Testing Ivonescimab in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancers Without Liver Metastases (COLIBRI-GI)

May 18, 2026 updated by: UNICANCER

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

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

130

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • France
      • Auxerre, France
        • CH d'Auxerre
        • Contact:
          • Anne-Laure VILLING, MD
      • Beuvry, France
        • Centre Hospitalier de Beuvry
        • Contact:
          • Hélène VAN DAMME, MD
      • Caen, France
      • Calais, France
        • CH de Calais
        • Contact:
          • Nathalie IBRAHIM, MD
      • Compiègne, France
        • Polyclinique Saint Côme
        • Contact:
          • Kaïs ALDABBAGH, MD
      • Coudekerque-Branche, France
        • Institut Andrée Dutreix
        • Contact:
          • Jean-Baptiste AISENFARB, MD
      • Lille, France
      • Lyon, France
        • Centre Leon Berard
        • Contact:
          • Clélia COUTZAC, MD
      • Marseille, France
      • Marseille, France
      • Marseille, France
        • Hôpital Européen de Marseille
        • Contact:
          • Nicolas BARRIERE, MD
      • Nancy, France
      • Paris, France
      • Paris, France
      • Plérin, France
        • Hôpital privé des Côtes d'Armor
        • Contact:
          • Jérôme MARTIN-BABAU, MD
      • Poitiers, France
      • Reims, France
      • Reims, France
      • Rouen, France
      • Saint-Herblain, France
        • Institut de Cancérologie de l'Ouest - Site René Gauducheau
        • Contact:
          • Héléne SENELLART, MD
      • Valenciennes, France
        • Centre hospitalier de valenciennes
        • Contact:
          • Sébastien BORGES, MD
      • Villejuif, France

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. 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.
  2. Histologically confirmed diagnosis of non resectable pMMR (by IHC) and MSS (by molecular biology) and BRAFwt metastatic colorectal cancer with no liver metastasis.
  3. 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)
  4. Presence of at least one measurable lesion as assessed by the investigator according to RECIST v1.1.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. Age ≥18 years.

  7. 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)
  8. Life expectancy ≥ 3 months
  9. 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.
  10. 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.
  11. 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
  12. Affiliation to the Social Security System (or equivalent)

Exclusion Criteria:

  1. 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).
  2. History of Gilbert's syndrome
  3. 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).
  4. Patients with high microsatellite instability (MSI-H), mismatched repair disease (dMMR) and/or BRAF V600E mutated tumor.
  5. 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.
  6. 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.

  7. 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.
  8. Current hypertension with systolic blood pressure ≥ 150 mmHg or diastolic blood pressure ≥ 100 mmHg after oral antihypertensive therapy

  9. 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
  10. Current presence of significant radiographic or clinical manifestations of gastrointestinal (GI) obstruction.
  11. Ascites requiring paracentesis within last 30 days
  12. 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.
  13. Presence of brainstem, meningeal metastases, spinal cord metastases, or compression.
  14. Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
  15. 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.

  16. 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.

  17. Known history of, or any evidence of, interstitial lung disease.
  18. 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).
  19. 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)
  20. Proven complete deficiency of dihydropyrimidine dehydrogenase (DPD).
  21. Known history of hypersensitivity to ivonescimab and to one of the study drugs or one of its excipients
  22. 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.
  23. Pregnant or breast-feeding females.
  24. Participation in another therapeutic trial within the 30 days prior to entering the study. Participation in an observational trial would be acceptable.
  25. Patients unwilling or unable to comply with the medical follow-up required by the trial because of geographic, familial, social, or psychological reasons.
  26. Individuals deprived of liberty or placed under protective custody or guardianship.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Ivonescimab + FOLFIRI
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
Drug: Ivonescimab
Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)
Drug: FOLFIRI Protocol
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
Active Comparator: Bevacizumab + FOLFIRI
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
Drug: FOLFIRI Protocol
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
Drug: Bevacizumab
Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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).
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of PFS as per iRECIST
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.
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.
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.
To evaluate the efficacy of ivonescimab in combination with FOLFIRI in terms of Duration of Response (DOR) as per RECIST v1.1.
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.
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.
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).
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)
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
QoL is assessed using the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaires QLQ-C30 and EORTC QLQ-CR29
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
QoL is assessed using the European Organisation for Research and Treatment of Cancer
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

UNICANCER

Collaborators

Summit Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 31, 2026

Primary Completion (Estimated)

August 1, 2029

Study Completion (Estimated)

August 1, 2033

Study Registration Dates

First Submitted

December 9, 2025

First Submitted That Met QC Criteria

January 13, 2026

First Posted (Actual)

January 22, 2026

Study Record Updates

Last Update Posted (Actual)

May 19, 2026

Last Update Submitted That Met QC Criteria

May 18, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • UC-GIG-2518
  • 2025-524215-36-00 (Ctis)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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