Study of CMAB009 to Treat KRAS Wild Type Metastatic Colorectal Cancer

CMAB009 Plus Irinotecan Versus Irinotecan-only as Second-line Treatment After Fluoropyrimidine and Oxaliplatin Failure in KRAS Wild-type Metastatic Colorectal Cancer Patients: Prospective, Open-label, Randomized, Phase II/III Trial

The primary purpose of this study is to evaluate the clinical response and safety of CMAB009 plus irinotecan versus irinotecan-only as second-line treatment after fluoropyrimidine and oxaliplatin failure in KRAS wild-type metastatic colorectal cancer patients

CMAB009 is a recombinant, human/mouse chimeric monoclonal antibody (mAb) that binds specifically to the extracellular domain of EGFR. It is composed of the Fv regions of a murine anti-EGFR antibody with human IgG1 heavy and k light chain constant regions and it is expressed by Chinese hamster ovary cells. It has the same amino acid sequence as cetuximab (C225, Erbitux®) , but it has slightly different abilities for glycosylation and other post-translational modifications, and it is developed by Shanghai Zhangjiang Biotechnology Limited Company and produced by Biomabs. Phase I study results suggest that CMAB009 showed well-tolerated safety profile and primary efficacy. This multicenter, open-label study was to determine whether adding CMAB009 to irinotecan increased the response rate and prolongs survival in patients with KRAS wild-type metastatic colorectal cancer (mCRC) previously treated with fluoropyrimidine and oxaliplatin.

Inclusion Criteria:

• histologically confirmed metastatic colorectal adenocarcinoma
• KRAS wild-type tumors, EGFR-expressing or EGFR-nonexpressing by immunohistochemistry;
• has measurable lesion, at least 1cm in diametre by CT or MRI, at least 2cm diametre by physical examination or other iconography
• ECOG performance status 0 to 1
• Failure (disease progression/discontinuation due to toxicity) of fluoropyrimidine and oxaliplatin treatment,stop at least one month thereafter, irinotecan-naïve

Exclusion Criteria:

• Previous irinotecan or anti-EGFR therapies
• hematologic function: hemoglobin, less than 90g per liter; neutrophil count, less than 1500 per cubic millimeter; and platelet count, less than 100,000 per cubic millimeter
• liver function: bilirubin, more than 1.0 times the upper limit of normal; aspartate aminotransferase and alanine aminotransferase, more than 5.0 times and 2.5 times the upper limit of normal with hepatic metastasis or not
• Renal function: serum creatinine, more than 1.5 times the upper limit of normal
• Patients with symptomatic central nervous system metastases