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NCT Number: NCT07228832

Phase III Study of Ivonescimab or Bevacizumab Combined With FOLFOX in Patients With Metastatic Colorectal Cancer

A Randomized, Active-Controlled, Double-blind, Multicenter, Phase 3 Clinical Study of Ivonescimab in Combination with mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) versus Bevacizumab in Combination with FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer(HARMONi-GI3)

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Key information

Conditions

Metastatic Colorectal Cancer (CRC) Colonic Diseases Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Intestinal Diseases Intestinal Neoplasms Neoplasms Neoplasms by Site Rectal Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Clinical Study Site, Brussels, Belgium

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About this study

This trial will be performed as a phase 3, randomized, active-controlled, double-blind, multiregional study comparing Ivonescimab in combination with mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) versus Bevacizumab in combination with mFOLFOX6 in patients with metastatic colorectal cancer who have not previously received systemic therapy for metastatic disease. Approximately 600 patients will be randomly assigned to the 2 treatment groups in a 1:1 ratio. Each enrolled subject will receive an intravenous infusion of the Ivonescimab/Bevacizumab Plus mFOLFOX6 (Q2W, up to 8 cycles) in treatment periods per the randomization schedule. Afterward, Ivonescimab/ Bevacizumab Plus 5-Fluorouracil and Leucovorin will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) for up to 2 years.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

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

Treatment and study plan

Drug: Ivonescimab Injection

Drug

Subjects will receive Ivonescimab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-Fluorouracil will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) for up to 2 years.

Other names: Oxaliplatin, Leucovorin, 5-Fluorouracil

Drug: Bevacizumab Injection

Drug

Subjects will receive bevacizumab Plus mFOLFOX6 (Oxaliplatin, Leucovorin and 5-Fluorouracil) via intravenous infusion (IV) Q2W, up to 8 cycles in treatment periods per the randomization schedule. Afterward, bevacizumab Plus 5-FU and Leucovorin will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years.

Other names: Oxaliplatin, Leucovorin, 5-Fluorouracil

Primary outcomes

  1. PFS by IRRC based on RECIST v1.1

    Time frame: Up to approximately 2.5 years

    Progression-free survival (PFS) assessed by IRRC per RECIST v1.1

Secondary outcomes

  1. Overall Survival (OS) in the population

    Time frame: Up to approximately 4 years

    Overall Survival (OS) in the mCRC population

  2. ORR

    Time frame: Up to approximately 2.5 years

    Efficacy measures such as overall response rate (ORR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1

  3. Adverse Events (AE)

    Time frame: Up to approximately 4 years

    incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results [From the time subject signs the ICF to 30 days (AE) and 90 days (SAE related to ivonescimab/bevacizumab) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first]

  4. DoR

    Time frame: up to approximately 2.5 years

    Efficacy measures such as duration of response (DoR), which is the proportion of subjects with CR or PR by IRRC based on RECIST v1.1

Study contacts

Contact information is provided by the study sponsor or research team.

Ning Chang, MD

CONTACT

[email protected]

1-833-256-0522

Sponsors and collaborators

Lead sponsor

Summit Therapeutics

Industry

Registry information

Official study 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

Acronym: HARMONi-GI3

Important dates

Study start
2025
Primary completion
2028
Study completion
2029
First posted
Nov 14, 2025
Registry last updated
Jul 6, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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