Recruiting
Phase 3

Ivonescimab & mFOLFOX6

Sponsor:

Summit Therapeutics

Code:

NCT07228832

Conditions

Metastatic Colorectal Cancer (CRC)

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Drug: Ivonescimab Injection

Drug: Bevacizumab Injection

Study Details

Brief 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)

Conditions

Metastatic Colorectal Cancer (CRC)

Study ID

NCT07228832

Start date

Nov 18, 2025

Status verified date

Sep, 2026

Completion date

Nov 30, 2029

Anticipated

Primary completion date

May 31, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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

Study Design

Enrollment

600 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Arm A: Ivonescimab in combination with mFOLFOX6

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.

active comparator: Arm B: Bevacizumab in combination with mFOLFOX6

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.

Interventions

Drug: 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.

Drug: 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.

Primary outcome measure

  • PFS by IRRC based on RECIST v1.1 [ Time Frame: Up to approximately 2.5 years ]

Central Contacts and Locations

Central contacts

Ning Chang, MD

1-833-256-0522medicalaffairs@summitplc.com

Locations

Clinical Study Site

Recruiting

Mobile, Alabama, United States, 36604

Clinical Study Site

Recruiting

Tuscaloosa, Alabama, United States, 35487

Clinical Study Site

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Goodyear, Arizona, United States, 85338

Clinical Study Site

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Beverly Hills, California, United States, 90211

Clinical Study Site

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Beverly Hills, California, United States, 90212

Clinical Study Site

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Cerritos, California, United States, 90703

Clinical Study Site

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Corona, California, United States, 92882

Clinical Study Site

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Duarte, California, United States, 91010

Clinical Study Site

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Fountain Valley, California, United States, 92708

Clinical Study Site

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Huntington Beach, California, United States, 92648

Clinical Study Site

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Irvine, California, United States, 92612

Clinical Study Site

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Irvine, California, United States, 92618

Clinical Study Site

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Los Angeles, California, United States, 90027

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Los Angeles, California, United States, 90067

Clinical Study Site

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Los Angeles, California, United States, 90404

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Murrieta, California, United States, 92562

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Oakland, California, United States, 94611

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Orange, California, United States, 92868

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Pasadena, California, United States, 91030

Clinical Study Site

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Roseville, California, United States, 95661

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San Francisco, California, United States, 94115

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Santa Clara, California, United States, 94115

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Stanford, California, United States, 94305

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Torrance, California, United States, 90503

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Upland, California, United States, 91786

Clinical Study Site

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Vallejo, California, United States, 94589

Clinical Study Site

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West Hollywood, California, United States, 90048

Clinical Study Site

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Hartford, Connecticut, United States, 06106

Clinical Study Site

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New Haven, Connecticut, United States, 06520-8028

Clinical Study Site

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Norwich, Connecticut, United States, 06360

Clinical Study Site

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Newark, Delaware, United States, 19713

Clinical Study Site

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Hialeah, Florida, United States, 33013

Clinical Study Site

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Miami, Florida, United States, 33176

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Miami Beach, Florida, United States, 33140

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Ocala, Florida, United States, 34474

Clinical Study Site

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Orlando, Florida, United States, 32804

Clinical Study Site

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Orlando, Florida, United States, 32806

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Plantation, Florida, United States, 33322

Clinical Study Site

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Port Saint Lucie, Florida, United States, 34952

Clinical Study Site

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St. Petersburg, Florida, United States, 33705

Clinical Study Site

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Tamarac, Florida, United States, 33321

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Atlanta, Georgia, United States, 30303

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Atlanta, Georgia, United States, 30322

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Newnan, Georgia, United States, 30265

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Chicago, Illinois, United States, 60611

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Elmhurst, Illinois, United States, 60540

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O'Fallon, Illinois, United States, 62269

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Fort Wayne, Indiana, United States, 46804

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Indianapolis, Indiana, United States, 46202

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Westwood, Kansas, United States, 66205

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Edgewood, Kentucky, United States, 41017

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New Orleans, Louisiana, United States, 70121

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Baltimore, Maryland, United States, 21201

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Detroit, Michigan, United States, 48201

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Saint Louis Park, Minnesota, United States, 55426

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Springfield, Missouri, United States, 65804

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Billings, Montana, United States, 59102

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Lincoln, Nebraska, United States, 68506

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Lebanon, New Hampshire, United States, 03766

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New Brunswick, New Jersey, United States, 08901

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Mineola, New York, United States, 11501

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New York, New York, United States, 10016

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Rochester, New York, United States, 14642

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Syracuse, New York, United States, 13210

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The Bronx, New York, United States, 10461

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White Plains, New York, United States, 10601-5000

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Pinehurst, North Carolina, United States, 28374

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Akron, Ohio, United States, 44032

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Canton, Ohio, United States, 44703

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Cincinnati, Ohio, United States, 45219

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Cincinnati, Ohio, United States, 45220

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Cleveland, Ohio, United States, 44111

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Cleveland, Ohio, United States, 44195

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Mayfield Heights, Ohio, United States, 44124

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Oklahoma City, Oklahoma, United States, 73120

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Lebanon, Pennsylvania, United States, 17042

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Philadelphia, Pennsylvania, United States, 19107

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Philadelphia, Pennsylvania, United States, 19111

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Philadelphia, Pennsylvania, United States, 19140

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Pittsburgh, Pennsylvania, United States, 15212

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Pittsburgh, Pennsylvania, United States, 15232

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Sellersville, Pennsylvania, United States, 18960

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Providence, Rhode Island, United States, 02903

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Greenville, South Carolina, United States, 29605

Clinical Study Site

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Spartanburg, South Carolina, United States, 29303

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Germantown, Tennessee, United States, 38138

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Hermitage, Tennessee, United States, 37129

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Dallas, Texas, United States, 75235

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Dallas, Texas, United States, 75390

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Fort Worth, Texas, United States, 76104

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Houston, Texas, United States, 77026

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Houston, Texas, United States, 77030

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Tyler, Texas, United States, 75701

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Salt Lake City, Utah, United States, 84106

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Salt Lake City, Utah, United States, 84112

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Burlington, Vermont, United States, 05401

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Charlottesville, Virginia, United States, 22908

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Fairfax, Virginia, United States, 22031

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Spokane, Washington, United States, 99208

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Tacoma, Washington, United States, 98405

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Charleston, West Virginia, United States, 25304

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Madison, Wisconsin, United States, 53792

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Toronto, Ontario, Canada, M4N 3M5

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Montreal, Quebec, Canada, H4A 3J1

Clinical Study Site

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Regina, Saskatchewan, Canada, S4T7T1

More Information

Sponsor

Summit Therapeutics

Last update posted

Sep 2, 2026

Last verified

Sep, 2026

Keywords

  • mCRC
  • Ivonescimab

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Summit Therapeutics on 2026-09-02.