A Preliminary Clinical Study on the Pharmacokinetics and Safety of CDP1 in Patients With Advanced CRC or HNSCC

OBJECTIVES:

Primary:

To compare the pharmacokinetic characteristics of a single dose between CDP1 and the original drug Erbitux In patients with advanced metastatic colorectal cancer.

Secondary :

• To compare the safety and immunogenic characteristics of the single dose between CDP1 and the original drug Erbitux in patients with advanced metastatic colorectal cancer.
• To evaluate the pharmacokinetics and safety of CDP1 multiple administrations."

OUTLINE

The study can be divided into 3 parts:

Part 1: Single-dose Phase:

single center, parallel, randomized, single-blind trial. The original drug Erbitux as a control, CDP1 and Erbitux single-dose pharmacokinetics of the initial comparison, and at the same time safety and immunogen preliminary comparison. CDP1 group received a single administration of CDP1 250mg/m2, Erbitux group received Erbitux 250mg/m2 single administration. Two groups of subjects after a single administration into the 4-week observation period, safety observations, pharmacokinetic blood samples and immunogenic blood samples were collected. The tumor was evaluated at the end of the 4 week observation period.If the subjects did not develop the disease, or did not appear the intolerant toxicity during the observation period, they entered the period of multiple drug delivery.

Part 2: Multi-dose Phase:

Single center, single arm, open trial, evaluation of pharmacokinetics and safety with multiple doses of CDP1. Multiple administrations of two groups of subjects were followed by continuous administration of CDP1. Dosing regimen is the first administration of 400mg/m2, followed by 250mg/m2, once a week for 6 weeks.

Part 3: Follow-up Phase:

CDP1, IV, once a week, 250mg/m2, until the patient's death or the withdrawal decision of the patient and/or investigator.

Inclusion criteria

• Age 18 ~ 75 (inclusive) years , male.
• Histologically or cytologically confirmed ras genotype is wild-type patients with advanced metastatic colorectal cancer, at least second-line chemotherapy (including oxaliplatin, irinotecan and fluorouracil drugs) failed, or intolerant to Irinotecan or chemotherapy-denied patients.
• ECOG physical score 0-2 points.
• Expected survival time of 3 months or more.
• According to RECIST 1.1, there is at least one assessable tumor lesion.
• No serious hematological system, liver function, renal function and coagulation dysfunction:Neutrophils ≥1.5 × 109 / L, platelets ≥75 × 109 / L, hemoglobin≥90g / L; total bilirubin≤1.5 times ULN, alanine aminotransferase (ALT)≤2.5 times ULN,aspartate transaminase (AST) ≤2.5 times ULN (liver metastasis ALT ≤ 5 times ULN, AST≤ 5 times ULN);Serum creatinine ≤1.5 times ULN;Activated partial thromboplastin time (APTT) ≤1.5 times ULN, prothrombin time (PT) ≤1.5 times ULN, international normalized ratio (INR) ≤1.5 times ULN.
• Eligible patients with fertility must agree to use reliable methods of contraception (hormonal or barrier abstinence) for at least 12 weeks during and after the last dose of medication.
• Subjects should be informed of the study prior to the test and voluntarily sign a written informed consent form.

Exclusion criteria

• Chemotherapy, biotherapy, radiation therapy, endocrine therapy, small molecule targeted therapies and other anti-tumor, etc. within 4 weeks prior to the start of study drug use or within 5 half-lives of the known drug (whichever is longer) Anti-cancer therapy, or other experimental drug treatment (except nitrosourea, mitomycin C and fluorouracil oral drugs),nitrosourea or mitomycin C for 6 weeks. Fluorouracil-based oral medications, such as tiotropium and capecitabine, have an interval of at least 2 weeks between the last oral dose and study drug use.
• Have previously received anti-EGFR monoclonal antibody treatment.
• EGFR antibody drug-resistant antibody (ADA) positive.
• Within 3 months prior to enrollment, major organ surgery (excluding biopsy) or significant trauma occurred.
• The adverse reactions of previous anti-tumor therapy have not been restored to CTCAE 4.03 grade ≤1 (excluding hair loss).
• Untreated or clinically symptomatic brain metastases, spinal cord compression, cancerous meningitis, or other evidence that the patient's brain, spinal metastases have not yet been controlled, the researchers judged not suitable for inclusion. clinical symptoms suspected brain or soft Membrane disease is to be ruled out by CT / MRI examination.
• Uncontrolled active infections.
• Have a history of immunodeficiency, including HIV antibody test positive.
• Treponema anti-positive.
• Chronic hepatitis B virus (HBV) infection; Hepatitis C virus (HCV) infection.
• Serious history of cardiovascular disease: including ventricular arrhythmias requiring clinical intervention; acute coronary syndromes, congestive heart failure, stroke or other cardiovascular events of grade III and higher within 6 months; New York, USA Heart Association (NYHA. Cardiac function grade ≥II or Left ventricular ejection fraction(LVEF) <50%; poorly controlled hypertension (systolic blood pressure> 150 mmHg, diastolic blood pressure> 90 mmHg).
• Interstitial lung disease.
• There are other serious history of systemic diseases, the researchers judged not suitable for clinical trials of patients.
• Alcohol or drug dependence is known.
• Persons with mental disorders or poor compliance.
• Moderate or severe infusion-related reactions, including anaphylaxis, have been reported in the past when using monoclonal antibody drugs.
• The investigators did not find it appropriate to participate in this clinical study because of any clinical or laboratory abnormalities or other causes.