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

Last updated: May 1, 2026
Sponsor: Summit Therapeutics
Overall Status: Active - Recruiting

Phase

3

Condition

N/A

Treatment

Drug: Ivonescimab Injection

Drug: Bevacizumab Injection

Clinical Study ID

NCT07228832
SMT112-3005
  • Ages > 18
  • All Genders

Study 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 Criteria

Inclusion

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

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 ofgastrointestinal (GI) obstruction

  4. Ascites requiring paracentesis within last 30 days

  5. Patients who have received prior immunotherapy or anti-angiogenic therapy forcolorectal cancer

  6. Active or prior history of inflammatory bowel disease (eg, Crohn's disease,ulcerative colitis, or chronic diarrhea)

  7. Resectable disease

Study Design

Total Participants: 600
Treatment Group(s): 2
Primary Treatment: Drug: Ivonescimab Injection
Phase: 3
Study Start date:
November 18, 2025
Estimated Completion Date:
November 30, 2029

Study Description

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.

Connect with a study center

  • Clinical Study Site

    Montreal, Quebec H4A 3J1
    Canada

    Active - Recruiting

  • Clinical Study Site

    Montreal 6077243, Quebec 6115047 H4A 3J1
    Canada

    Site Not Available

  • Clinical Study Site

    Aichi, 464-8681
    Japan

    Active - Recruiting

  • Clinical Study Site

    Chiba, 260-8717
    Japan

    Active - Recruiting

  • Clinical Study Site

    Chiba 2113015, 260-8717
    Japan

    Site Not Available

  • Clinical Study Site

    Fukuoka, 812-8582
    Japan

    Active - Recruiting

  • Clinical Study Site

    Fukuoka 1863967, 812-8582
    Japan

    Site Not Available

  • Clinical Study Site

    Gifu, 501-1194
    Japan

    Active - Recruiting

  • Clinical Study Site

    Hiroshima, 734-8551
    Japan

    Active - Recruiting

  • Clinical Study Site

    Hokkaido, 060-8648
    Japan

    Active - Recruiting

  • Clinical Study Site

    Kawasaki, 216-8511
    Japan

    Active - Recruiting

  • Clinical Study Site

    Osaka, 541-8567
    Japan

    Active - Recruiting

  • Clinical Study Site

    Osaka 1853909, 541-8567
    Japan

    Site Not Available

  • Clinical Study Site

    Sendai, 980-0872
    Japan

    Active - Recruiting

  • Clinical Study Site

    Shizuoka, 411-8777
    Japan

    Active - Recruiting

  • Clinical Study Site

    Tokyo, 135-8550
    Japan

    Active - Recruiting

  • Clinical Study Site

    Tokyo 1850147, 104-0045
    Japan

    Site Not Available

  • Clinical Study Site

    Toyama, 930-0194
    Japan

    Active - Recruiting

  • Clinical Study Site

    Rio Piedras, 00935
    Puerto Rico

    Active - Recruiting

  • Clinical Study Site

    Rio Piedras 4829037, 00935
    Puerto Rico

    Site Not Available

  • Clinical Study Site

    Canterbury, England CT13NS
    United Kingdom

    Active - Recruiting

  • Clinical Study Site

    London, England EC1M 6BQ
    United Kingdom

    Active - Recruiting

  • Clinical Study Site

    Aberdeen, Scotland AB25 2ZN
    United Kingdom

    Active - Recruiting

  • Clinical Study Site

    Goodyear, Arizona 85338
    United States

    Active - Recruiting

  • Clinical Study Site

    Goodyear 5296266, Arizona 5551752 85338
    United States

    Site Not Available

  • Clinical Study Site

    Beverly Hills, California 90211
    United States

    Active - Recruiting

  • Clinical Study Site

    Cerritos, California 90703
    United States

    Active - Recruiting

  • Clinical Study Site

    Corona, California 92882
    United States

    Active - Recruiting

  • Clinical Study Site

    Duarte, California 91010
    United States

    Active - Recruiting

  • Clinical Study Site

    Fountain Valley, California 92708
    United States

    Active - Recruiting

  • Clinical Study Site

    Huntington Beach, California 92648
    United States

    Active - Recruiting

