Thsi study is a randomised, parallel-controlled phase II/III trial evaluating FOLFIRI plus bevacizumab with or without QL1706 as second-line therapy for metastatic colorectal cancer. The primary endpoint is PFS. Secondary endpoint includes overall survival, objective response rate, safety profiles, immune-related adverse events, and patient quality of life. Exploratory analyses focus on dynamic shifts in tumour immune microenvironment and biomarkers, aiming to identify predictive signatures for therapeutic efficacy and immune toxicities.
This is a prospective, randomised, parallel-controlled phase II/III clinical trial designed to investigate the efficacy and safety of adding QL1706, a dual PD-1/CTLA-4 bispecific immune checkpoint inhibitor, to the standard second-line FOLFIRI plus bevacizumab regimen in patients with metastatic colorectal cancer. Eligible participants who have progressed after first-line oxaliplatin-based systemic therapy will be randomly assigned to either the experimental group receiving combination treatment with FOLFIRI, bevacizumab and QL1706 or the control group treating with FOLFIRI plus bevacizumab alone, to conduct head-to-head comparative analysis of clinical outcomes. The primary endpoint of the trial is progression-free survival. Secondary endpoints comprehensively evaluating overall survival, objective response rate, disease control rate, the incidence and severity of treatment-related adverse events and immune-related adverse events. Exploratory analyses are pre-specified in this trial. Serial detection and dynamic analysis of tumour immune microenvironment characteristics and multiple peripheral biomarkers will be performed to clarify the immunomodulatory effect of the triple combination regimen. Furthermore, correlative analyses will be conducted to screen and validate potential predictive signatures, including immune cell subsets, cytokine profiles and molecular biomarkers, for clinical treatment response and immune-related toxicities, aiming to provide precise evidence for individualised second-line immunotherapy combined with targeted chemotherapy for metastatic colorectal cancer.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
270
QL1706 (4mg/kg on day 1), Bevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by QL1706 plus bevacizumab and fluoropyrimidine based maintence treatment.
Bevacizumab (5 mg/kg on day 1) plus mFOLFIRI ( irinotecan 180 mg/m2, and folinic acid 400 mg/m2 followed by bolus 5-fluorouracil 400 mg/m2 and 5-fluorouracil 2400mg/m2 as a 46-hour continuous infusion on day 1) for 8 cycles and followed by bevacizumab and fluoropyrimidine based maintence treatment.
The sixth affiliated hospital of Sun Yat-sen University
Guangzhou, Guangdong, China
Progression-free survival (PFS)
The PFS is defined as the time from the start of treatment to the date of first documented PD or death as a result of any cause, whichever occurred first.
Time frame: 2 years
Objective response rate (ORR)
The percentage of subjects with total number of Complete Response (CR) + total number of Partial Response (PR)
Time frame: 2 years
Overall Survival (OS)
OS is defined as the time from date of randomization to death due to any cause. Subjects still alive at the time of analysis were censored at their last date of last contact.
Time frame: 5 years
Toxicity assessed using the NCI common toxicity criteria, version 5.0.
The grade of toxicity will be assessed using the NCI common toxicity criteria, version 5.0.
Time frame: 2 years
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