RecruitingPhase 3NCT07228832

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 FOLFOX Versus Bevacizumab in Combination With FOLFOX for the First-line Treatment of Metastatic Colorectal Cancer


Sponsor

Summit Therapeutics

Enrollment

600 participants

Start Date

Nov 18, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

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)


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • 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 Criteria7

  • 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

Interventions

DRUGDrug: Ivonescimab Injection

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.

DRUGDrug: Bevacizumab Injection

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.


Locations(40)

Clinical Study Site

Goodyear, Arizona, United States

Clinical Study Site

Beverly Hills, California, United States

Clinical Study Site

Cerritos, California, United States

Clinical Study Site

Corona, California, United States

Clinical Study Site

Duarte, California, United States

Clinical Study Site

Huntington Beach, California, United States

Clinical Study Site

Irvine, California, United States

Clinical Study Site

Irvine, California, United States

Clinical Study Site

Los Angeles, California, United States

Clinical Study Site

Murrieta, California, United States

Clinical Study Site

Orange, California, United States

Clinical Study Site

Pasadena, California, United States

Clinical Study Site

Torrance, California, United States

Clinical Study Site

Upland, California, United States

Clinical Study Site

West Hollywood, California, United States

Clinical Study Site

New Haven, Connecticut, United States

Clinical Study Site

Norwich, Connecticut, United States

Clinical Study Site

Hialeah, Florida, United States

Clinical Study Site

Port Saint Lucie, Florida, United States

Clinical Study Site

Newnan, Georgia, United States

Clinical Study Site

Elmhurst, Illinois, United States

Clinical Study Site

O'Fallon, Illinois, United States

Clinical Study Site

Fort Wayne, Indiana, United States

Clinical Study Site

Edgewood, Kentucky, United States

Clinical Study Site

Saint Louis Park, Minnesota, United States

Clinical Study Site

Billings, Montana, United States

Clinical Study Site

Lincoln, Nebraska, United States

Clinical Study Site

Cincinnati, Ohio, United States

Clinical Study Site

Hermitage, Tennessee, United States

Clinical Study Site

Fort Worth, Texas, United States

Clinical Study Site

Salt Lake City, Utah, United States

Clinical Study Site

Spokane, Washington, United States

Clinical Study Site

Tacoma, Washington, United States

Clinical Study Site

Montreal, Quebec, Canada

Clinical Study Site

Chiba, Japan

Clinical Study Site

Fukuoka, Japan

Clinical Study Site

Hokkaido, Japan

Clinical Study Site

Osaka, Japan

Clinical Study Site

Tokyo, Japan

Clinical Study Site

Rio Piedras, Puerto Rico

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NCT07228832


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