A Study of Recombinant Anti-EGFR Monoclonal Antibody in Patients With Metastatic Colorectal Cancer

This is an open-label, parallel designed study to assess the pharmacokinetics, safety and tolerability of the single-dose and multi-dose of a recombinant anti-EGFR monoclonal antibody (CPGJ602) in patients with at least one prior chemical regimen failed metastatic colorectal cancer. The immunogenicity and preliminary efficacy of CPGJ602 will also be assessed. The study includes 3 parts: part 1: after a single dose of CPGJ602 or cetuximab (the active comparator), the patients will be observed for 4 weeks; part 2: CPGJ602 or cetuximab will be administered to the patients once a week for 5 weeks; part 3: CPGJ602 will be administered to the patients once a week until the patient's death or the withdrawal decision of the patient and/or investigator.

OBJECTIVES:

Primary:

To assess the pharmacokinetics, safety and tolerability of the single-dose and multi-dose of CPGJ602 administered by intravenous infusion.

Secondary:

To assess the immunogenicity and anti-tumor activity of CPGJ602, compare the pharmacokinetics and immunogenicity between CPGJ602 and the active comparator, cetuximab, and to provide scientific basis for the subsequent phase 2/3 clinical trials.

OUTLINE:

This is an open-label, parallel designed study in patients with at least one prior chemical regimen failed metastatic colorectal cancer. The study can be divided into 3 parts:

Part 1: Single-dose Part

* Arm A: CPGJ602, IV over 2 hours, 100 mg/m2 X 1;
* Arm B: CPGJ602, IV over 2 hours, 400 mg/m2 X 1;
* Arm C: Cetuximab, IV over 2 hours, 400 mg/m2 X 1.

Part 2: Multi-dose Part

The subjects from arm A in Part 1 will be randomized into arm B or C.

* Arm B: CPGJ602, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time;
* Arm C: Cetuximab, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time. The completion of Day 63 Visit (the visit on the 7th day after the 5th dose in Part 2) can be considered as the completion of the study.

Part 3 (Follow-up Part)

CPGJ602, IV over 1 hour, QW, 250mg/m2, until the patient's death or the withdrawal decision of the patient and/or investigator.

Eligibility Criteria:
Inclusion Criteria:

1. 18-70 years old, male or female.
2. Histologically or cytologically confirmed metastatic CRC, and have failed (disease progression or intolerance) at least one prior chemical regimen containing oxaliplatin, irinotecan or 5-FU, etc.
3. ECOG performance status 0 or 1.
4. Estimated life expectancy ≥ 3 months.
5. RAS (including K-ras and N-ras) wide type status.
6. Adequate bone marrow, hepatic and renal functions. Hematopoietic:

   Leukocytes (WBC)\>4.0×109/L or Absolute Neutrophil Count (ANC)\> 1.5×109/L, Platelet Count (PLT)\>80×109/L, Hemoglobin (Hb)\>90g/ L; Hepatic: Total Bilirubin (T-Bil)≤1.5×ULT (Upper Limit of Normal), Alanine Transaminase (ALT)/ Aspartate Transaminase (AST)≤2.5×ULT or ≤5×ULT in case of liver metastases; Renal: Blood Urea Nitrogen (BUN)≤1.5×ULT, Serum Creatinine (Cr) ≤ 1.5×ULT.
7. At least one measurable disease based on RECIST criteria (v 1.1).
8. Signed informed consent on a voluntary basis at screening, and no geographical condition that would preclude the study compliance.

Exclusion Criteria:

1. Less than 28 days since prior chemotherapy, radiotherapy or surgery (diagnosis biopsy is allowed).
2. Previous epidermal growth factor receptor (EGFR) targeted therapies (including monoclonal antibody, tyrosine kinase inhibitor \[TKI\] and other EGFR targeted therapies, such as cetuximab, nimotuzumab, panitumumab, gefitinib, erlotinib, and icotinib, etc.
3. Known hypersensitivity to study drugs or any of the excipients.
4. Known or clinical suspected brain metastases and/or disease of meninges.
5. Clinically significant cardiovascular or cerebrovascular dis ease, history of myocardial infarction (MI) in the latest 6 months, or high-risk of uncontrolled cardiac arrhythmias.
6. History of acute or sub-acute intestinal obstruction, or of inflammatory bowel disease.
7. A serious and uncontrolled concomitant disease which, in the investigator's opinion, rules out the patient's participation in the study, such as history of malignancies other than CRC (with the exception of: curatively treated carcinoma of the skin \[except for melanoma\]; cured cervical cancer or basal cell skin cancer, ductal carcinoma in situ \[DICS\], endometrial carcinoma \[stage I grade 1\]; and other solid tumors including lymphoma without bone marrow infiltration for which the patient has been disease-free for 5 years), uncontrolled hypertension, diabetes mellitus (DM), peripheral neuropathy, and infectious diseases (including viral, bacterial and parasitic infections), etc.
8. Pregnancy or lactation, or a fertility plan during the participation in this study.
9. No more than 4 weeks or no more than 5 times of t1/2 since prior investigational agents.
10. Other situations that impede the patient's participation in the study at the discretion of the investigator.