  • Clinical Study Site

    Irvine, California 92612
    United States

    Active - Recruiting

  • Clinical Study Site

    Los Angeles, California 90067
    United States

    Active - Recruiting

  • Clinical Study Site

    Murrieta, California 92562
    United States

    Active - Recruiting

  • Clinical Study Site

    Orange, California 92868
    United States

    Active - Recruiting

  • Clinical Study Site

    Pasadena, California 91030
    United States

    Active - Recruiting

  • Clinical Study Site

    Torrance, California 90503
    United States

    Active - Recruiting

  • Clinical Study Site

    Upland, California 91786
    United States

    Active - Recruiting

  • Clinical Study Site

    West Hollywood, California 90048
    United States

    Active - Recruiting

  • Clinical Study Site

    Beverly Hills 5328041, California 5332921 90212
    United States

    Site Not Available

  • Clinical Study Site

    Cerritos 5335663, California 5332921 90703
    United States

    Site Not Available

  • Clinical Study Site

    Corona 5339631, California 5332921 92882
    United States

    Site Not Available

  • Clinical Study Site

    Duarte 5344147, California 5332921 91010
    United States

    Site Not Available

  • Clinical Study Site

    Huntington Beach 5358705, California 5332921 92648
    United States

    Site Not Available

  • Clinical Study Site

    Irvine 5359777, California 5332921 92612
    United States

    Site Not Available

  • Clinical Study Site

    Los Angeles 5368361, California 5332921 90067
    United States

    Site Not Available

  • Clinical Study Site

    Murrieta 5375911, California 5332921 92562
    United States

    Site Not Available

  • Clinical Study Site

    Orange 5379513, California 5332921 92868
    United States

    Site Not Available

  • Clinical Study Site

    Pasadena 5381396, California 5332921 91030
    United States

    Site Not Available

  • Clinical Study Site

    Torrance 5403022, California 5332921 90503
    United States

    Site Not Available

  • Clinical Study Site

    Upland 5404915, California 5332921 91786
    United States

    Site Not Available

  • Clinical Study Site

    West Hollywood 5408076, California 5332921 90048
    United States

    Site Not Available

  • Clinical Study Site

    Hartford, Connecticut 06106
    United States

    Active - Recruiting

  • Clinical Study Site

    New Haven, Connecticut 06520-8028
    United States

    Active - Recruiting

  • Clinical Study Site

    Norwich, Connecticut 06360
    United States

    Active - Recruiting

  • Clinical Study Site

    New Haven 4839366, Connecticut 4831725 06520-8028
    United States

    Site Not Available

  • Clinical Study Site

    Norwich 4839843, Connecticut 4831725 06360
    United States

    Site Not Available

  • Clinical Study Site

    Hialeah, Florida 33013
    United States

    Active - Recruiting

  • Clinical Study Site

    Miami, Florida 33176
    United States

    Active - Recruiting

  • Clinical Study Site

    Orlando, Florida 32806
    United States

    Active - Recruiting

  • Clinical Study Site

    Plantation, Florida 33322
    United States

    Active - Recruiting

  • Clinical Study Site

    Port Saint Lucie, Florida 34952
    United States

    Active - Recruiting

  • Clinical Study Site

    Tamarac, Florida 33321
    United States

    Active - Recruiting

  • Clinical Study Site

    Hialeah 4158476, Florida 4155751 33013
    United States

    Site Not Available

  • Clinical Study Site

    Port Saint Lucie 4169171, Florida 4155751 34952
    United States

    Site Not Available

  • Clinical Study Site

    Newnan, Georgia 30265
    United States

    Active - Recruiting

  • Clinical Study Site

    Newnan 4212684, Georgia 4197000 30265
    United States

    Site Not Available

  • Clinical Study Site

    Chicago, Illinois 60611
    United States

    Active - Recruiting

  • Clinical Study Site

