Taking people in ItalyPhase 3
Tests ivonescimab with chemotherapy against bevacizumab with chemotherapy in colorectal cancer
Tests ivonescimab plus chemotherapy against bevacizumab plus chemotherapy in adults with metastatic colorectal cancer.
Key facts
- Who runs it
- Summit Therapeutics Inc.
- Where
- Aviano, Bologna, Brescia, Cagliari, Candiolo, Catania, Florence, Genoa, Meldola, Milan, Naples, Orbassano, Padova, Pisa, Rome, Rozzano, San Giovanni Rotondo, and Verona, ItalySee the 20 sitesAlso in 8 other countries, 88 sites
- Trial code
- Registry title
- A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination with FOLFOX versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer (HARMONi-GI3)
- Status
- Recruiting
- Phase
- Phase 3
- People taking part
- 230 people, planned
- Started
- 3 Jun 2026
- Expected to end
- 28 Jul 2028
- Type of study
- Interventional
- Record updated
- 16 October 2026
Who can take part
AI summary
From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.
The trial is looking for adults with colorectal cancer that has spread and cannot be removed by surgery, who have not yet had drug treatment for the spread.
- Age
- 18 years or older
- Sex
- All sexes can join
- Disease stage
- Metastatic colorectal cancer confirmed by tissue or cell tests, not removable by surgery. At least one tumor that can be measured. ECOG performance status of 0 or 1.
- Earlier treatment
- No earlier systemic therapy for metastatic colorectal cancer. If treatment was given for early-stage disease, more than 12 months must have passed since it ended and before the cancer came back or spread. No earlier immunotherapy or anti-angiogenic therapy for colorectal cancer.
- Biomarker or test result
- BRAF, KRAS and NRAS (extended RAS) mutation status must be known from existing reports or tested on tumor tissue.
Main reasons for not taking part
- Known MSI-H/dMMR disease
- Known BRAF V600E mutation or known DPD deficiency
- Symptomatic brain or spinal cord metastases with bleeding, metastasis of 1.5 cm (0.6 in) or more, or leptomeningeal disease
- Disease that is only a few spots and can be fully removed by surgery
- Fluid in the belly needing drainage in the last 30 days
The registry criteria, word for word
Show all 11 criteriaShow less
Who can take part
- Histologically or cytologically confirmed mCRC, not amenable to curative resection
- An Eastern Cooperative Oncology Organization Group (ECOG) performance status score of 0 or 1
- No prior systemic therapy for mCRC. NOTE:- If patients have received systemic therapy or radiotherapy for early-stage disease, >12 months must have elapsed since completion of neoadjuvant therapy and/or adjuvant therapy (including adjuvant oxaliplatin or radiotherapy) and prior to diagnosis of recurrent or metastatic disease
- At least one measurable tumor lesion according to RECIST v1.1 that is amenable to repeated accurate measurements. NOTE:- Brain metastases cannot be selected as target lesions and lesions that have received radiotherapy in the past cannot be selected as target lesions unless they have progressed following radiation
- Known BRAF, KRAS and NRAS (extended RAS) mutation status from existing reports, or determined by testing tumor tissue utilizing a clinical assay
Who cannot take part
- Known BRAF V600E mutation status. known DPD deficiency (refer to local fluorouracil label or local clinical guidance for DPD status recommendation prior to starting treatment)
- Patients who have received prior immunotherapy or anti-angiogenic therapy for colorectal cancer, including immune checkpoint inhibitors, immune checkpoint agonists, immune cell therapy and any other therapy based on the mechanism of action of tumor immunity or angiogenesis
- Symptomatic central nervous system (CNS) metastases with hemorrhagic features, CNS metastasis ≥ 1.5 cm, CNS radiation within 7 days prior to randomization, potential need for CNS radiation within the first cycle, or leptomeningeal disease. NOTE:- Patients who have stopped corticosteroids or on stable corticosteroid therapy (prednisone ≤ 10 mg daily or equivalent) are allowed
- Resectable oligometastastic-only disease with multidisciplinary plan for complete resection of all disease
- Patients with known MSI-H/dMMR disease as determined by a health authority approved assay (eg, FDA for United States, CE-IVD marked for Europe, PMDA for Japan, and NMPA for China) conducted at a local clinical laboratory or at the central laboratory
- Ascites requiring paracentesis within last 30 days
Check if you might fit
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- How many different drug treatment plans (such as chemotherapy) have you had for cancer that has spread?
- Has a test of your tumour shown a change (mutation) in the KRAS, NRAS or BRAF genes?
- Has a test shown that your tumour is 'MSI-high' or 'dMMR'?
- Which best describes how well you can look after yourself and be active?
Where in Italy
Also in 8 other countries, 88 sites
- Centro di Riferimento Oncologico di AvianoAviano, ItalyTaking people
- Azienda Ospedaliero-Universitaria Di Bologna IRCCS Istituto Di Ricerca E Di Cura A Carattere ScientificoBologna, ItalyTaking people
- Fondazione PoliambulanzaBrescia, ItalyTaking people
- Azienda Ospedaliero - Universitaria di CagliariCagliari, ItalyTaking people
- Istituto di Candiolo Fondazione del Piemonte per l'oncologia IRCCSCandiolo, ItalyTaking people
- ARNAS Garibaldi Di CataniaCatania, ItalyTaking people
- Azienda Ospedaliero-Universitaria CareggiFlorence, ItalyTaking people
- IRCCS Azienda Ospedaliera MetropolitanaGenoa, ItalyTaking people
- IRCCS Ospedale Policlinico San MartinoGenoa, ItalyTaking people
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.lMeldola, ItalyTaking people
- ASST Grande Ospedale Metropolitano NiguardaMilan, ItalyTaking people
- Istituto Europeo di Oncologia s.r.lMilan, ItalyTaking people
- Azienda Ospedaliera Universitaria - Universita degli Studi della Campania Luigi VanvitelliNaples, ItalyTaking people
- Azienda Ospedaliero-Universitaria San Luigi GonzagaOrbassano, ItalyTaking people
- Istituto Oncologico VenetoPadova, ItalyTaking people
- Azienda Ospedaliero Universitaria PisanaPisa, ItalyTaking people
- I.F.O. Istituti Fisioterapici OspitalieriRome, ItalyTaking people
- Humanitas Mirasole S.p.A.Rozzano, ItalyTaking people
- Casa Sollievo della SofferenzaSan Giovanni Rotondo, ItalyTaking people
- Centro Ricerche Cliniche di Verona s.r.l.Verona, ItalyTaking people
About the trial
What the trial wants to find out
To compare the progression-free survival (PFS) as assessed by blinded Independent Radiological Review Committee (IRRC) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, of ivonescimab in combination with modified 5 FU, oxaliplatin, and leucovorin (mFOLFOX6) to bevacizumab in combination with mFOLFOX6.
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Contact the study team: see the registry record
Print a page for my doctorData and sources
- Registry record
- Listed on the EU's official list of trials (CTIS).
- Official title
- A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination with FOLFOX versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer (HARMONi-GI3)
- Plain-language title
- Tests ivonescimab with chemotherapy against bevacizumab with chemotherapy in colorectal cancerGenerated from the registry record. The registry title is the official one.
- AI summary
- From the trial's eligibility criteria. Read by machine on 9 November 2026.
- Fit questions
- Built from 2025-521587-35-00, who can take part
- Record updated
- 16 October 2026