Metastatic Colorectal Cancer (CRC)Phase 3HARMONi-GI3NCT07228832

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

A Phase 3 study testing Drug: Ivonescimab Injection and Drug: Bevacizumab Injection in people with Metastatic Colorectal Cancer (CRC), run by Summit Therapeutics at 243 sites in 15 countries.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts

Official record

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Trial 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) Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Metastatic Colorectal Cancer (CRC)
What is being tested?: Drug: Ivonescimab Injection and Drug: Bevacizumab Injection
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 900 participants
Where: 243 sitesin 15 countries
Study dates: 18 Nov 2025to 30 Nov 2029
Phase: Phase 3
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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

Who cannot join

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

Trial locations and contacts

243 sites in 15 countries. Contact the study team or a site near you to ask about taking part.

Ning Chang, MD contact

1-833-256-0522

medicalaffairs@summitplc.com

Country

City, postcode or hospital

Sites recruiting now only

243 sites in 15 countries

United States112 sites, 112 recruiting

Clinical Study Site
Akron, Ohio, 44032
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Clinical Study Site
Atlanta, Georgia, 30303
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Clinical Study Site
Atlanta, Georgia, 30322
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Clinical Study Site
Aurora, Colorado, 80045
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Clinical Study Site
Baltimore, Maryland, 21201
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Clinical Study Site
Beverly Hills, California, 90211
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Clinical Study Site
Beverly Hills, California, 90212
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Clinical Study Site
Billings, Montana, 59102
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Clinical Study Site
Boston, Massachusetts, 02114
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Clinical Study Site
Burlington, Vermont, 05401
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Clinical Study Site
Camden, New Jersey, 08103
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Clinical Study Site
Canton, Ohio, 44703
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Clinical Study Site
Cerritos, California, 90703
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Clinical Study Site
Charleston, West Virginia, 25304
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Clinical Study Site
Charlottesville, Virginia, 22908
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Clinical Study Site
Chicago, Illinois, 60611
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Clinical Study Site
Chicago, Illinois, 60612
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Clinical Study Site
Cincinnati, Ohio, 45219
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Clinical Study Site
Cincinnati, Ohio, 45220
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Clinical Study Site
Cleveland, Ohio, 44111
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Clinical Study Site
Cleveland, Ohio, 44195
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Clinical Study Site
Corona, California, 92882
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Clinical Study Site
Dallas, Texas, 75235
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Clinical Study Site
Dallas, Texas, 75390
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Clinical Study Site
Danvers, Massachusetts, 01923
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Clinical Study Site
Denver, Colorado, 80206
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Clinical Study Site
Detroit, Michigan, 48201
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Clinical Study Site
Duarte, California, 91010
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Clinical Study Site
Edgewood, Kentucky, 41017
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Clinical Study Site
Elmhurst, Illinois, 60540
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Clinical Study Site
Fairfax, Virginia, 22031
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Clinical Study Site
Fort Wayne, Indiana, 46804
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Clinical Study Site
Fort Worth, Texas, 76104
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Clinical Study Site
Fountain Valley, California, 92708
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Clinical Study Site
Germantown, Tennessee, 38138
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Clinical Study Site
Goodyear, Arizona, 85338
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Clinical Study Site
Greenville, South Carolina, 29605
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Clinical Study Site
Hartford, Connecticut, 06106
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Clinical Study Site
Hermitage, Tennessee, 37129
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Clinical Study Site
Hialeah, Florida, 33013
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Clinical Study Site
Highlands Ranch, Colorado, 80129
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Clinical Study Site
Houston, Texas, 77026
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Clinical Study Site
Houston, Texas, 77030
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Clinical Study Site
Huntington Beach, California, 92648
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Clinical Study Site
Indianapolis, Indiana, 46202
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Clinical Study Site
Irvine, California, 92612
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Clinical Study Site
Irvine, California, 92618
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Clinical Study Site
Lebanon, New Hampshire, 03766
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Clinical Study Site
Lebanon, Pennsylvania, 17042
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Clinical Study Site
Lincoln, Nebraska, 68506
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Clinical Study Site
