Colorectal Cancer
Conditions
Brief summary
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.
Interventions
BIOLOGICALEnlituo®
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.
BIOLOGICALErbitux®
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.
Sponsors
Taizhou Mabtech Pharmaceutical Co.,Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Voluntarily participate in the study and sign the informed consent form. * Aged 18 years or older. * Participants with histologically and/or cytologically confirmed locally advanced/metastatic colorectal cancer. * Have at least one evaluable or measurable tumor target lesion (RECIST v1.1). Lesions that have received previous local therapy or locoregional therapy (e.g., radiotherapy, hepatic arterial embolization, radiofrequency ablation, and percutaneous intervention) should not be considered measurable lesions unless progression is observed after the local or locoregional therapy. * Have not received prior systemic anti-tumor therapy for locally advanced/metastatic colorectal cancer. Previous neoadjuvant or adjuvant therapy for colorectal cancer is allowed if completed ≥6 months before the detection of disease recurrence or metastasis. * Have an ECOG performance status of 0 or 1. * Have a life expectancy of ≥12 weeks. * Have locally advanced/metastatic colorectal cancer confirmed by a local laboratory to be RAS/BRAF wild-type and MSS/pMMR. Note: RAS wild-type refers to wild-type status for KRAS exons 2, 3, 4 and NRAS exons 2, 3, 4. -Have adequate organ and bone marrow function (no administration of hematopoietic growth factors, blood transfusion, or platelets within 2 weeks prior to the first dose of study treatment). Hematology: Absolute Neutrophil Count (ANC) ≥1.5 × 10⁹/L Platelets ≥100 × 10⁹/L Hemoglobin ≥90 g/L Liver Function : ALT and AST in participants without liver metastases ≤2.5 × Upper Limit of Normal (ULN) Serum Total Bilirubin in participants without liver metastases ≤1.5 × ULN ALT and AST in participants with liver metastases ≤5 × ULN Serum Total Bilirubin in participants with liver metastases or Gilbert's syndrome ≤3 × ULN Renal Function : Creatinine Clearance calculated by Cockcroft-Gault formula ≥50.0 mL/min Coagulation International Normalized Ratio (INR) or Activated Partial Thromboplastin Time (aPTT) INR ≤1.5 or aPTT ≤1.5 × ULN (For participants receiving anticoagulant therapy, the investigator must judge the INR and/or aPTT to be within a safe and effective therapeutic range.) Cardiac Function: Left Ventricular Ejection Fraction (LVEF) measured by echocardiography or Multiple Gated Acquisition (MUGA) scan \>50% * Women of childbearing potential (WOCBP) must agree to use reliable contraceptive methods to avoid the risk of pregnancy throughout the study treatment period and for 180 days after the last dose of study treatment. * WOCBP must have a negative serum pregnancy test result within 72 hours before the first dose of the investigational product. * Female participants must not be breastfeeding. * Male participants must agree to use reliable contraceptive methods from the first dose of study treatment until 180 days after the last dose of study treatment.
Exclusion criteria
* History of other active malignancies within the past 3 years, except for locally curable tumors deemed by the investigator to have a low risk of recurrence (e.g., basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast) * Has not recovered from adverse events (AEs) due to prior anti-tumor therapy (i.e., not recovered to ≤ Grade 1 or to baseline, with the exception of alopecia, hypothyroidism controllable with hormone replacement therapy, and well-controlled type 1 diabetes on insulin therapy). * Prior treatment with EGFR-targeted antibodies (e.g., cetuximab, panitumumab, etc.), antibody-drug conjugates (ADCs) (e.g., MRG003, SHR-A1307, RC-68, etc.), or signal transduction inhibitors (e.g., gefitinib, osimertinib, etc.). * Currently participating in and receiving investigational drug therapy from another clinical trial, or has received investigational drug therapy or used an investigational device within 4 weeks prior to the first dose of study treatment (Note: this does not include the follow-up period of a study). * Major surgery within 4 weeks prior to the first dose of study treatment, or open biopsy within 1 week prior. (Minor procedures such as mediastinoscopy, placement of a central venous access device, placement of a gastric tube, needle biopsy, and percutaneous nephrostomy are not considered major surgery). * Any chemotherapy, immunotherapy, experimental therapy, or other anti-tumor therapy within 28 days or 5 half-lives (whichever is shorter, but at least 14 days) prior to the first dose of study treatment. Treatment with anti-tumor traditional Chinese medicine preparations or any radiotherapy within 2 weeks prior to the first dose of study treatment. * Known central nervous system metastases and/or carcinomatous meningitis. Ascites, pleural effusion, or pericardial effusion requiring drainage or medical intervention within 4 weeks prior to the first dose of study treatment. * Known active infection requiring systemic therapy administered intravenously within 2 weeks prior to the first dose of study treatment. * History of active tuberculosis infection within 1 year. (Participants with a history of active tuberculosis may be eligible if the investigator judges there is no evidence of active tuberculosis for more than 1 year prior to the first dose of study treatment). * History of non-infectious pneumonitis requiring oral or intravenous steroids to aid recovery, or history of pulmonary fibrosis, interstitial lung disease, radiation pneumonitis, drug-related pneumonitis, or other severe lung function impairment such as severe chronic obstructive pulmonary disease. * Acute or subacute intestinal obstruction, or inflammatory bowel disease. Concomitant Diseases/Other
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) within 16 weeks assessed by BIRC according to RECIST v1.1 criteria | From enrollment to 16 weeks after the first dose. | The sum of the Complete Response (CR) rate and the Partial Response (PR) rate |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease Control Rate (DCR) within 16 weeks assessed by BIRC according to RECIST v1.1 criteria | From enrollment to 16 weeks after the first dose. | The proportion of patients whose tumor achieves a Complete Response (CR), Partial Response (PR), or Stable Disease (SD) following treatment. |
| Duration of Response (DoR) assessed by the BIRC according to RECIST v1.1 criteria | 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. | 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. |
| Progression-Free Survival (PFS) assessed by the BIRC according to RECIST v1.1 criteria | 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. | The time from randomization until objective tumor progression or death from any cause, whichever came first. |
| Objective Response Rate (ORR) within 16 weeks assessed by the investigator according to RECIST v1.1 criteria | From enrollment to 16 weeks after the first dose. | The sum of the Complete Response (CR) rate and the Partial Response (PR) rate |
| Duration of Response (DoR) assessed by the investigator according to RECIST v1.1 criteria | 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. | 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. |
| Progression-Free Survival (PFS) assessed by the investigator according to RECIST v1.1 criteria | 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. | The time from randomization until objective tumor progression or death from any cause, whichever came first. |
| Overall Survival (OS) | 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. | The time from randomization to death from any cause. |
| Incidence and severity of adverse events (AEs) | From the time the participant signs the informed consent form until 30 days after the last dose of study treatment. | Incidence and severity of adverse events (AEs) and serious adverse events (SAEs), as well as findings from laboratory tests, vital signs, and physical examinations |
| Plasma concentration of Enlituo®/Erbitux® | 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) | 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. | — |
Countries
China
Contacts
CONTACTJiang Guo
Outcome results
None listed