OncoMatch/Clinical Trials/NCT06776757
Sintilimab in Combination with Cetuximab and Chemotherapy As First-line Treatment for RAS/BRAF Wild-type Advanced Colorectal Cancer
Is NCT06776757 recruiting? Yes, currently enrolling (May 2026). This Phase 1/2 trial studies multiple treatments including Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) and Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) for metastatic colorectal cancer.
Treatment: Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) · Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) — In 2018, global cancer incidence reached 18.1 million new cases, with 9.6 million cancer-related deaths. Colorectal cancer ranked as the third most common malignancy by incidence. Data from the U.S. NIH SEER database indicate a five-year survival rate for colorectal cancer of approximately 65%. Specifically, the survival rate is 90% for localized (non-metastatic) cases, 71% for regional (lymph node metastasis) cases, and only 14% for advanced metastatic cases. According to the China Society of Clinical Oncology (CSCO) guidelines, first-line therapy for advanced colorectal cancer typically involves chemotherapy combined with targeted agents, such as bevacizumab or cetuximab, yielding a median survival of 20-30 months. Prognosis is generally better for RAS wild-type patients compared to those with RAS mutations. In subsequent lines of therapy, chemotherapy combined with targeted therapy results in remission for approximately 22% of patients, although overall survival rarely exceeds 12 months. Basic research has demonstrated that cetuximab, when combined with chemotherapy, enhances the infiltration of NK cells, cytotoxic T cells, and other immune cells into the tumor microenvironment. In head and neck cancer, an increase in PD-1+ and TIM-3+ tumor-infiltrating lymphocytes (TILs) during cetuximab treatment was negatively correlated with treatment response. Blocking these immune checkpoints may improve cetuximab-based immunotherapy by reversing CD8+ TIL dysfunction, potentially enhancing clinical outcomes. The cetuximab-chemotherapy regimen increases tumor immunogenicity by inducing tumor cell death and antigen release. When combined with immune checkpoint inhibitors, cetuximab may convert "cold tumors" into "hot tumors," thus synergistically improving tumor cell elimination. Additionally, cetuximab has been shown to activate tumor-promoting M2 macrophages, particularly CD163-positive macrophages in colorectal cancer, which produce high levels of Fc-γ receptors and PD-L1, supporting the theoretical basis for combining cetuximab with immune checkpoint inhibitors in colorectal cancer treatment. In patients with locally advanced colorectal cancer, immune checkpoint inhibitors like PD-1 and CTLA-4 inhibitors have shown preliminary efficacy. The NICHE study reported a 100% pathological response in MSI-H patients and a 27% response in MSS-type patients, indicating potential benefits and safety of immunotherapy in both MSI-H sensitive and MSS/pMMR populations. For first-line treatment of advanced colorectal cancer, the BBCAPX Phase II study showed that sintilimab combined with CapeOX and bevacizumab resulted in an objective response rate (ORR) of 84% and a 100% disease control rate in RAS-mutant, MSS-type metastatic colorectal cancer (mCRC) patients. Similarly, the AIO-KRK-0216 study found that a combination of Avelumab (PD-L1), cetuximab, and chemotherapy produced an ORR of 79.5% in first-line MSS-type metastatic colorectal cancer. In later-line therapy, the REGONIVO Phase II study reported a 36% ORR for PD-1 monoclonal antibody combined with anti-angiogenesis agents (chemotherapy, targeted therapy) in metastatic colorectal cancer, with a 33% ORR for MSS-type patients. The median progression-free survival (PFS) was 7.9 months, though median overall survival (OS) had not been reached.
Check if I qualifyExtracted eligibility criteria
Cancer type
Colorectal Cancer
Biomarker criteria
Required: KRAS wild-type
Tumor tissue with both RAS and BRAF mutations being wild-type
Required: NRAS wild-type
Tumor tissue with both RAS and BRAF mutations being wild-type
Required: BRAF wild-type
Tumor tissue with both RAS and BRAF mutations being wild-type
Required: PD-L1 (CD274) CPS ≥1 or TPS ≥1% (CPS ≥1 or TPS ≥1%)
Tumor tissue with PD-L1 CPS ≥1, TPS ≥1%
Required: CD8 TILs ≥2% (TILs ≥2%)
Tumor tissue with CD8+ TILs ≥2%
Disease stage
Required: Stage IV
Metastatic disease required
Performance status
ECOG 0–1(Restricted strenuous activity)
Prior therapy
Cannot have received: chemotherapy
Exception: adjuvant therapy completed ≥ 6 months before enrollment
Previously received chemotherapy, cetuximab, or other anti-EGFR targeted therapies
Cannot have received: anti-EGFR targeted therapy (cetuximab)
Previously received chemotherapy, cetuximab, or other anti-EGFR targeted therapies
Cannot have received: anti-PD-L1 therapy
Previously received any of the following therapies: anti-PD-L1, anti-PD-L2 drugs, or drugs targeting other stimulatory or co-inhibitory T cell receptors (e.g., CTLA-4, OX-40, CD137)
Cannot have received: anti-PD-L2 therapy
Previously received any of the following therapies: anti-PD-L1, anti-PD-L2 drugs, or drugs targeting other stimulatory or co-inhibitory T cell receptors (e.g., CTLA-4, OX-40, CD137)
Cannot have received: checkpoint inhibitor
drugs targeting other stimulatory or co-inhibitory T cell receptors (e.g., CTLA-4, OX-40, CD137)
Lab requirements
Blood counts
ANC ≥ 1.5 x 10^9/L (no G-CSF in past 14 days); Platelet count ≥ 90 x 10^9/L (no transfusion in past 14 days); Hemoglobin > 9 g/dL (no transfusion or ESA in past 14 days)
Kidney function
Serum creatinine ≤ 1.5× ULN, and creatinine clearance (Cockcroft-Gault) ≥ 60 ml/min
Liver function
Total bilirubin ≤ 1.5× ULN; or total bilirubin > ULN but direct bilirubin ≤ ULN. AST, ALT ≤ 2.5× ULN (patients with liver metastasis are allowed to have ALT or AST ≤ ULN)
Cardiac function
Normal myocardial enzyme levels (subjects with isolated laboratory abnormalities that the investigator determines to have no clinical significance may still be eligible for inclusion). Significant and symptomatic abnormalities in rhythm, conduction, or morphology on resting ECG that are difficult to control, such as complete left bundle branch block, second-degree or higher heart block, ventricular arrhythmias, or atrial fibrillation; unstable angina, congestive heart failure, or chronic heart failure with NYHA classification ≥ 2.
Sufficient organ function and bone marrow compensation function are required, and the subjects must meet the following laboratory criteria: ... (see full criteria above)
Structured fields extracted by AI. May contain errors — verify against the official protocol.
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