Lone Tree, Colorado, 80124
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Clinical Study Site
Los Angeles, California, 90027
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Clinical Study Site
Los Angeles, California, 90067
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Clinical Study Site
Los Angeles, California, 90404
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Clinical Study Site
Madison, Wisconsin, 53792
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Clinical Study Site
Mayfield Heights, Ohio, 44124
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Clinical Study Site
Miami, Florida, 33176
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Clinical Study Site
Miami Beach, Florida, 33140
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Clinical Study Site
Mineola, New York, 11501
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Clinical Study Site
Minneapolis, Minnesota, 55455
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Clinical Study Site
Mobile, Alabama, 36604
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Clinical Study Site
Murrieta, California, 92562
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Clinical Study Site
New Brunswick, New Jersey, 08901
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Clinical Study Site
New Haven, Connecticut, 06520-8028
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Clinical Study Site
New Orleans, Louisiana, 70121
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Clinical Study Site
New York, New York, 10016
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Clinical Study Site
Newark, Delaware, 19713
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Clinical Study Site
Newnan, Georgia, 30265
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Clinical Study Site
Newton, Massachusetts, 02462
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Clinical Study Site
Norwich, Connecticut, 06360
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Clinical Study Site
O'Fallon, Illinois, 62269
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Clinical Study Site
Oakland, California, 94611
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Clinical Study Site
Ocala, Florida, 34474
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Clinical Study Site
Oklahoma City, Oklahoma, 73120
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Clinical Study Site
Orange, California, 92868
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Clinical Study Site
Orlando, Florida, 32804
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Clinical Study Site
Orlando, Florida, 32806
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Clinical Study Site
Pasadena, California, 91030
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Clinical Study Site
Philadelphia, Pennsylvania, 19107
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Clinical Study Site
Philadelphia, Pennsylvania, 19111
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Clinical Study Site
Philadelphia, Pennsylvania, 19140
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Clinical Study Site
Pinehurst, North Carolina, 28374
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Clinical Study Site
Pittsburgh, Pennsylvania, 15212
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Clinical Study Site
Pittsburgh, Pennsylvania, 15232
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Clinical Study Site
Plantation, Florida, 33322
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Clinical Study Site
Port Saint Lucie, Florida, 34952
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Clinical Study Site
Providence, Rhode Island, 02903
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Clinical Study Site
Rochester, New York, 14642
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Clinical Study Site
Roseville, California, 95661
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Clinical Study Site
Saint Louis Park, Minnesota, 55426
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Clinical Study Site
Salt Lake City, Utah, 84106
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Clinical Study Site
Salt Lake City, Utah, 84112
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Clinical Study Site
San Francisco, California, 94115
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Clinical Study Site
Santa Clara, California, 94115
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Clinical Study Site
Sellersville, Pennsylvania, 18960
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Spartanburg, South Carolina, 29303
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Clinical Study Site
Spokane, Washington, 99208
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Clinical Study Site
Springfield, Missouri, 65804
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Clinical Study Site
St. Petersburg, Florida, 33705
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Clinical Study Site
Stanford, California, 94305
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Clinical Study Site
Syracuse, New York, 13210
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Tacoma, Washington, 98405
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Clinical Study Site
Tamarac, Florida, 33321
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Clinical Study Site
The Bronx, New York, 10461
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Clinical Study Site
Torrance, California, 90503
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Clinical Study Site
Tuscaloosa, Alabama, 35487
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Clinical Study Site
Tyler, Texas, 75701
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Clinical Study Site
Upland, California, 91786
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Clinical Study Site
Vallejo, California, 94589
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Clinical Study Site
West Hollywood, California, 90048
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Clinical Study Site
Westwood, Kansas, 66205
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Clinical Study Site
White Plains, New York, 10601-5000
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Other trials in United States

