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RecruitingInterventionalPhase 3

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

NCT ID: NCT07228832Sponsor: Summit TherapeuticsLast updated: 2026-06-17

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)

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.

Arms & interventions

  • DrugDrug: 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.

  • DrugDrug: 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.

Outcome measures

Primary

  • PFS by IRRC based on RECIST v1.1

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

    Time frame: Up to approximately 2.5 years

Secondary

  • 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

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (58)

Clinical Study Site

Goodyear, Arizona, 85338

Recruiting

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

Cerritos, California, 90703

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Clinical Study Site

Corona, California, 92882

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Clinical Study Site

Duarte, California, 91010

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Clinical Study Site

Fountain Valley, California, 92708

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Clinical Study Site

Huntington Beach, California, 92648

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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

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

Murrieta, California, 92562

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Clinical Study Site

Orange, California, 92868

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Clinical Study Site

Pasadena, California, 91030

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Clinical Study Site

Torrance, California, 90503

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Clinical Study Site

Upland, California, 91786

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Clinical Study Site

West Hollywood, California, 90048

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Clinical Study Site

Hartford, Connecticut, 06106

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Clinical Study Site

New Haven, Connecticut, 06520-8028

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Clinical Study Site

Norwich, Connecticut, 06360

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Clinical Study Site

Hialeah, Florida, 33013

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Clinical Study Site

Miami, Florida, 33176

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Clinical Study Site

Orlando, Florida, 32806

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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

Tamarac, Florida, 33321

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Clinical Study Site

Newnan, Georgia, 30265

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Clinical Study Site

Chicago, Illinois, 60611

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Clinical Study Site

Elmhurst, Illinois, 60540

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Clinical Study Site

O'Fallon, Illinois, 62269

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Clinical Study Site

Fort Wayne, Indiana, 46804

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Clinical Study Site

Indianapolis, Indiana, 46202

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Clinical Study Site

Edgewood, Kentucky, 41017

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Clinical Study Site

Saint Louis Park, Minnesota, 55426

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Clinical Study Site

Billings, Montana, 59102

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Clinical Study Site

Lincoln, Nebraska, 68506

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Clinical Study Site

New Brunswick, New Jersey, 08901

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Clinical Study Site

Mineola, New York, 11501

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Clinical Study Site

New York, New York, 10016

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Clinical Study Site

The Bronx, New York, 10461

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Clinical Study Site

Akron, Ohio, 44032

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Clinical Study Site

Canton, Ohio, 44703

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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

Mayfield Heights, Ohio, 44124

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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

Hermitage, Tennessee, 37129

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Clinical Study Site

Fort Worth, Texas, 76104

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Clinical Study Site

Salt Lake City, Utah, 84106

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Clinical Study Site

Charlottesville, Virginia, 22908

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Clinical Study Site

Spokane, Washington, 99208

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Clinical Study Site

Tacoma, Washington, 98405

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Clinical Study Site

Charleston, West Virginia, 25304

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