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)
Brief Title
Phase III Study of Ivonescimab or Bevacizumab Combined With FOLFOX in Patients With Metastatic Colorectal Cancer
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.
Central Contacts
Central Contact Role
Contact
Central Contact Phone
1-833-256-0522
Central Contact Email
medicalaffairs@summitplc.com
Completion Date
Completion Date Type
Estimated
Conditions
Metastatic Colorectal Cancer (CRC)
Eligibility Criteria
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
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
Inclusion Criteria
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
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
Gender
All
Gender Based
false
Keywords
mCRC
Ivonescimab
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT07228832
Org Class
Industry
Org Full Name
Summit Therapeutics
Org Study Id
SMT112-3005
Overall Status
Recruiting
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Estimated
Official Title
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
Primary Outcomes
Outcome Description
Progression-free survival (PFS) assessed by IRRC per RECIST v1.1
Outcome Measure
PFS by IRRC based on RECIST v1.1
Outcome Time Frame
Up to approximately 2.5 years
Secondary Outcomes
Outcome Description
Overall Survival (OS) in the mCRC population
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Overall Survival (OS) in the population
Outcome Description
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
Outcome Time Frame
Up to approximately 2.5 years
Outcome Measure
ORR
Outcome Description
incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results \[From the time subject signs the ICF to 30 days (AE) and 90 days (SAE related to ivonescimab/bevacizumab) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first\]
Outcome Time Frame
Up to approximately 4 years
Outcome Measure
Adverse Events (AE)
Outcome Description
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
Outcome Time Frame
up to approximately 2.5 years
Outcome Measure
DoR
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Actual
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
Fernand Bteich
Investigator Department
Medicine
Investigator Division
Oncology
Investigator Sponsor Organization
External
Study Department
Oncology (Medical/Hematologic)
Study Division
Medical and Hematologic Oncology
Categories Mesh Debug
Colorectal Cancer --- COLORECTAL NEOPLASMS
Gastrointestinal (GI) Cancers --- COLORECTAL NEOPLASMS
Gastrointestinal (GI) Cancers --- INTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- GASTROINTESTINAL NEOPLASMS
Gastrointestinal (GI) Cancers --- DIGESTIVE SYSTEM NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Digestive System --- DIGESTIVE SYSTEM DISEASES
Liver --- DIGESTIVE SYSTEM DISEASES
Digestive System --- GASTROINTESTINAL DISEASES
Digestive System --- COLONIC DISEASES
Digestive System --- INTESTINAL DISEASES
MeSH Terms
COLORECTAL NEOPLASMS
INTESTINAL NEOPLASMS
GASTROINTESTINAL NEOPLASMS
DIGESTIVE SYSTEM NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
DIGESTIVE SYSTEM DISEASES
GASTROINTESTINAL DISEASES
COLONIC DISEASES
INTESTINAL DISEASES
RECTAL DISEASES
OXALIPLATIN
LEUCOVORIN
FLUOROURACIL
BEVACIZUMAB
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