China31 sites, 31 recruiting

Clinical Study Site
Beijing, Beijing Municipality, 100020
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Clinical Study Site
Beijing, Beijing Municipality
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Clinical Study Site
Ch’ang-ch’un, Jilin, 130012
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Clinical Study Site
Changsha, Hunan, 410013
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Clinical Study Site
Chengdu, Sichuan, 610041
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Clinical Study Site
Chifeng, Inner Mongolia, 24000
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Clinical Study Site
Foshan, Guangdong, 528000
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Clinical Study Site
Fuzhou, Fujian, 350014
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Clinical Study Site
Fuzhou, Henan, 455000
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Clinical Study Site
Guangzhou, Fujian, 350004
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Clinical Study Site
Guangzhou, Guangdong, 510630
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Clinical Study Site
Haikou, Hainan, 570145
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Clinical Study Site
Hangzhou, Zhejiang, 310009
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Clinical Study Site
Hangzhou, Zhejiang, 310022
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Harbin, Heilongjiang, 150081
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Jinan, Shandong, 250021
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Kunming, Yunnan, 650118
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Clinical Study Site
Luzhou, Sichuan, 646000
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Clinical Study Site
Nanchang, Jiangxi, 330006
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Clinical Study Site
Nanjing, Jiangsu, 210009
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Clinical Study Site
Ningbo, Zhejiang, 315040
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Shanghai, Shanghai Municipality, 200032
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Clinical Study Site
Shenyang, Liaoning, 110001
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Clinical Study Site
Shenzhen, Guangdong, 518101
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Clinical Study Site
Shijiazhuang, Hebei, 50011
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Tianjin, Tianjin Municipality
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Clinical Study Site
Wenzhou, Zhejiang, 325000
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Clinical Study Site
Wuhan, Hubei, 430022
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Clinical Study Site
Yueyang, Hunan, 414020
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Clinical Study Site
Zhengzhou, Henan, 450052
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Clinical Study Site
Zhuhai, Guangdong
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Other trials in China

Japan18 sites, 18 recruiting

Clinical Study Site
Aichi, 464-8681
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Clinical Study Site
Chiba, 260-8717
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Clinical Study Site
Ehime, 791-0280
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Clinical Study Site
Fukuoka, 812-8582
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Clinical Study Site
Gifu, 501-1194
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Clinical Study Site
Hiroshima, 734-8551
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Clinical Study Site
Hokkaido, 060-8648
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Clinical Study Site
Kawasaki, 216-8511
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Clinical Study Site
Osaka, Ontario, 565-0871
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Clinical Study Site
Osaka, 541-8567
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Clinical Study Site
Saitama, 362-0806
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Clinical Study Site
Sendai, 980-0872
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Clinical Study Site
Shizuoka, 411-8777
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Clinical Study Site
Tokyo, 104-0045
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Clinical Study Site
Tokyo, 113-8677
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Clinical Study Site
Tokyo, 135-8550
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Clinical Study Site
Toyama, 930-0194
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Clinical Study Site
Yokohama, 241-8515
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Other trials in Japan

Spain18 sites, 18 recruiting

Clinical Study Site
A Coruña, 15006
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Clinical Study Site
Barcelona, 08035
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Clinical Study Site
Barcelona, 08036
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Clinical Study Site
Barcelona, 08908
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Clinical Study Site
Barcelona, 08916
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Clinical Study Site
Córdoba, 14004
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Clinical Study Site
Granada, 18014
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Clinical Study Site
Madrid, 28009
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Clinical Study Site
Madrid, 28046
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Clinical Study Site
Madrid, 28050
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Clinical Study Site
Madrid, 28222
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Clinical Study Site
Málaga, 29010
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Clinical Study Site
Palma de Mallorca, 07198
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Clinical Study Site
Santander, 39008
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Clinical Study Site
Seville, 41013
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Clinical Study Site
Valencia, 46010
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Clinical Study Site
Valencia, 46014
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Clinical Study Site
Valencia, 46026
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Other trials in Spain

France15 sites, 15 recruiting

Clinical Study Site
Bordeaux, 33076
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Clinical Study Site
Lille, 59000
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Clinical Study Site
Lyon, 69374
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Clinical Study Site
Marseille, 13009
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Clinical Study Site
Montpellier, 34298
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Clinical Study Site
Nancy
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Clinical Study Site
Nantes, 44000
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Clinical Study Site
Nice, 06189
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Clinical Study Site
Paris, 75015
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Clinical Study Site
Paris, 75020
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Clinical Study Site
Pierre-Bénite, 69495
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Clinical Study Site
Poitiers, 86000
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Clinical Study Site
Reims
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Clinical Study Site
Strasbourg, 67033
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Clinical Study Site
Villejuif, 94805
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Other trials in France

