Metastatic Colorectal Cancer (CRC)
Conditions
Brief summary
This is a prospective randomized controlled Phase Ⅱ/Ⅲ Clinical study to evaluate the clinical efficacy and safety of Envafolimab combining with Cetuximab -β and mFOLFOX6 in Patients With MSS, RAS/BRAF Wild-Type Metastatic Colorectal Cancer (mCRC)
Detailed description
Patients diagnosed with unresectable, microsatellite - stable (MSS), RAS/BRAF wild - type metastatic colorectal adenocarcinoma who have not received prior systemic anti-neoplastic therapy for metastatic or recurrent lesions will be included in this study. In the Phase II study, approximately 186 patients will be enrolled, with 93 assigned to the experimental group and 93 to the control group. In the Phase III study, around 404 patients will be recruited, with 202 allocated to the experimental group and 202 to the control group. Eligible patients will undergo a screening period of up to 28 days, followed by a treatment period consisting of 2 - week cycles for a maximum duration of 2 years. Subsequently, a follow - up period will be implemented, which includes a safety follow - up and survival follow - ups conducted every 12 weeks.
Interventions
DRUGCetuxima-β
500 mg/m², initial intravenous infusion (IV)\>120 min, subsequent IV \>60 min , D1，every 2 weeks
DRUGEnvafolimab
a single fixed dose of 200 mg, subcutaneous injection(SC), every 2 weeks (Day 1 of each cycle \[D1\])
DRUGmFOLFOX6
Oxaliplatin 85 mg/m² , IV, over 120 min, Day 1; Leucovorin 400 mg/m² (or Calcium Folinate 200 mg/m²), IV, over 120 min, D1; 5-FU 400 mg/m² , bolus injection, followed by 1200 mg/(m²·d) continuous IV for 2 days (total dose 2400 mg/m² over 46 - 48 hours)
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Experimental Arm: Cetuximab β + mFOLFOX6 + Envafolimab • Induction Phase (12 cycles): o Patients receive cetuximab β + mFOLFOX6 + envafolimab. o Patients who achieve CR/PR/SD (no disease progression) after 12 cycles proceed to the maintenance phase. • Maintenance Phase: o Cetuximab β + 5-FU + envafolimab Control Arm: Cetuximab β + mFOLFOX6 • Induction Phase (12 cycles): o Patients receive cetuximab β + mFOLFOX6. o Patients who achieve CR/PR/SD (no disease progression) after 12 cycles proceed to the maintenance phase. • Maintenance Phase: o Cetuximab β + 5-FU
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients are eligible for the study if they meet all of the following criteria: 1. Prior to enrollment, the participant is required to sign a written informed consent form. 2. Participants should be above 18 years，regardless of gender. 3. Histopathologically confirmed untreated advanced colorectal adenocarcinoma. 4. Tumors with RAS (KRAS, NRAS, HRAS) and BRAF wild-type, MSS phenotype, excluding appendiceal or anal cancer. All listed codons must be wild-type: KRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146) ; NRAS: Exons 2, 3, 4 (Codons 12, 13, 59, 61, 117, 146) 5. Imaging (enhanced CT/MRI/PET-CT) confirms advanced/metastatic colorectal cancer with measurable lesions according to RECIST v1.1. 6. No prior systemic therapy for advanced/metastatic colorectal cancer, including chemotherapy, EGFR inhibitors (cetuximab, panitumumab), VEGF inhibitors (bevacizumab), and immune checkpoint inhibitors (anti-PD-1/PD-L1/CTLA-4). Adjuvant/neoadjuvant chemotherapy within 6 months before recurrence/metastasis is considered first-line therapy. 7. ECOG PS score 0-1. 8. Expected survival \>12 weeks. 9. Adequate organ function (without blood component or growth factor use within 14 days): Hematology:Neutrophils ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L. Liver/kidney function: SCr ≤1.5×ULN or creatinine clearance ≥50 ml/min, TBIL ≤1.5×ULN, AST/ALT ≤2.5×ULN (≤5×ULN if due to liver metastasis), urine protein \<2+ (≤1g/24h if ≥2+). 10. Normal coagulation, no active bleeding/thrombosis: INR ≤1.5×ULN, APTT ≤1.5×ULN, PT ≤1.5×ULN. 11. Non-surgically sterile women of childbearing potential must use contraception during and 3 months after treatment; serum/urine HCG negative within 7 days before enrollment; not breastfeeding. Non-surgically sterile men must use contraception with partners during and 3 months after treatment. 12. Willing participant with good compliance for safety and survival follow-up.
Exclusion criteria
\- * Patients will be excluded from the study if they meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progressin Free Survival，PFS | Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 3 years | Progression-free survival based on RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| OS，Overall survival | from the date of first dose unitl the date of death from any cause，assessed up to 3 years | — |
| ORR， Objective response | up to 3 years | Objective response rate based on RECIST v1.1 |
| DCR， Disease control rate | up to 1 year | the proportion of patients with the best overall response of CR, PR, or stable disease (SD) |
| NED Rate， No Evidence of Disease Rate | up to 3 years | The proportion of participants with no evidence of disease after treatment, as determined by current assessments (pathological, imaging, and molecular biology). NED includes complete response (CR), R0 resection, or other local treatments, such as radiofrequency, microwave, or cryoablation (which can be combined with surgery), that eliminate the tumor. |
| Safety(Adverse Event (AE) Incidence) | up to 3 years | Adverse Event (AE) Incidence |
Countries
China
Contacts
Primary ContactRuihua Xu, PhD
Outcome results
None listed