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

Phase 1

• Conditions: Metastatic Colorectal Cancer
• Interventions: Biological: CPGJ602; Biological: Cetuximab

• Registration Number: NCT03356158
• Lead Sponsor: Sunshine Guojian Pharmaceutical (Shanghai) Co., Ltd.

Brief Summary

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.

Detailed Description

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.

Study Timeline

• Status Verified: 2017-11
• Study First Submitted: 2017-11-09
• Study Start: 2017-11-15
• Study First Submitted QC: 2017-11-22
• Study First Posted: 2017-11-29
• Last Update Submitted: 2018-09-13
• Last Update Posted: 2018-09-17
• Primary Completion: 2018-10-30
• Study Completion: 2018-11-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 21

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
CPGJ 602 normal dose	CPGJ602	Part 1: CPGJ602, IV over 2 hours, 400 mg/m2 X 1; Part 2: CPGJ602, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time;
CPGJ 602 low dose	CPGJ602	Part 1: CPGJ602, IV over 2 hours, 100 mg/m2 X 1;
Cetuximab normal dose	Cetuximab	Part 1: Cetuximab, IV over 2 hours, 400 mg/m2 X 1. Part 2: Cetuximab, IV, QW, 400 mg/m2 X 1, over 2 hours, followed by 250mg/m2 X4, over 1 hour for each time.

Primary Outcome Measures

Name	Time	Method
Incidence of Adverse Events [AEs]	Day -28 to 1 month following the last administration	to evaluate the safety and tolerability
Maximum Plasma Concentration [Cmax]	Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses	part 1 for single dose and part 2 for multiple doses
Half life of CPGJ602 in blood [t1/2]	Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses	part 1 for single dose and part 2 for multiple doses
Area Under the Curve [AUC]	Day 0 - Day 21 for single dose and Day 28 - Day 63 for multiple doses	part 1 for single dose and part 2 for multiple doses

Secondary Outcome Measures

Name	Time	Method
Anti-Drug Antibody [ADA]	Day 0 to Day 63, and in the follow-up period.	to evaluate the Immunogenicity; if the result is positive, Neutralizing Antibody \[NAB\] will also be assessed.
Cancer antigen [CA19-9]	Day -28 - Day 63	Tumor Marker
Objective Response Rate [ORR]	Day -28 - Day 63	the rate of completely response \[CR\] and partial response \[PR\] patients
Carcinoembryonic antigen [CEA]	Day -28 - Day 63	Tumor Marker

Trial Locations

Locations (1)

Sir Run Run Shaw Hospital; 🇨🇳 Hangzhou, Zhejiang, China