 2,
- Histologically confirmed colorectal adenocarcinoma,
- Documented metastatic disease not suitable for complete surgical resection,
- 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
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- 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,
- 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,
- 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.
- NB: Agreement of the Sponsor (GERCOR) is mandatory to include the patient (the patient's file will be verified to confirm MSI/dMMR status before inclusion [an anonymized fax] and confirmation of a patient's allocation will be sent by mail to the Investigator within 24h).
- For all patients, a new biopsy must be performed to obtain fresh anti-PD1 resistant tumor tissue prior to study treatment initiation,
- For all patients, archival formalin-fixed paraffin-embedded tissue (FFPE) blocks and/or FFPE unstained slides (minimum of 30 positively charged slides representative of tumor tissue and non-tumor adjacent prior to anti-PD1 therapy (i.e., primary or metastatic site naïve of immunotherapy) must be submitted to the central laboratory,
- Adequate hematologic and end-organ function, defined by the following laboratory test results, obtained within 7 days prior inclusion: - Adequate hematological status (White blood cell > 2000/μL; o Neutrophils > 1500/μL; Platelets > 100.000/μL; Hemoglobin > 10.0 g/dL; - Adequate renal function: Serum creatinine level < 120 μM; Clearance > 50 ml/min (Modification of the Diet in Renal Disease [MDRD] or Cockcroft and Gault, - Adequate liver function: Serum bilirubin ≤ 1.5 x upper normal limit (ULN); Alkaline phosphatase (ALP) ≤ 3.0 x ULN; Alanine aminotransferase (ALT) ≤ 3.0 x ULN; Aspartate aminotransferase (AST) ≤ 3.0 x ULN; Hemostasis: Prothrombin time (PT)/International normalized ratio (INR) and activated partial PT (aPTT) ≤ 1.5 x ULN unless participants are receiving anticoagulant therapy and their INR is stable and within the recommended range for the desired level of anticoagulation,
- Females of childbearing potential must have negative serum pregnancy test within 7 days before starting study treatment,
- Women of childbearing potential should use effective contraception during treatment and at least 5 months thereafter.
- Registration in a national health care system (Protection Universelle Maladie [PUMa] included)
Who cannot join
- Known brain metastases or leptomeningeal metastases,
- 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),
- Discontinuation of anti-PD1 treatment due to treatment-related adverse event (AE) grade > 2 (NCI CTCAE v 5.0),
- 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,
- Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, radiotherapy, immunotherapy),
- Major surgical procedure within 4 weeks prior to initiation of study treatment,
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- Patients receiving any investigational drug, biological, immunological therapy within the previous 21 days before study treatment,
- 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,
- History of interstitial lung disease or pneumonitis,
- 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.
- NB : Exceptions to this criterion: - Inhaled or topical steroids, and adrenal replacement steroid doses >10 mg daily prednisone or equivalent are permitted in the absence of active autoimmune disease, - Systemic corticosteroids at physiologic doses not exceeding strictly 10 mg/day of prednisone or its equivalent,
- Prior malignancy active within the previous 3 years, except for: - Locally curable cancers that have been apparently cured (e.g. squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast), - Lynch syndrome-related non-colorectal cancer in complete remission for > 1 year,
- Active hepatitis B (defined as having a positive hepatitis B surface antigen [HBsAg] test prior to randomization) virus (HBV) or hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection. Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive antibody to hepatitis B core antigen antibody test) are eligible. Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid.
- Prior allogeneic bone marrow transplantation or prior solid organ transplantation,
- Any serious or uncontrolled medical disorder that, in the opinion of Investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the participant to receive protocol therapy, or interfere with the interpretation of study results,
- Known allergy/hypersensitivity to any component of study agents,
- Administration of a (attenuated) live vaccine within 28 days of planned start of study therapy of known need for this vaccine during treatment,
- Patient under a legal protection regime (guardianship, curatorship, judicial safeguard) or administrative decision or incapable of giving his/her consent,
- Impossibility of submitting to the medical follow-up of the study for geographical, social, or psychiatric illness.
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
France9 sites, 9 recruiting
- Recruiting
CHU Jean Minjoz
Besançon
Angélique VIENOT, MD
Angélique VIENOT, MD
- Recruiting
Institute Bergonie
Bordeaux
Lola Jade PALMIERI, MD
- Recruiting
CHRU Lille
Lille
Anthony TURPIN, MD
Anthony TURPIN, MD
- Recruiting
CHU Dupuytren
Limoges
Frédéric THUILLIER, MD
- Recruiting
Centre Léon Bérard
Lyon
Clélia COUTZAC, MD
Christelle De la Fouchardière, MD
- Recruiting
ICM Val d'Aurelle
Montpellier
Thibault MAZARD, MD
Thibault MAZARD, MD
- Recruiting
Centre Antoine Lacassagne
Nice
Ludovic EVESQUE, MD
- Recruiting
Hôpital Saint Antoine
Paris
Romain COHEN, MD
Romain COHEN, MD
- Recruiting
CHU Poitiers
Poitiers
David TOUGERON, MD
David TOUGERON, MD
About this study
Official title: 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)
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.
Read the 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.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Nivolumab, Ipilimumab
- Keywords
- dMMR, MSI
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
Induction therapy with nivolumab 240 mg; 4 infusions, every 3 weeks.
Maintenance therapy with nivolumab 480 mg; 21 infusions, every 4 weeks.
