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

NCT07228832 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: SMT112-3005
• Study Type: interventional
• Target: 600
• Locations: 12 countries
• Sites: 140

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)

Keywords

mCRC; Ivonescimab

Outcome Measures

Primary Outcomes (1)

• PFS by IRRC based on RECIST v1.1

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

  Up to approximately 2.5 years

Secondary Outcomes (4)

• Overall Survival (OS) in the population

  Up to approximately 4 years

• ORR

  Up to approximately 2.5 years

• Adverse Events (AE)

  Up to approximately 4 years

• DoR

  up to approximately 2.5 years

Study Arms (2)

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.

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.

Drug: Drug: Bevacizumab Injection

Interventions

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.

Also known as: Oxaliplatin, Leucovorin, 5-Fluorouracil

Arm A: Ivonescimab in combination with mFOLFOX6

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.

Also known as: Oxaliplatin, Leucovorin, 5-Fluorouracil

Arm B: Bevacizumab in combination with mFOLFOX6

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Summit Therapeutics: lead

Study Sites (140)

Clinical Study Site

Mobile, Alabama, 36604, United States

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Tuscaloosa, Alabama, 35487, United States

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Goodyear, Arizona, 85338, United States

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Beverly Hills, California, 90211, United States

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Beverly Hills, California, 90212, United States

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Cerritos, California, 90703, United States

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Corona, California, 92882, United States

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Duarte, California, 91010, United States

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Fountain Valley, California, 92708, United States

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Huntington Beach, California, 92648, United States

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Irvine, California, 92612, United States

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Irvine, California, 92618, United States

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Los Angeles, California, 90027, United States

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Los Angeles, California, 90067, United States

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Los Angeles, California, 90404, United States

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Murrieta, California, 92562, United States

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Orange, California, 92868, United States

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Pasadena, California, 91030, United States

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Torrance, California, 90503, United States

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Upland, California, 91786, United States

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West Hollywood, California, 90048, United States

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Hartford, Connecticut, 06106, United States

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New Haven, Connecticut, 06520-8028, United States

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Norwich, Connecticut, 06360, United States

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Newark, Delaware, 19713, United States

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Hialeah, Florida, 33013, United States

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Miami, Florida, 33176, United States

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Orlando, Florida, 32806, United States

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Plantation, Florida, 33322, United States

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Port Saint Lucie, Florida, 34952, United States

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St. Petersburg, Florida, 33705, United States

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Tamarac, Florida, 33321, United States

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Atlanta, Georgia, 30303, United States

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Atlanta, Georgia, 30322, United States

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Newnan, Georgia, 30265, United States

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Chicago, Illinois, 60611, United States

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Elmhurst, Illinois, 60540, United States

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O'Fallon, Illinois, 62269, United States

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Fort Wayne, Indiana, 46804, United States

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Indianapolis, Indiana, 46202, United States

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Westwood, Kansas, 66205, United States

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Edgewood, Kentucky, 41017, United States

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New Orleans, Louisiana, 70121, United States

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Baltimore, Maryland, 21201, United States

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Detroit, Michigan, 48201, United States

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Saint Louis Park, Minnesota, 55426, United States

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Springfield, Missouri, 65804, United States

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Billings, Montana, 59102, United States

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Lincoln, Nebraska, 68506, United States

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Lebanon, New Hampshire, 03766, United States

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New Brunswick, New Jersey, 08901, United States

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Mineola, New York, 11501, United States

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New York, New York, 10016, United States

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Rochester, New York, 14642, United States

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Syracuse, New York, 13210, United States

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The Bronx, New York, 10461, United States

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

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Akron, Ohio, 44032, United States

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Canton, Ohio, 44703, United States

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Cincinnati, Ohio, 45219, United States

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Cincinnati, Ohio, 45220, United States

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Cleveland, Ohio, 44111, United States

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Cleveland, Ohio, 44195, United States

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Mayfield Heights, Ohio, 44124, United States

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Oklahoma City, Oklahoma, 73120, United States

