Dual EGFR/HER2 Blockade Combined With Irinotecan for the Treatment of HER2-Positive Metastatic Colorectal Cancer
Summary
In colorectal cancer (CRC), HER2 has emerged as a critically targeted biomarker in recent years. Although multiple clinical trials have demonstrated the potential of HER2-targeted therapies in HER2-positive (overexpressed/amplified) metastatic CRC (mCRC), the duration of treatment response remains short with rapid disease progression. This underscores the urgent need to develop novel therapeutic strategies for HER2-positive mCRC. The EGFR pathway is constitutively activated in CRC and mediates resistance to HER2-targeted therapies through the formation of EGFR-HER2 heterodimers. Notably, EGFR-targeting antibodies combined with irinotecan can reverse irinotecan chemoresistance. Building upon these mechanisms, this study proposes to evaluate the combination of trastuzumab (anti-HER2), cetuximab beta (anti-EGFR), and irinotecan in chemotherapy-refractory HER2-positive mCRC.
Timeline
- Start
- 2025-07-11
- Primary completion
- 2027-12-30
- Completion
- 2028-12-30
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Cetuximab β | Monoclonal antibody | 500 mg/m2 | Intravenous |
| Subject | Irinotecan | Small molecule | 180 mg/m2 | Intravenous |
| Subject | Trastuzumab | Monoclonal antibody | 4 mg/kg | Intravenous |