IpilimumabDrug
Also called Yervoy
Induction therapy with ipilimumab 1 mg/kg; 4 infusions, every 3 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Treatment phase | Experimental | Induction therapy: Nivolumab 240 mg + ipilimumab 1 mg/kg every 3 weeks for 4 dosing cycles (4 infusions of nivolumab and ipilimumab).
Maintenance therapy: Nivolumab 480 mg every 4 weeks (21 infusions). Receives: Drug: Nivolumab; Drug: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response rate (ORR) by RECIST 1.1
ORR defined as the number of patients with partial or complete response from the beginning of the treatment divided by the total of number of patients evaluable for the primary endpoint analysis.
Measured: At week 24 (6 months)
Secondary outcomes (5)
Number of participants with treatment-related adverse events
All grade and severe toxicities, according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0.
Measured: Up to 100 days after the last dose
Disease control rate (DCR)
DCR by RECIST 1.1 is defined as the percentage of patients who achieve complete response, partial response, or stable disease after study treatment.
Measured: At 24 week
Duration of response
Duration of response is measured from the time of the first response observed (partial or complete) until documented tumor progression or death.
Measured: From the time of the first response observed (PR or CR) until documented tumor progression or death, assessed up to 3 years from inclusion
Progression-free survival (PFS)
PFS by RECIST 1.1 is defined as time from beginning of treatment to progression or death due to any cause, whichever occurs first. Death event will be assessed until the initiation of the subsequent anti-cancer therapy.
Measured: From beginning of treatment to progression or death due to any cause, whichever occurs first, assessed up to 3 years from inclusion
Overall survival (OS)
OS is defined as the time between beginning of treatment and death from any cause. Survival data will be censored at the last follow-up.
Measured: From beginning of treatment to death from any cause, assessed up to 3 years from inclusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Apr 2022
- Study start5 May 2022
- Primary completionSep 2025 (estimated)
- Study completionSep 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- GERCOR - Multidisciplinary Oncology Cooperative Group
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Romain COHEN, MD, Principal investigator, Saint Antoine Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05310643
- Sponsor's protocol ID
- NIPIRESCUE G-113
- Acronym
- NIPIRESCUE
- Status last verified
- Jun 2025
- First submitted
- 28 Jan 2022
- Last updated
- 1 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05310643
- Acronym / sponsor ID
- NIPIRESCUE / NIPIRESCUE G-113
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- dMMR, MSI
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- GERCOR - Multidisciplinary Oncology Cooperative GroupUniversity, hospital or other
- Study start
- 5 May 2022 (actual)
- Primary completion
- Sep 2025 (estimated)
- Study completion
- Sep 2027 (estimated)
- First posted
- 5 Apr 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment phase | Experimental | Drug: Nivolumab, Drug: IpilimumabInduction therapy: Nivolumab 240 mg + ipilimumab 1 mg/kg every 3 weeks for 4 dosing cycles (4 infusions of nivolumab and ipilimumab). Maintenance therapy: Nivolumab 480 mg every 4 weeks (21 infusions). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Signed and dated patient informed consent form and willingness to comply with all study procedures and availability for the study duration,
- Age ≥ 18 years,
- Eastern Cooperative Oncology Group performance status (ECOG PS) of 0, 1, and 2,
- Histologically confirmed colorectal adenocarcinoma,
- Documented metastatic disease not suitable for complete surgical resection,
Key exclusion criteria (19 listed)
- Known brain metastases or leptomeningeal metastases,
- 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),
- Discontinuation of anti-PD1 treatment due to treatment-related adverse event (AE) grade > 2 (NCI CTCAE v 5.0),
- 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,
- Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, radiotherapy, immunotherapy),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoInduction therapy with nivolumab 240 mg; 4 infusions, every 3 weeks. Maintenance therapy with nivolumab 480 mg; 21 infusions, every 4 weeks. | Drug | Treatment phase |
| IpilimumabAlso: YervoyInduction therapy with ipilimumab 1 mg/kg; 4 infusions, every 3 weeks. | Drug | Treatment phase |
Primary outcome
Objective response rate (ORR) by RECIST 1.1
Time frame: At week 24 (6 months)
ORR defined as the number of patients with partial or complete response from the beginning of the treatment divided by the total of number of patients evaluable for the primary endpoint analysis.
5 secondary outcomes
Number of participants with treatment-related adverse events
Time frame: Up to 100 days after the last dose
Disease control rate (DCR)
Time frame: At 24 week
Duration of response
Time frame: From the time of the first response observed (PR or CR) until documented tumor progression or death, assessed up to 3 years from inclusion
Progression-free survival (PFS)
Time frame: From beginning of treatment to progression or death due to any cause, whichever occurs first, assessed up to 3 years from inclusion
Overall survival (OS)
Time frame: From beginning of treatment to death from any cause, assessed up to 3 years from inclusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2025.
- Individual participant dataSharing planned: No
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CRC
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Romain COHEN, MD principal investigator
Saint Antoine Hospital
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nivolumab and Ipilimumab in people with Metastatic Colorectal Cancer, run by GERCOR - Multidisciplinary Oncology Cooperative Group at 9 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 17 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 1 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marie Line GARCIA LARNICOL, MD (01 40 29 85 00, marie-line.garcia-larnicol@gercor.com.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response rate (ORR) by RECIST 1.1 (time frame: At week 24 (6 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Jul 2025.