Testing Ivonescimab in Combination With Chemotherapy in Patients With Metastatic Colorectal Cancers Without Liver Metastases

NCT07359456 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: UC-GIG-25182025-524215-36-00
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 22

Brief 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. 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

Keywords

Metastatic colorectal cancer; ivonescimab; BRAF wild-type

Outcome Measures

Primary Outcomes (1)

• 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).

  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

  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

  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

  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)

  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)

  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).

Study Arms (2)

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

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

Drug: Bevacizumab; Drug: FOLFIRI Protocol

Interventions

Ivonescimab DRUG

Ivonescimab 20 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)

Ivonescimab + FOLFIRI

Bevacizumab DRUG

Bevacizumab 5 mg/kg by intravenous infusion (IV) once every 2 weeks (Q2W)

Bevacizumab + FOLFIRI

FOLFIRI Protocol DRUG

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; Ivonescimab + FOLFIRI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• UNICANCER: lead
• Summit Therapeutics: collaborator

Study Sites (22)

CH d'Auxerre

Auxerre, France

Location

Centre Hospitalier de Beuvry

Beuvry, France

Location

Centre François Baclesse

Caen, France

Location

CH de Calais

Calais, France

Location

Polyclinique Saint Côme

Compiègne, France

Location

Institut Andrée Dutreix

Coudekerque-Branche, France

Location

Centre Oscar Lambret

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Hôpital Européen de Marseille

Marseille, France

Location

Hôpital la Timone

Marseille, France

Location

Institut Paoli Calmettes

Marseille, France

Location

CHRU de Nancy

Nancy, France

Location

Hôpital Saint Antoine - APHP

Paris, France

Location

Hôpital Saint Louis - APHP

Paris, France

Location

Hôpital Privé des côtes d'Armor

Plérin, France

Location

CHU de Poitiers

Poitiers, France

Location

CHU de Reims

Reims, France

Location

Institut Jean Godinot

Reims, France

Location

CHU de Rouen

Rouen, France

Location

Institut de Cancérologie de l'Ouest - Site René Gauducheau

Saint-Herblain, France

Location

Centre Hospitalier de Valenciennes

Valenciennes, France

Location

Gustave Roussy

Villejuif, France

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; IFL protocol

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Emilie Brument

CONTACT

0668320359; e-brument@unicancer.fr

Valérie BOIGE, MD

CONTACT

0630582651; Valerie.Boige@gustaveroussy.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: January 22, 2026
• Study Start: March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2032
• Last Updated: January 22, 2026

Record last verified: 2025-10

Locations

FR (22)