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Ivonescimab versus bevacizumab with FOLFOX for first-line metastatic colorectal cancer

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

PHASE3 · Summit Therapeutics · NCT07228832

This study tests whether ivonescimab combined with FOLFOX works as well as bevacizumab with FOLFOX for people starting first-line treatment for metastatic colorectal cancer.

Quick facts

PhasePHASE3
Study typeInterventional
Enrollment600 (estimated)
Ages18 Years and up
SexAll
SponsorSummit Therapeutics (industry)
Drugs / interventionsimmunotherapy, Ivonescimab, Bevacizumab
Locations76 sites (Goodyear, Arizona and 75 other locations)
Trial IDNCT07228832 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, active-controlled, multicenter Phase 3 trial that will enroll about 600 patients with metastatic colorectal cancer who have not received prior systemic therapy for metastatic disease. Participants will be assigned 1:1 to receive either ivonescimab plus mFOLFOX6 or bevacizumab plus mFOLFOX6, given by intravenous infusion every two weeks for up to eight cycles. After combination therapy, patients may continue maintenance treatment with the assigned antibody plus 5-fluorouracil and leucovorin every two weeks for up to two years. The study compares clinical outcomes and safety between the two antibody-containing regimens.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed metastatic colorectal cancer, ECOG 0–1, at least one measurable noncerebral lesion, no prior systemic therapy for metastatic disease, and without MSI-H/dMMR or BRAF V600E mutations.

Not a fit: Patients with MSI-H/dMMR or BRAF V600E mutations, prior immunotherapy or anti-angiogenic therapy for colorectal cancer, active inflammatory bowel disease, recent clinically significant ascites or GI obstruction, or resectable disease are excluded and unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, ivonescimab could provide an alternative targeted antibody option that improves outcomes or tolerability compared with bevacizumab for first-line metastatic colorectal cancer.

How similar studies have performed: Bevacizumab plus FOLFOX is an established first-line regimen and other anti-angiogenic antibodies have shown benefit, but ivonescimab is a novel agent being tested head-to-head against bevacizumab.

Eligibility criteria

Show full inclusion / exclusion criteria 
Inclusion Criteria:

1. ECOG performance status score of 0 or 1
2. Expected life expectancy ≥ 6 months
3. Patients with histologically or cytologically confirmed metastatic CRC
4. No prior systemic therapy for metastatic CRC
5. At least 1 measurable noncerebral lesion

Exclusion Criteria:

1. Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) disease
2. Known BRAF V600E mutant status
3. Current presence of significant radiographic or clinical manifestations of gastrointestinal (GI) obstruction
4. Ascites requiring paracentesis within last 30 days
5. Patients who have received prior immunotherapy or anti-angiogenic therapy for colorectal cancer
6. Active or prior history of inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis, or chronic diarrhea)
7. Resectable disease

Where this trial is running

Goodyear, Arizona and 75 other locations

+26 more sites — see ClinicalTrials.gov for the full list.

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Metastatic Colorectal Cancer, mCRC, Ivonescimab

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.