Italy9 sites, 9 recruiting

Clinical Study Site
Aviano, 33081
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Clinical Study Site
Brescia, 25124
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Clinical Study Site
Florence, 50134
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Clinical Study Site
Genova, 16132
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Clinical Study Site
Meldola, 47014
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Clinical Study Site
Milan, 20162
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Clinical Study Site
Pisa, 56126
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Clinical Study Site
Roma, Ontario, 00144
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Clinical Study Site
Verona, 37134
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Other trials in Italy

United Kingdom7 sites, 7 recruiting

Clinical Study Site
Aberdeen, Scotland, AB25 2ZN
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Clinical Study Site
Canterbury, England, CT13NS
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Clinical Study Site
Edinburgh, EH4 2XU
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Clinical Study Site
Liverpool, L7 8YA
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Clinical Study Site
London, England, EC1M 6BQ
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Clinical Study Site
Manchester, M20 4BX
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Clinical Study Site
Northwood, Middlesex
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Other trials in United Kingdom

Poland6 sites, 6 recruiting

Clinical Study Site
Gdansk, 80-219
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Clinical Study Site
Olsztyn, 10-228
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Clinical Study Site
Otwock, 05-400
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Clinical Study Site
Rzeszów, Podkarpackie Voivodeship, 35-021
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Clinical Study Site
Warsaw, 02-781
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Clinical Study Site
Warsaw, 04-141
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Other trials in Poland

Canada5 sites, 5 recruiting

Clinical Study Site
Brampton, Ontario, L6R 2J7
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Clinical Study Site
Montreal, Quebec, H4A 3J1
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Clinical Study Site
Regina, Saskatchewan, S4T7T1
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Clinical Study Site
Toronto, Ontario, M4N 3M5
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Clinical Study Site
Vancouver, British Columbia, V5Z 4E6
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Other trials in Canada

Czechia5 sites, 5 recruiting

Clinical Study Site
Brno, 60200
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Clinical Study Site
Hradec Králové, 50005
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Clinical Study Site
Olomouc, 779 00
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Clinical Study Site
Prague, 128 00
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Clinical Study Site
Prague, 14059
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Other trials in Czechia

Belgium4 sites, 4 recruiting

Clinical Study Site
Brussels, 1000
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Clinical Study Site
Ghent, 9000
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Clinical Study Site
Haine-Saint-Paul, 7100
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Clinical Study Site
Kortrijk, 8500
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Other trials in Belgium

Germany4 sites, 4 recruiting

Clinical Study Site
Berlin, 13353
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Clinical Study Site
Bonn, 53113
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Clinical Study Site
Hamburg, 20249
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Clinical Study Site
Hamburg, 22763
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Other trials in Germany

Hungary4 sites, 4 recruiting

Clinical Study Site
Budapest, 1122
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Clinical Study Site
Budapest
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Clinical Study Site
Debrecen, 4032
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Clinical Study Site
Kecskemét, H-6000
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Other trials in Hungary

Mexico4 sites, 4 recruiting

Clinical Study Site
Aguas Calientes, 20124
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Clinical Study Site
Mexico City, 06100
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Clinical Study Site
Monterrey, 64710
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Clinical Study Site
Oaxaca City, 68020
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Other trials in Mexico

Puerto Rico1 site, 1 recruiting

Clinical Study Site
Rio Piedras, 00935
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Other trials in Puerto Rico

About this study

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

Read the detailed 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.

Conditions: Metastatic Colorectal Cancer (CRC)
Being tested: Drug: Ivonescimab Injection, Drug: Bevacizumab Injection
Keywords: mCRC, Ivonescimab
Medical subject headings: Colorectal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Drug: Ivonescimab InjectionDrug
Also called Oxaliplatin, Leucovorin, 5-Fluorouracil
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.
Drug: Bevacizumab InjectionDrug
Also called Oxaliplatin, Leucovorin, 5-Fluorouracil
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.

Study groups in NCT07228832
Study group	Role	What they receive
Arm A: Ivonescimab in combination with mFOLFOX6	Experimental	Subjects will receive Ivonescimab Plus mFOLFOX6 via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-FU will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years. Receives: Drug: Drug: Ivonescimab Injection
Arm B: Bevacizumab in combination with mFOLFOX6	Active comparator	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. Receives: Drug: Drug: Bevacizumab Injection

What is being measured

The primary outcome is the main question the study is designed to answer.

