NCT06776757

Sintilimab in Combination with Cetuximab and Chemotherapy As First-line Treatment for RAS/BRAF Wild-type Advanced Colorectal Cancer

Recruiting now Phase 1, PHASE2 Last updated 15 January 2025

What this trial tests

Phase 1, PHASE2 trial testing Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) in Metastatic Colorectal Cancer in 30 participants. Currently enrolling.

Timeline

25 December 2023

Primary endpoint
25 June 2025

25 December 2025

Quick facts

Lead sponsor	Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center
Phase	Phase 1, PHASE2
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	non randomized
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	30
Start date	25 December 2023
Primary completion	25 June 2025
Estimated completion	25 December 2025
Sites	1 location across China

Drugs / interventions tested

• Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) — full drug profile →
• Sintilimab+Cetuximab+Chemotherapy (mFOLFOX6/FOLFIRI/CAPEOX/CAPIRI) — full drug profile →

Conditions studied

• Metastatic Colorectal Cancer — all drugs for Metastatic Colorectal Cancer →

Sponsor

Cancer Hospital Chinese Academy of Medical Science, Shenzhen Center

Who can join

Adults 18 to 75, any sex, with Metastatic Colorectal Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

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.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. BRAF Targeting Across Solid Tumors: Molecular Aspects and Clinical Applications.
   Mechahougui H, Gutmans J, Gouasmi R, Smekens L, et al · · 2025 · cited 7× · PMID 40332392 · DOI 10.3390/ijms26083757
2. Combination immunotherapy for colorectal cancer: Clinical applications, rationale, challenges, and future perspectives.
   Fei J, Cai C, Wu W, Shen H, et al · · 2026 · PMID 41950929 · DOI 10.1016/j.xcrm.2026.102728