    Elmhurst, Illinois 60540
    United States

    Active - Recruiting

  • Clinical Study Site

    O'Fallon, Illinois 62269
    United States

    Active - Recruiting

  • Clinical Study Site

    Elmhurst 4891010, Illinois 4896861 60540
    United States

    Site Not Available

  • Clinical Study Site

    O'Fallon 4245926, Illinois 4896861 62269
    United States

    Site Not Available

  • Clinical Study Site

    Fort Wayne, Indiana 46804
    United States

    Active - Recruiting

  • Clinical Study Site

    Indianapolis, Indiana 46202
    United States

    Active - Recruiting

  • Clinical Study Site

    Fort Wayne 4920423, Indiana 4921868 46804
    United States

    Site Not Available

  • Clinical Study Site

    Edgewood, Kentucky 41017
    United States

    Active - Recruiting

  • Clinical Study Site

    Edgewood 4290873, Kentucky 6254925 41017
    United States

    Site Not Available

  • Clinical Study Site

    Saint Louis Park, Minnesota 55426
    United States

    Active - Recruiting

  • Clinical Study Site

    Saint Louis Park 5045021, Minnesota 5037779 55426
    United States

    Site Not Available

  • Clinical Study Site

    Billings, Montana 59102
    United States

    Active - Recruiting

  • Clinical Study Site

    Billings 5640350, Montana 5667009 59102
    United States

    Site Not Available

  • Clinical Study Site

    Lincoln, Nebraska 68506
    United States

    Active - Recruiting

  • Clinical Study Site

    Lincoln 5072006, Nebraska 5073708 68506
    United States

    Site Not Available

  • Clinical Study Site

    New Brunswick, New Jersey 08901
    United States

    Active - Recruiting

  • Clinical Study Site

    Mineola, New York 11501
    United States

    Active - Recruiting

  • Clinical Study Site

    New York, New York 10016
    United States

    Active - Recruiting

  • Clinical Study Site

    The Bronx, New York 10461
    United States

    Active - Recruiting

  • Clinical Study Site

    Akron, Ohio 44032
    United States

    Active - Recruiting

  • Clinical Study Site

    Canton, Ohio 44703
    United States

    Active - Recruiting

  • Clinical Study Site

    Cincinnati, Ohio 45220
    United States

    Active - Recruiting

  • Clinical Study Site

    Cleveland, Ohio 44195
    United States

    Active - Recruiting

  • Clinical Study Site

    Mayfield Heights, Ohio 44124
    United States

    Active - Recruiting

  • Clinical Study Site

    Cincinnati 4508722, Ohio 5165418 45220
    United States

    Site Not Available

  • Clinical Study Site

    Philadelphia, Pennsylvania 19140
    United States

    Active - Recruiting

  • Clinical Study Site

    Hermitage, Tennessee 37129
    United States

    Active - Recruiting

  • Clinical Study Site

    Hermitage 4628929, Tennessee 4662168 37129
    United States

    Site Not Available

  • Clinical Study Site

    Fort Worth, Texas 76104
    United States

    Active - Recruiting

  • Clinical Study Site

    Fort Worth 4691930, Texas 4736286 76104
    United States

    Site Not Available

  • Clinical Study Site

    Salt Lake City, Utah 84106
    United States

    Active - Recruiting

  • Clinical Study Site

    Salt Lake City 5780993, Utah 5549030 84106
    United States

    Site Not Available

  • Clinical Study Site

    Charlottesville, Virginia 22908
    United States

    Active - Recruiting

  • Clinical Study Site

    Spokane, Washington 99208
    United States

    Active - Recruiting

  • Clinical Study Site

    Tacoma, Washington 98405
    United States

    Active - Recruiting

  • Clinical Study Site

    Spokane 5811696, Washington 5815135 99208
    United States

    Site Not Available

  • Clinical Study Site

    Tacoma 5812944, Washington 5815135 98405
    United States

    Site Not Available

  • Clinical Study Site

    Charleston, West Virginia 25304
    United States

    Active - Recruiting

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