Metastatic Colorectal Cancer (CRC)
Conditions
Keywords
mCRC, Ivonescimab
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)
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.
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.
Sponsors
Summit Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PFS by IRRC based on RECIST v1.1 | Up to approximately 2.5 years | Progression-free survival (PFS) assessed by IRRC per RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in the population | Up to approximately 4 years | Overall Survival (OS) in the mCRC population |
| ORR | Up to approximately 2.5 years | 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 |
| Adverse Events (AE) | Up to approximately 4 years | incidence and severity of adverse events (AEs) and clinically significant abnormal laboratory test results \[From the time subject signs the ICF to 30 days (AE) and 90 days (SAE related to ivonescimab/bevacizumab) after the last dose of study treatment or initiation of other anticancer therapy, whichever occurs first\] |
| DoR | up to approximately 2.5 years | 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 |
Countries
Belgium, Canada, China, Czechia, France, Germany, Hungary, Italy, Japan, Poland, Puerto Rico, Spain, United Kingdom, United States
Contacts
CONTACTNing Chang, MD
Outcome results
None listed