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: 5 countries
• Sites: 76

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 (76)

Clinical Study Site

Goodyear, Arizona, 85338, United States

RECRUITING

Clinical Study Site

Beverly Hills, California, 90211, United States

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Clinical Study Site

Beverly Hills, California, 90212, United States

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Clinical Study Site

Cerritos, California, 90703, United States

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Clinical Study Site

Corona, California, 92882, United States

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Clinical Study Site

Duarte, California, 91010, United States

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Clinical Study Site

Fountain Valley, California, 92708, United States

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Clinical Study Site

Huntington Beach, California, 92648, United States

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Clinical Study Site

Irvine, California, 92612, United States

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Clinical Study Site

Irvine, California, 92618, United States

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Los Angeles, California, 90027, United States

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Clinical Study Site

Los Angeles, California, 90067, United States

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Clinical Study Site

Los Angeles, California, 90404, United States

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Clinical Study Site

Murrieta, California, 92562, United States

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Clinical Study Site

Orange, California, 92868, United States

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Clinical Study Site

Pasadena, California, 91030, United States

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Clinical Study Site

Torrance, California, 90503, United States

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Clinical Study Site

Upland, California, 91786, United States

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Clinical Study Site

West Hollywood, California, 90048, United States

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Clinical Study Site

Hartford, Connecticut, 06106, United States

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Clinical Study Site

New Haven, Connecticut, 06520-8028, United States

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Clinical Study Site

Norwich, Connecticut, 06360, United States

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Clinical Study Site

Hialeah, Florida, 33013, United States

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Clinical Study Site

Miami, Florida, 33176, United States

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Clinical Study Site

Orlando, Florida, 32806, United States

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Clinical Study Site

Plantation, Florida, 33322, United States

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Clinical Study Site

Port Saint Lucie, Florida, 34952, United States

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Clinical Study Site

Tamarac, Florida, 33321, United States

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Clinical Study Site

Newnan, Georgia, 30265, United States

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Clinical Study Site

Chicago, Illinois, 60611, United States

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Clinical Study Site

Elmhurst, Illinois, 60540, United States

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Clinical Study Site

O'Fallon, Illinois, 62269, United States

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Clinical Study Site

Fort Wayne, Indiana, 46804, United States

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Clinical Study Site

Indianapolis, Indiana, 46202, United States

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Clinical Study Site

Edgewood, Kentucky, 41017, United States

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Clinical Study Site

Saint Louis Park, Minnesota, 55426, United States

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Billings, Montana, 59102, United States

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Clinical Study Site

Lincoln, Nebraska, 68506, United States

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Clinical Study Site

New Brunswick, New Jersey, 08901, United States

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Clinical Study Site

Mineola, New York, 11501, United States

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Clinical Study Site

New York, New York, 10016, United States

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Clinical Study Site

The Bronx, New York, 10461, United States

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Clinical Study Site

Akron, Ohio, 44032, United States

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Clinical Study Site

Canton, Ohio, 44703, United States

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Clinical Study Site

Cincinnati, Ohio, 45219, United States

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Clinical Study Site

Cincinnati, Ohio, 45220, United States

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Clinical Study Site

Cleveland, Ohio, 44111, United States

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Clinical Study Site

Cleveland, Ohio, 44195, United States

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Clinical Study Site

Mayfield Heights, Ohio, 44124, United States

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Clinical Study Site

Philadelphia, Pennsylvania, 19111, United States

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Clinical Study Site

Philadelphia, Pennsylvania, 19140, United States

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Clinical Study Site

Hermitage, Tennessee, 37129, United States

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Clinical Study Site

Fort Worth, Texas, 76104, United States

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Clinical Study Site

Salt Lake City, Utah, 84106, United States

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Clinical Study Site

Charlottesville, Virginia, 22908, United States

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Clinical Study Site

Spokane, Washington, 99208, United States

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Clinical Study Site

Tacoma, Washington, 98405, United States

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Clinical Study Site

Charleston, West Virginia, 25304, United States

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Clinical Study Site

Montreal, Quebec, H4A 3J1, Canada

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Clinical Study Site

Aichi, 464-8681, Japan

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Clinical Study Site

Chiba, 260-8717, Japan

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Clinical Study Site

Fukuoka, 812-8582, Japan

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Clinical Study Site

Gifu, 501-1194, Japan

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Clinical Study Site

Hiroshima, 734-8551, Japan

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Clinical Study Site

Hokkaido, 060-8648, Japan

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Clinical Study Site

Kawasaki, 216-8511, Japan

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Clinical Study Site

Osaka, 541-8567, Japan

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Clinical Study Site

Sendai, 980-0872, Japan

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Clinical Study Site

Shizuoka, 411-8777, Japan

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Clinical Study Site

Tokyo, 104-0045, Japan

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Clinical Study Site

Tokyo, 135-8550, Japan

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Clinical Study Site

Toyama, 930-0194, Japan

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Clinical Study Site

Rio Piedras, 00935, Puerto Rico

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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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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

Nindhana Paranthaman, 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: May 5, 2026

Record last verified: 2026-05

Locations

US (58); GB (3); JP (13); PR (1); CA (1)