Metastatic Colorectal CancerPhase 2COLIBRI-GINCT07359456
Testing Ivonescimab in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancers Without Liver Metastases
A Phase 2 study testing Ivonescimab, Bevacizumab and FOLFIRI Protocol in people with Metastatic Colorectal Cancer, run by UNICANCER at 22 sites in France.
Trial summary
The goal of this clinical trial is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of PFS. 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?
- Ivonescimab, Bevacizumab and FOLFIRI Protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- 22 sitesFrance
- Study dates
- 31 Aug 2026to Aug 2033
- 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 a written informed consent form prior to any trial specific procedures. Note: If the patient is physically unable to provide their written consent, a trusted person of their choice, independent of the Investigator or the Sponsor, can confirm the patients consent in writing.
- Histologically confirmed diagnosis of non resectable pMMR (by IHC) and MSS (by molecular biology) and BRAFwt metastatic colorectal cancer with no liver metastasis.
- Must have previously received 1st-line treatment with FOLFOX +/- anti-VEGF (Vascular endothelial growth factor) or EGFR (Epithelial Growth Factor Receptor) therapy (including recurrence within 6 months after adjuvant FOLFOX for localized CRC and adjuvant/perioperative FOLFOX for mCRC, as well as progressive disease under maintenance treatment for mCRC) OR 1st-line treatment with FOLFIRINOX (Oxaliplatin, Irinotecan, 5FU, Folinic acid) (under the following condition: no progression under triplet-chemotherapy, progression under LV5FU2 (Folinic acid + 5FU) maintenance, irinotecan stopped for at least 3 months for a reason other than progression)
- Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Age ≥18 years.
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- Adequate Organ Function:
- Hematology (no blood transfusions or growth factor therapy used within 7 days of the screening):
- Absolute neutrophil count (ANC) ≥ 1.5 × 109/L
- Platelet count ≥ 100 × 109/L
- Hemoglobin ≥ 10.0 g/dL
- Kidneys:
- Creatinine clearance ≥ 50 mL/min using the Cockcroft-Gault formula or estimated glomerular filtration rate (eGFR) value ≥50 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation
- Urine protein < 2+ or 24 hour urine protein quantification < 1.0 g
- Liver:
- Serum total bilirubin ≤ 1.5 × upper limit of normal (ULN)
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN
- Coagulation: prothrombin time (PT) or international normalized ratio (INR) ≤ 1.5 x ULN, and partial prothrombin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 × ULN (unless abnormalities are unrelated to coagulopathy, or prophylactic coagulation)
- Life expectancy ≥ 3 months
- Women of childbearing potential (WOCBP) having sex with an unsterilized male partner and unsterilized males having sex with a female partner of childbearing potential, must agree to use an effective method of contraception for the duration of trial participation and as required after completing study treatment (9 months after the last dose of trial treatment). Men must also agree to not donate sperm and women must agree to not donate oocytes during the specified period.
- WOCBP must have a negative serum pregnancy test performed within 3 days before inclusion and a negative urine pregnancy test on the day of first dose, prior to treatment administration.
- Willing and able to comply with the protocol for the duration of the study including scheduled visits, treatment plan, laboratory tests, and other study procedures
- Affiliation to the Social Security System (or equivalent)
Who cannot join
- Presence of liver metastases by CT-scan or MRI. Note: Patients with prior definitively treated liver metastases (surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy) are eligible if no evidence of metastatic disease in the liver on subsequent imaging).
- History of Gilbert's syndrome
- Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin or in situ tumour treated by surgery).
- Patients with high microsatellite instability (MSI-H), mismatched repair disease (dMMR) and/or BRAF V600E mutated tumor.
- Toxicities from previous treatment not resolved to grade ≤ 1 (according to the version 5.0 of the National Cancer Institute - Common terminology criteria for adverse events [NCI-CTCAE v5.0]) before treatment start with the exception of alopecia.
- Major surgical procedures or serious trauma within 4 weeks prior to randomization, or plans for major surgical procedures within 4 weeks after the first dose (as determined by the investigator). Minor local procedures (excluding central venous catheterization and port implantation) within 3 days prior to randomization.
