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

Recruitment Status
RECRUITING
(See Contacts and Locations)Verified April 2026 by Summit Therapeutics
Sponsor
Summit Therapeutics
Information Provided by (Responsible Party)
Summit Therapeutics
Clinicaltrials.gov Identifier
NCT07228832
Other Study ID Numbers:
SMT112-3005
First Submitted
November 9, 2025
First Posted
November 13, 2025
Last Update Posted
May 4, 2026
Last Verified
April 2026

ClinicalTrials.gov processed this data on April 2026. Link to the current ClinicalTrials.gov record .

History of Changes

Study Details

Study 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.

Condition or DiseaseIntervention/Treatment
Metastatic Colorectal Cancer (CRC)
Drug: Drug: Ivonescimab InjectionDrug: Drug: Bevacizumab Injection

Study Design

Study TypeInterventional
Actual Enrollment600 participants
Design AllocationRandomized
Interventional ModelParallel Assignment
MaskingQuadruple
Primary PurposeTreatment
Official TitleA 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
Study Start DateNovember 17, 2025
Actual Primary Completion Date2yrs 3w from now
Actual Study Completion Date3yrs 6mos from now

Groups and Cohorts

Group/CohortIntervention/Treatment
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.
Drug: 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.
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.
Drug: 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.

Outcome Measures

Primary Outcome Measures
  1. PFS by IRRC based on RECIST v1.1
    Progression-free survival (PFS) assessed by IRRC per RECIST v1.1
Secondary Outcome Measures
  1. Overall Survival (OS) in the population
    Overall Survival (OS) in the mCRC population
  2. 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
  3. Adverse Events (AE)
    incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results \[From the time subject signs the ICF to 30 days (AE) and 90 days (SAE related to ivonescimab/bevacizumab) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first\]
  4. 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

Eligibility Criteria

Ages Eligible for Study(Adult, Older Adult)
Sexes Eligible for StudyAll
Accepts Healthy VolunteersNo
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

Contacts and Locations

Sponsors and CollaboratorsSummit Therapeutics
Locations
Clinical Study Site | Goodyear Arizona, United States, 85338Clinical Study Site | Beverly Hills California, United States, 90211Clinical Study Site | Beverly Hills California, United States, 90212Clinical Study Site | Cerritos California, United States, 90703Clinical Study Site | Corona California, United States, 92882Clinical Study Site | Duarte California, United States, 91010Clinical Study Site | Fountain Valley California, United States, 92708Clinical Study Site | Huntington Beach California, United States, 92648Clinical Study Site | Irvine California, United States, 92612Clinical Study Site | Irvine California, United States, 92618Clinical Study Site | Los Angeles California, United States, 90027Clinical Study Site | Los Angeles California, United States, 90067Clinical Study Site | Los Angeles California, United States, 90404Clinical Study Site | Murrieta California, United States, 92562Clinical Study Site | Orange California, United States, 92868Clinical Study Site | Pasadena California, United States, 91030Clinical Study Site | Torrance California, United States, 90503Clinical Study Site | Upland California, United States, 91786Clinical Study Site | West Hollywood California, United States, 90048Clinical Study Site | Hartford Connecticut, United States, 06106Clinical Study Site | New Haven Connecticut, United States, 06520-8028Clinical Study Site | Norwich Connecticut, United States, 06360Clinical Study Site | Hialeah Florida, United States, 33013Clinical Study Site | Miami Florida, United States, 33176Clinical Study Site | Orlando Florida, United States, 32806Clinical Study Site | Plantation Florida, United States, 33322Clinical Study Site | Port Saint Lucie Florida, United States, 34952Clinical Study Site | Tamarac Florida, United States, 33321Clinical Study Site | Newnan Georgia, United States, 30265Clinical Study Site | Chicago Illinois, United States, 60611Clinical Study Site | Elmhurst Illinois, United States, 60540Clinical Study Site | O'Fallon Illinois, United States, 62269Clinical Study Site | Fort Wayne Indiana, United States, 46804Clinical Study Site | Indianapolis Indiana, United States, 46202Clinical Study Site | Edgewood Kentucky, United States, 41017Clinical Study Site | Saint Louis Park Minnesota, United States, 55426Clinical Study Site | Billings Montana, United States, 59102Clinical Study Site | Lincoln Nebraska, United States, 68506Clinical Study Site | New Brunswick New Jersey, United States, 08901Clinical Study Site | Mineola New York, United States, 11501Clinical Study Site | New York New York, United States, 10016Clinical Study Site | The Bronx New York, United States, 10461Clinical Study Site | Akron Ohio, United States, 44032Clinical Study Site | Canton Ohio, United States, 44703Clinical Study Site | Cincinnati Ohio, United States, 45219Clinical Study Site | Cincinnati Ohio, United States, 45220Clinical Study Site | Cleveland Ohio, United States, 44111Clinical Study Site | Cleveland Ohio, United States, 44195Clinical Study Site | Mayfield Heights Ohio, United States, 44124Clinical Study Site | Philadelphia Pennsylvania, United States, 19111Clinical Study Site | Philadelphia Pennsylvania, United States, 19140Clinical Study Site | Hermitage Tennessee, United States, 37129Clinical Study Site | Fort Worth Texas, United States, 76104Clinical Study Site | Salt Lake City Utah, United States, 84106Clinical Study Site | Charlottesville Virginia, United States, 22908Clinical Study Site | Spokane Washington, United States, 99208Clinical Study Site | Tacoma Washington, United States, 98405Clinical Study Site | Charleston West Virginia, United States, 25304Clinical Study Site | Montreal Quebec, Canada, H4A 3J1Clinical Study Site | Aichi , Japan, 464-8681Clinical Study Site | Chiba , Japan, 260-8717Clinical Study Site | Fukuoka , Japan, 812-8582Clinical Study Site | Gifu , Japan, 501-1194Clinical Study Site | Hiroshima , Japan, 734-8551Clinical Study Site | Hokkaido , Japan, 060-8648Clinical Study Site | Kawasaki , Japan, 216-8511Clinical Study Site | Osaka , Japan, 541-8567Clinical Study Site | Sendai , Japan, 980-0872Clinical Study Site | Shizuoka , Japan, 411-8777Clinical Study Site | Tokyo , Japan, 104-0045Clinical Study Site | Tokyo , Japan, 135-8550Clinical Study Site | Toyama , Japan, 930-0194Clinical Study Site | Rio Piedras , Puerto Rico, 00935Clinical Study Site | Canterbury England, United Kingdom, CT13NSClinical Study Site | London England, United Kingdom, EC1M 6BQClinical Study Site | Aberdeen Scotland, United Kingdom, AB25 2ZN