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Lebanon, Pennsylvania, 17042, United States

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Philadelphia, Pennsylvania, 19111, United States

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Philadelphia, Pennsylvania, 19140, United States

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Pittsburgh, Pennsylvania, 15212, United States

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Providence, Rhode Island, 02903, United States

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Greenville, South Carolina, 29605, United States

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Hermitage, Tennessee, 37129, United States

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Dallas, Texas, 75235, United States

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Dallas, Texas, 75390, United States

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Fort Worth, Texas, 76104, United States

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Tyler, Texas, 75701, United States

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Salt Lake City, Utah, 84106, United States

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Charlottesville, Virginia, 22908, United States

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Fairfax, Virginia, 22031, United States

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Spokane, Washington, 99208, United States

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Tacoma, Washington, 98405, United States

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Charleston, West Virginia, 25304, United States

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Madison, Wisconsin, 53792, United States

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Brussels, 1000, Belgium

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Ghent, 9000, Belgium

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Haine-Saint-Paul, 7100, Belgium

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Kortrijk, 8500, Belgium

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Toronto, Ontario, M4N 3M5, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Regina, Saskatchewan, S4T7T1, Canada

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Hradec Králové, 50005, Czechia

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Prague, 14059, Czechia

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Lyon, 69374, France

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Montpellier, 34298, France

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Nantes, 44000, France

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Paris, 75015, France

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Paris, 75020, France

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Pierre-Bénite, 69495, France

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Poitiers, 86000, France

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Strasbourg, 67033, France

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Bonn, 53113, Germany

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Hamburg, 20249, Germany

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Hamburg, 22763, Germany

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Meldola, 47014, Italy

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Osaka, Ontario, 565-0871, Japan

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Aichi, 464-8681, Japan

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Chiba, 260-8717, Japan

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Ehime, 791-0280, Japan

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Fukuoka, 812-8582, Japan

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Gifu, 501-1194, Japan

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Hiroshima, 734-8551, Japan

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Hokkaido, 060-8648, Japan

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Kawasaki, 216-8511, Japan

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Osaka, 541-8567, Japan

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Saitama, 362-0806, Japan

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Sendai, 980-0872, Japan

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Shizuoka, 411-8777, Japan

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Tokyo, 104-0045, Japan

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Tokyo, 135-8550, Japan

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Toyama, 930-0194, Japan

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Yokohama, 241-8515, Japan

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Rzeszów, Podkarpackie Voivodeship, 35-021, Poland

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Warsaw, 04-141, Poland

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Clinical Study Site

Rio Piedras, 00935, Puerto Rico

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A Coruña, 15006, Spain

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Barcelona, 08035, Spain

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Barcelona, 08908, Spain

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Madrid, 28009, Spain

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Madrid, 28046, Spain

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Madrid, 28050, Spain

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Clinical Study Site

Palma de Mallorca, 07198, Spain

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Clinical Study Site

Santander, 39008, Spain

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Valencia, 46010, Spain

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Clinical Study Site

Valencia, 46014, Spain

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Clinical Study Site

Valencia, 46026, Spain

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Clinical Study Site

Canterbury, England, CT13NS, United Kingdom

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Clinical Study Site

London, England, EC1M 6BQ, United Kingdom

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Clinical Study Site

Aberdeen, Scotland, AB25 2ZN, United Kingdom

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Clinical Study Site

Edinburgh, EH4 2XU, United Kingdom

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Clinical Study Site

Manchester, M20 4BX, United Kingdom

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MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Oxaliplatin; Leucovorin; Fluorouracil; Bevacizumab

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Central Study Contacts

Ning Chang, MD

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2025
• First Posted: November 14, 2025
• Study Start: November 18, 2025
• Primary Completion (Estimated): May 31, 2028
• Study Completion (Estimated): November 30, 2029
• Last Updated: July 6, 2026

Record last verified: 2026-07

Locations

US (83); CZ (2); FR (8); DE (3); ES (11); PL (2); BE (4); GB (5); CA (3); PR (1); JP (17); IT (1)