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- History of bleeding tendencies or coagulopathy and/or clinically significant bleeding symptoms or risk within 4 weeks prior to randomization, including but not limited to:
- Clinically significant GI bleeding such as hematochezia or any episodes of melena or documented acute hemoglobin drop of more than 1 gm in 2 weeks prior to randomization
- Current use of prophylactic or full-dose anticoagulants or anti-platelet agents for therapeutic purposes that is not stable prior to randomization is not allowed. The use of full-dose anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits according to the medical standard of the enrolling institution.
- Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy
- History of major diseases before randomization, specifically:
- Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association (NYHA) classification ≥ grade 2) or vascular disease (eg, aortic aneurysm at risk of rupture) that required hospitalization within 12 months prior to randomization, or other cardiac impairment that may affect the safety evaluation of the study drug (eg, poorly controlled arrhythmias, myocardial ischemia)
- History of oesophageal gastric varices, severe ulcers, wounds that do not heal, abdominal fistula, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months before randomization
- History of arterial thromboembolic event, venous thromboembolic event of Grade 3 and above as specified in National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to randomization
- Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks before randomization
- History of perforation of the gastrointestinal tract and/or fistula, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection) within 6 months prior to randomization
- Current presence of significant radiographic or clinical manifestations of gastrointestinal (GI) obstruction.
- Ascites requiring paracentesis within last 30 days
- Symptomatic central nervous system (CNS) metastases or leptomeningeal disease Note: Asymptomatic patients (previously treated or untreated) in the absence of corticosteroid and anti-epileptic therapy are allowed. CNS metastases must be stable for ≥4 weeks prior to randomization.
- Presence of brainstem, meningeal metastases, spinal cord metastases, or compression.
- Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
- Prior immunosuppressive therapy: immunosuppressive doses of systemic medications of > 10 mg/day of prednisone or equivalent must be discontinued ≥ 2 weeks before the first dose of study treatment. Short courses of high dose corticosteroids and/or continuous low dose of prednisone (< 10 mg/day) are permitted. In addition, inhaled, intranasal, intraocular, and/or joint injections of corticosteroids are allowed.
- Any prior clinically significant or active autoimmune disease requiring systemic therapy (eg, with disease- modifying drugs, prednisone >10 mg daily or equivalent, immunosuppressant therapy or immunomodulatory agents [eg, infliximab or IVIG (intravenous immunoglobulin)]) within 2 years prior to randomization; however, the following will be allowed:
- o Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is permitted.
- Known history of, or any evidence of, interstitial lung disease.
- Patient with non-controlled human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) infection (patient with undetectable viral load (HIV RNA PCR) and CD4 (T CD4 lymphocytes) above 350 either spontaneously or on stable anti-viral regimen).
- Known human immunodeficiency virus infection with CD4+ T cell counts < 350 cells/µL, hepatitis C infection (subjects with hepatitis C who achieve a sustained virologic response following antiviral therapy are permitted), or hepatitis B infection (subjects with hepatitis B surface antigen or core antibody who achieve sustained virologic response with antiviral therapy directed at hepatitis B are permitted)
- Proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).
- Known history of hypersensitivity to ivonescimab and to one of the study drugs or one of its excipients
- Any condition which in the Investigator's opinion makes it undesirable for the subject to participate in the trial or which would jeopardize compliance with the protocol.
- Pregnant or breast-feeding females.
- Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable.
- Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
- Individuals deprived of liberty or placed under protective custody or guardianship.
Trial locations and contacts
22 sites in 1 country. Contact the study team or a site near you to ask about taking part.
