Phase III Study of Ivonescimab or Bevacizumab Combined With FOLFOX in Patients With Metastatic Colorectal Cancer (HARMONi-GI3)

Summit Therapeutics

Status and phase: Enrolling; Phase 3

Conditions: Metastatic Colorectal Cancer (CRC)

Treatments: Drug: Drug: Bevacizumab Injection; Drug: Drug: Ivonescimab Injection

Study type: Interventional

Funder types: Industry

Identifiers

NCT07228832

SMT112-3005

Details and patient eligibility

About

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)

Full 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.

Enrollment: 600 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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600 participants in 2 patient groups

Arm A: Ivonescimab in combination with mFOLFOX6

Experimental group

Description:

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.

Treatment:

Drug: Drug: Ivonescimab Injection

Arm B: Bevacizumab in combination with mFOLFOX6

Active Comparator group

Description:

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.

Treatment:

Drug: Drug: Bevacizumab Injection