PFS by IRRC based on RECIST v1.1
Progression-free survival (PFS) assessed by IRRC per RECIST v1.1
Measured: Up to approximately 2.5 years

Secondary outcomes (4)

Overall Survival (OS) in the population
Overall Survival (OS) in the mCRC population
Measured: Up to approximately 4 years
ORR
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
Measured: Up to approximately 2.5 years
Adverse Events (AE)
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]
Measured: Up to approximately 4 years
DoR
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
Measured: up to approximately 2.5 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

18 Nov 202530 Nov 2029

First posted14 Nov 2025
Study start18 Nov 2025
Primary completion31 May 2028 (estimated)
Study completion30 Nov 2029 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Metastatic Colorectal Cancer (CRC)Studies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 900 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT07228832
Sponsor's protocol ID: SMT112-3005
Acronym: HARMONi-GI3
Status last verified: Nov 2026
First submitted: 10 Nov 2025
Last updated: 5 Nov 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

Interested in taking part?

Ning Chang, MD

1-833-256-0522

medicalaffairs@summitplc.com

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See sites and contacts

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Hepatic Artery Infusion of Carfilzomib in Participants With Liver Metastatic Disease Previously Treated With Hepatic Artery Infusion Pump Therapy
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Metastatic Colorectal Cancer
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SAMe in Prevention of Oxaliplatin-associated Liver Injury
Colorectal Cancer, Liver Metastases
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A Study of ERAS-0015 in Patients With Advanced or Metastatic Solid Tumors
Metastatic Solid Tumors
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A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
CRC

All Metastatic Colorectal Cancer (CRC) trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

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
ClinicalTrials.gov ID: NCT07228832
Acronym / sponsor ID: HARMONi-GI3 / SMT112-3005
Conditions: Metastatic Colorectal Cancer (CRC)
Keywords: mCRC, Ivonescimab
Phase: Phase 3
Study type: Interventional
Recruitment status: Recruiting
Enrolment: 900 participants (estimated)
Lead sponsor: Summit TherapeuticsIndustry (pharma, biotech, devices)
Study start: 18 Nov 2025 (actual)
Primary completion: 31 May 2028 (estimated)
Study completion: 30 Nov 2029 (estimated)
First posted: 14 Nov 2025 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Arm A: Ivonescimab in combination with mFOLFOX6	Experimental	Drug: Drug: Ivonescimab InjectionSubjects will receive Ivonescimab Plus mFOLFOX6 via intravenous infusion (IV) Q2W, up to 8 cycles. Afterward, Ivonescimab plus Leucovorin and 5-FU will be used for maintenance treatment (administered on Day 1 of each cycle, Q2W) up to 2 years.
Arm B: Bevacizumab in combination with mFOLFOX6	Active comparator	Drug: Drug: Bevacizumab InjectionSubjects 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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

Key exclusion criteria (7 listed)

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

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Drug: Ivonescimab InjectionAlso: Oxaliplatin, Leucovorin, 5-FluorouracilSubjects 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.	Drug	Arm A: Ivonescimab in combination with mFOLFOX6
Drug: Bevacizumab InjectionAlso: Oxaliplatin, Leucovorin, 5-FluorouracilSubjects 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.	Drug	Arm B: Bevacizumab in combination with mFOLFOX6

Primary outcome

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

4 secondary outcomes

Overall Survival (OS) in the population
Time frame: Up to approximately 4 years
ORR
Time frame: Up to approximately 2.5 years
Adverse Events (AE)
Time frame: Up to approximately 4 years
DoR
Time frame: up to approximately 2.5 years

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Nov 2026.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.

Ning Chang, MD contact

1-833-256-0522

medicalaffairs@summitplc.com

243 sites in 15 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Drug: Ivonescimab Injection and Drug: Bevacizumab Injection in people with Metastatic Colorectal Cancer (CRC), run by Summit Therapeutics at 243 sites in 15 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 5 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 243 sites in United States, China, Japan, Spain, France and 10 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Ning Chang, MD (1-833-256-0522, medicalaffairs@summitplc.com), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

PFS by IRRC based on RECIST v1.1 (time frame: Up to approximately 2.5 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT07228832.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Nov 2026.