22 sites in 1 country
France22 sites
CH d'Auxerre
Auxerre
Anne-Laure VILLING, MD
Centre Hospitalier de Beuvry
Beuvry
Hélène VAN DAMME, MD
Centre François Baclesse
Caen
Aurélie PARZY, MD, a.parzy@baclesse.unicancer.fr
CH de Calais
Calais
Nathalie IBRAHIM, MD
Polyclinique Saint Côme
Compiègne
Kaïs ALDABBAGH, MD
Institut Andrée Dutreix
Coudekerque-Branche
Jean-Baptiste AISENFARB, MD
Centre Oscar Lambret
Lille
Aurélien CARNOT, MD, a-carnot@o-lambret.fr
Centre Léon Bérard
Lyon
Clélia COUTZAC, MD
Hôpital Européen de Marseille
Marseille
Nicolas BARRIERE, MD
Hôpital la Timone
Marseille
Laetitia DAHAN, MD/PhD, Laetitia.DAHAN@ap-hm.fr
Institut Paoli Calmettes
Marseille
Christelle DE LA FOUCHARDIERE, MD, delafouchardierec@ipc.unicancer.fr
CHRU de Nancy
Nancy
Marie MULLER, MD, M.MULLER7@chru-nancy.fr
Hôpital Saint Antoine - APHP
Paris
Romain COHEN, MD, romain.cohen@aphp.fr
Hôpital Saint Louis - APHP
Paris
Thomas APARICIO, MD/PhD, thomas.aparicio@aphp.fr
Hôpital Privé des côtes d'Armor
Plérin
Jérôme MARTIN-BABAU, MD
CHU de Poitiers
Poitiers
David TOUGERON, MD, David.TOUGERON@chu-poitiers.fr
CHU de Reims
Reims
Olivier BOUCHE, MD/PhD, obouche@chu-reims.fr
Institut Jean Godinot
Reims
Damien BOTSEN, MD, Damien.BOTSEN@reims.unicancer.fr
CHU de Rouen
Rouen
Frédéric DI FIORE, MD, Frederic.Di-Fiore@chu-rouen.fr
Institut de Cancérologie de l'Ouest - Site René Gauducheau
Saint-Herblain
Héléne SENELLART, MD
Centre Hospitalier de Valenciennes
Valenciennes
Sébastien BORGES, MD
Gustave Roussy
Villejuif
Valérie BOIGE, MD, Valerie.Boige@gustaveroussy.fr
About this study
Official title: Randomized Phase 2 Study of Second-line Chemotherapy Comparing FOLFIRI + Ivonescimab Versus FOLFIRI + Bevacizumab in Microsatellite Stable (MSS)/ Proficient MisMatch Repair (pMMR) BRAF Wild Type (BRAFwt) Advanced Colorectal Cancer (mCRC) Without Liver Metastases
The goal of this clinical trial is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of PFS. The main questions it aims to answer are:
Does FOLFIRI + ivonescimab improve progression-free survival compared to FOLFIRI + bevacizumab?
Participants will:
Take FOLFIRI + ivonescimab or FOLFIRI + bevacizumab every 2 weeks for a maximum of 24 months Visit the clinic once every 2 weeks for checkups and tests, and have imaging done every 8 weeks Complete some quality of life questionnaires every 8 weeks
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Ivonescimab, Bevacizumab, FOLFIRI Protocol
- Keywords
- Metastatic colorectal cancer, ivonescimab, BRAF wild-type
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvonescimabDrug
Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)
BevacizumabDrug
Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)
FOLFIRI ProtocolDrug
FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks
| Study group | Role | What they receive |
|---|---|---|
| Ivonescimab + FOLFIRI | Experimental | Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks Receives: Drug: Ivonescimab; Drug: FOLFIRI Protocol |
| Bevacizumab + FOLFIRI | Active comparator | Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks Receives: Drug: Bevacizumab; Drug: FOLFIRI Protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression Free Survival (PFS)
The primary objective is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of Progression-Free Survival (PFS).
Measured: Time from the date of randomization until the date of first documented disease progression as assessed by the investigator according to RECIST1.1, or death from any cause, whichever came first, assessed up to 72 months.
Secondary outcomes (7)
PFS as per iRECIST
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of PFS as per iRECIST
Measured: The time from the date of randomization to the date of first documentation of disease progression as assessed by the investigator according to iRECIST, or death from any cause, whichever came first, assessed up to 72 months.
Overall Response Rate (ORR) as per RECIST v1.1
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of Overall Response Rate (ORR) as per RECIST v1.1. The proportion of patients achieving complete response (CR) or partial response (PR) as assessed by the investigator according to RECIST v1.1.
Measured: Imagery will be done within 28 days before first study treatment, and every 8 weeks until the date of the first documented disease progression.
Duration of Response (DOR) as per RECIST v1.1
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of Duration of Response (DOR) as per RECIST v1.1.
Measured: The time from first documented PR or CR (compared to baseline measurement done within 28 days before first study treatment) until the date of PD (Imagery done every 8 weeks), or death from any cause.
