This is a randomized, double-blind, phase III clinical trial. The study aims to demonstrate that the treatment regimen of Enlituo® plus FOLFOX is equivalent to that of Erbitux® plus FOLFOX in participants with RAS/BRAF wild-type and MSS/pMMR locally advanced/metastatic colorectal cancer. Enrolled participants will be stratified according to ECOG performance status (0 vs. 1) and primary tumor location (left-sided or right-sided colon) and randomly assigned in a 1:1 ratio to either the experimental group (Enlituo® + FOLFOX) or the control group (Erbitux® + FOLFOX). Participants will: * Receive Enlituo®/Erbitux®: 500 mg/m², administered via intravenous infusion over a minimum of 120 minutes, once every two weeks. * Receive FOLFOX * Participants in the Erbitux® plus FOLFOX group who achieve CR, PR, or SD at 16 weeks will cross over to receive Enlituo® plus FOLFOX. * Be recommended to undergo efficacy assessments every 8 weeks (±7 days). * Comply with the blood sample collection procedures for pharmacokinetic (PK) and immunogenicity analyses. * Be required to provide baseline tumor biopsy specimens or 8-10 unstained slides of archived tumor tissue (formalin-fixed, paraffin-embedded) from within the past 3 years. The Blinded Independent Central Review (BIRC) will assess: * Objective Response Rate (ORR) within 16 weeks. * Disease Control Rate (DCR) within 16 weeks. * Duration of Response (DoR). * Progression-Free Survival (PFS). The investigators will assess: * ORR within 16 weeks. * DCR within 16 weeks. * DoR. * PFS. * Overall Survival (OS). * Safety: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), as well as findings from laboratory tests, vital signs, and physical examinations. * Dose intensity, and incidence of dose interruptions, dose reductions, and treatment discontinuations due to AEs.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
608
Enlituo®: 500 mg/m², administered via intravenous infusion over a minimum of 120 minutes, once every two weeks. FOLFOX Regimen: Oxaliplatin: 85 mg/m², administered via intravenous infusion over 2 hours, on Day 1 of each treatment cycle. One treatment cycle spans 2 weeks. Leucovorin (LV): 400 mg/m², administered via intravenous infusion over 2 hours, on Day 1 of each treatment cycle. One treatment cycle spans 2 weeks. 5-Fluorouracil (5-FU): Bolus: 400 mg/m², administered via intravenous bolus, on Day 1 of each treatment cycle. Continuous Infusion: 1200 mg/(m²•day) for 2 days (total dose 2400 mg/m²), administered via continuous intravenous infusion over 46 to 48 hours, on Days 1 to 3 of each treatment cycle. One treatment cycle spans 2 weeks.
Erbitux®: 500 mg/m², administered via intravenous infusion over a minimum of 120 minutes, once every two weeks. Erbitux® will be administered for up to 16 weeks. Participants who continue to derive benefit (including SD, PR, and CR) after 16 weeks will crossover to receive Enlituo® combined with FOLFOX. FOLFOX Regimen: Oxaliplatin: 85 mg/m², administered via intravenous infusion over 2 hours, on Day 1 of each treatment cycle. One treatment cycle spans 2 weeks. Leucovorin (LV): 400 mg/m², administered via intravenous infusion over 2 hours, on Day 1 of each treatment cycle. One treatment cycle spans 2 weeks. 5-Fluorouracil (5-FU): Bolus: 400 mg/m², administered via intravenous bolus, on Day 1 of each treatment cycle. Continuous Infusion: 1200 mg/(m²•day) for 2 days (total dose 2400 mg/m²), administered via continuous intravenous infusion over 46 to 48 hours, on Days 1 to 3 of each treatment cycle. One treatment cycle spans 2 weeks.
Sun Yat-Sen University Cancer Center
Guangzhou, China
Objective Response Rate (ORR) within 16 weeks assessed by BIRC according to RECIST v1.1 criteria
The sum of the Complete Response (CR) rate and the Partial Response (PR) rate
Time frame: From enrollment to 16 weeks after the first dose.
Disease Control Rate (DCR) within 16 weeks assessed by BIRC according to RECIST v1.1 criteria
The proportion of patients whose tumor achieves a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) following treatment.
Time frame: From enrollment to 16 weeks after the first dose.
Duration of Response (DoR) assessed by the BIRC according to RECIST v1.1 criteria
The time from the date of the first documented complete or partial response (whichever is recorded first) until the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From the date of CR/PR to the date of the first documented progression or death from any cause, whichever occurs first, assessed up to at least 12 months of treatment for the last participant.
Progression-Free Survival (PFS) assessed by the BIRC according to RECIST v1.1 criteria
The time from randomization until objective tumor progression or death from any cause, whichever came first.
Time frame: From the date of randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to at least 12 months of treatment for the last participant.
Objective Response Rate (ORR) within 16 weeks assessed by the investigator according to RECIST v1.1 criteria
The sum of the Complete Response (CR) rate and the Partial Response (PR) rate
Time frame: From enrollment to 16 weeks after the first dose.
Duration of Response (DoR) assessed by the investigator according to RECIST v1.1 criteria
The time from the date of the first documented complete or partial response (whichever is recorded first) until the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From the date of CR/PR to the date of the first documented progression or death from any cause, whichever occurs first, assessed up to at least 12 months of treatment for the last participant.
Progression-Free Survival (PFS) assessed by the investigator according to RECIST v1.1 criteria
The time from randomization until objective tumor progression or death from any cause, whichever came first.
Time frame: From the date of randomization to the date of first documented progression or death from any cause, whichever came first, assessed up to at least 12 months of treatment for the last participant.
Overall Survival (OS)
The time from randomization to death from any cause.
Time frame: From the date of randomization until the date of death from any cause, assessed up to at least 12 months of treatment for the last participant.
Incidence and severity of adverse events (AEs)
Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), as well as findings from laboratory tests, vital signs, and physical examinations
Time frame: From the time the participant signs the informed consent form until 30 days after the last dose of study treatment.
Plasma concentration of Enlituo®/Erbitux®
Time frame: Cycle 1: Within 2 hours before the start of infusion, and within 15 minutes after the end of infusion. Cycle 2, 4, 8: Within 2 hours before the start of infusion (each cycle is 14 days). At the end of treatment, at least of 1 year.
Anti-drug antibody (ADA)
Time frame: Cycle 1, 2, 4, 8: Within 2 hours before the start of infusion (each cycle is 14 days). At the end of treatment, at least of 1 year.
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.