Overall Survival (OS)
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of Overall Survival (OS). The time from randomization to death from any cause. Patients who are alive at the data-cutoff date will be censored on the last known alive date.
Measured: From date of randomization until the date of death from any cause, whichever came first, assessed up to 72 months.
Safety and tolerability of treatment (NCI-CTCAE version 5.0)
Toxicity / Adverse events (AEs), occurrence of treatment-related AEs, treatment-related AEs (TRAEs) leading to dose reduction or discontinuation during treatment, serious adverse events (SAEs) and suspected unexpected serious adverse reactions (SUSARs), iand tolerability of treatment (NCI-CTCAE version 5.0)
Measured: At baseline within 14 days prior first study treatment, at day 1 of each visit during treatment (every 2 weeks), at the end of treatment (30 days after last study treatment), and at the two first follow-up (every 8 weeks after last administration).
The effect of treatments on Quality of Life (QoL) - QLQ-C30
QoL is assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaires QLQ-C30 and EORTC QLQ-CR29
Measured: At baseline within 14 days prior first study treatment, every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 72 months
The effect of treatments on Quality of Life (QoL) - QLQ-CR29
QoL is assessed using the European Organisation for Research and Treatment of Cancer
Measured: At baseline within 14 days prior first study treatment, every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 72 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2026
- Study start31 Aug 2026 (estimated)
- Primary completionAug 2029 (estimated)
- Study completionAug 2033 (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.
- More trials run by UNICANCERThe sponsor's other registered studies.
- 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
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- UNICANCER
- Sponsor type
- University, hospital or other
- Collaborators
- Summit Therapeutics
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07359456
- Sponsor's protocol ID
- UC-GIG-2518
- Other IDs
- 2025-524215-36-00, 2025
- Acronym
- COLIBRI-GI
- Status last verified
- Apr 2026
- First submitted
- 9 Dec 2025
- Last updated
- 19 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 2 Study of Second-line Chemotherapy Comparing FOLFIRI + Ivonescimab Versus FOLFIRI + Bevacizumab in Microsatellite Stable (MSS)/ Proficient MisMatch Repair (pMMR) BRAF Wild Type (BRAFwt) Advanced Colorectal Cancer (mCRC) Without Liver Metastases
- ClinicalTrials.gov ID
- NCT07359456
- Acronym / sponsor ID
- COLIBRI-GI / UC-GIG-2518
- Conditions
- Metastatic Colorectal Cancer
- Keywords
- Metastatic colorectal cancer, ivonescimab, BRAF wild-type
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- UNICANCERUniversity, hospital or other
- Collaborators
- Summit Therapeutics
- Study start
- 31 Aug 2026 (estimated)
- Primary completion
- Aug 2029 (estimated)
- Study completion
- Aug 2033 (estimated)
- First posted
- 22 Jan 2026 (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.
The goal of this clinical trial is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of PFS. The main questions it aims to answer are:
Does FOLFIRI + ivonescimab improve progression-free survival compared to FOLFIRI + bevacizumab?
Participants will:
Take FOLFIRI + ivonescimab or FOLFIRI + bevacizumab every 2 weeks for a maximum of 24 months Visit the clinic once every 2 weeks for checkups and tests, and have imaging done every 8 weeks Complete some quality of life questionnaires every 8 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivonescimab + FOLFIRI | Experimental | Drug: Ivonescimab, Drug: FOLFIRI ProtocolIvonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks |
| Bevacizumab + FOLFIRI | Active comparator | Drug: Bevacizumab, Drug: FOLFIRI ProtocolBevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) combined with FOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Signed a written informed consent form prior to any trial specific procedures. Note: If the patient is physically unable to provide their written consent, a trusted person of their choice, independent of the Investigator or the Sponsor, can confirm the patients consent in writing.
- Histologically confirmed diagnosis of non resectable pMMR (by IHC) and MSS (by molecular biology) and BRAFwt metastatic colorectal cancer with no liver metastasis.
- Must have previously received 1st-line treatment with FOLFOX +/- anti-VEGF (Vascular endothelial growth factor) or EGFR (Epithelial Growth Factor Receptor) therapy (including recurrence within 6 months after adjuvant FOLFOX for localized CRC and adjuvant/perioperative FOLFOX for mCRC, as well as progressive disease under maintenance treatment for mCRC) OR 1st-line treatment with FOLFIRINOX (Oxaliplatin, Irinotecan, 5FU, Folinic acid) (under the following condition: no progression under triplet-chemotherapy, progression under LV5FU2 (Folinic acid + 5FU) maintenance, irinotecan stopped for at least 3 months for a reason other than progression)
- Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Key exclusion criteria (34 listed)
- Presence of liver metastases by CT-scan or MRI. Note: Patients with prior definitively treated liver metastases (surgical resection, microwave or radiofrequency ablation, or stereotactic body radiation therapy) are eligible if no evidence of metastatic disease in the liver on subsequent imaging).
- History of Gilbert's syndrome
- Other current or previous malignancy within the past 3 years (with the exception of squamous cell carcinoma of the skin or in situ tumour treated by surgery).
- Patients with high microsatellite instability (MSI-H), mismatched repair disease (dMMR) and/or BRAF V600E mutated tumor.
- Toxicities from previous treatment not resolved to grade ≤ 1 (according to the version 5.0 of the National Cancer Institute - Common terminology criteria for adverse events [NCI-CTCAE v5.0]) before treatment start with the exception of alopecia.
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 |
|---|---|---|
| IvonescimabIvonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) | Drug | Ivonescimab + FOLFIRI |
| BevacizumabBevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W) | Drug | Bevacizumab + FOLFIRI |
| FOLFIRI ProtocolFOLFIRI chemotherapy (irinotecan 180 mg/m2 IV, folinic acid 400 mg/m2 IV (or L-folinic acid 200 mg/m²), and fluorouracil (5-FU) 400 mg/m² IV bolus; followed by 5 FU 2400 mg/m2 as a 46 hour continuous IV infusion), every two weeks | Drug | Bevacizumab + FOLFIRI, Ivonescimab + FOLFIRI |
Primary outcome
Progression Free Survival (PFS)
Time frame: Time from the date of randomization until the date of first documented disease progression as assessed by the investigator according to RECIST1.1, or death from any cause, whichever came first, assessed up to 72 months.
The primary objective is to evaluate the superiority of ivonescimab combined with FOLFIRI over FOLFIRI + bevacizumab as second-line treatment of non resectable pMMR/MSS BRAFwt mCRC patients without liver metastases in terms of Progression-Free Survival (PFS).
7 secondary outcomes
PFS as per iRECIST
Time frame: The time from the date of randomization to the date of first documentation of disease progression as assessed by the investigator according to iRECIST, or death from any cause, whichever came first, assessed up to 72 months.
Overall Response Rate (ORR) as per RECIST v1.1
Time frame: Imagery will be done within 28 days before first study treatment, and every 8 weeks until the date of the first documented disease progression.
Duration of Response (DOR) as per RECIST v1.1
Time frame: The time from first documented PR or CR (compared to baseline measurement done within 28 days before first study treatment) until the date of PD (Imagery done every 8 weeks), or death from any cause.
Overall Survival (OS)
Time frame: From date of randomization until the date of death from any cause, whichever came first, assessed up to 72 months.
Safety and tolerability of treatment (NCI-CTCAE version 5.0)
Time frame: At baseline within 14 days prior first study treatment, at day 1 of each visit during treatment (every 2 weeks), at the end of treatment (30 days after last study treatment), and at the two first follow-up (every 8 weeks after last administration).
The effect of treatments on Quality of Life (QoL) - QLQ-C30
Time frame: At baseline within 14 days prior first study treatment, every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 72 months
The effect of treatments on Quality of Life (QoL) - QLQ-CR29
Time frame: At baseline within 14 days prior first study treatment, every 8 weeks from date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 72 months
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 19 May 2026.
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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.
22 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 Ivonescimab, Bevacizumab and FOLFIRI Protocol in people with Metastatic Colorectal Cancer, run by UNICANCER at 22 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 23 inclusion and 34 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: opening soon, as of the sponsor's last update on 19 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 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 Emilie Brument (0668320359, e-brument@unicancer.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression Free Survival (PFS) (time frame: Time from the date of randomization until the date of first documented disease progression as assessed by the investigator according to RECIST1.1, or death from any cause, whichever came first, assessed up to 72 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 19 May 2026; AzTrials last refreshed its copy on 7 Nov 2026.