Phase I Clinical Trial of CDP1 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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The main purpose of this study was to evaluate the safety and tolerability of CDP1 in patients with advanced solid tumor, to explore dose limited toxicity (DLT), and to determine the recommended dose (RP2D) for phase II clinical trials.

Detailed Description
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OBJECTIVES: Primary: To evaluate the safety and tolerability of CDP1 in patients with advanced solid tumor, to explore the dose limited toxicity (DLT), and to determine the recommended dose (RP2D) for phase II clinical trial. Secondary: To evaluate the pharmacokinetics of CDP1 in patients with advanced solid tumor. To evaluate the immunogenicity of CDP1 in patients with advanced solid tumor. To evaluate the initial efficacy of CDP1 in patients with advanced solid tumor.

Official Title
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Phase I Clinical Trial to Evaluate Safety, Tolerance and Pharmacokinetics of Recombinant Anti-EGFR Human Mouse Chimeric Monoclonal Antibody Injection (CDP1) in Patients With Advanced Solid Tumors

Conditions
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Advanced Tumors

Intervention / Treatment
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* Drug: CDP1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age: 18-75 (inclusive), gender unlimited; Patients with advanced solid tumors confirmed by histology or cytology who have failed to receive the existing standard treatment or are unable to tolerate or unwilling to accept the standard treatment (tumor types benefiting from anti EGFR treatment, including but not limited to colorectal cancer, head and neck squamous cell carcinoma, esophageal squamous cell carcinoma, penile squamous cell carcinoma, etc.); For colorectal cancer patients, RAS / BRAF was detected as wild-type. ECOG physical strength score: 0-1; Expected survival time over 3 months; According to RECIST1.1, there is at least one tumor lesion that can be assessed; No serious abnormalities of blood system, liver function, renal function and coagulation function: Neutrophils ≥1.5×10 9 /L, platelets ≥ 75 × 10 g/L, hemoglobin ≥ 90g/L;Total bilirubin ≤ 1.5ULN, ALT ≤ 2.5ULN, AST ≤ 2.5ULN (ALT ≤ 5ULN, AST ≤ 5ULN in patients with liver metastasis); Blood creatinine ≤ 1.5ULN; APTT ≤ 1.5ULN, Pt ≤ 1.5ULN, INR ≤ 1.5ULN; Eligible fertile patients (male and female) must agree to use a reliable method of contraception (hormonal or barrier or abstinence) during the trial and for at least 12 weeks after the last dose; Women of childbearing age must have a negative blood or urine pregnancy test within 7 days of enrollment; Subjects shall give informed consent to the study before the trial and sign written informed consent voluntarily; Exclusion Criteria: Received chemotherapy, biotherapy, radiotherapy, endocrinotherapy, small molecule targeted therapy and other anti-tumor treatment (except for nitrosourea, mitomycin C and fluorouracil oral drugs) within 4 weeks before starting to use the study drug or within 5 half-lives of the known drug (whichever is longer) .6 weeks for nitrosourea or mitomycin C; The interval between the last oral administration of fluorouracil, such as tegio and capecitabine, and the use of the study drug is at least 2 weeks. Received other clinical trials within 4 weeks before enrollment, or within 5 half lives of known drugs, whichever is the longer elution / withdrawal time; Have received EGFR inhibitor treatment before; Patients who had undergone major organ surgery (excluding puncture biopsy) or had significant trauma but not recovered within 4 weeks before admission; The adverse reactions of the previous anti-tumor treatment have not been restored to CTCAE 5.0 grade evaluation ≤ 1 (except for hair loss); the radiotoxicity has not been restored to CTCAE 5.0 grade evaluation grade 1 and below (except for no effect). The central nervous system metastasis without treatment or with clinical symptoms is not suitable for the group according to the judgment of the researcher; the patients suspected of brain or pia mater diseases with clinical symptoms need to be excluded by CT / MRI (flow chart notes); Uncontrolled systemic infection; Have a history of immunodeficiency, including HIV antibody test; Treponema pallidum antibody positive; Patients with chronic hepatitis B virus (HBV) infection, and the number of copies of HBV is more than 1000 IU / ml; patients with active hepatitis C virus (HCV) infection (note of index flow chart); Serious cardiovascular disease history: including ventricular arrhythmia requiring clinical intervention; acute coronary syndrome, congestive heart failure, stroke or other cardiovascular events of level III and above within 6 months; NYHA heart function grade ≥ level II or left ventricular ejection fraction (LVEF) < 50%; poor control of hypertension, which is judged to be uncomfortable by researchers Join group; Patients with other serious systemic diseases (including respiratory system, endocrine system, etc.) who are not suitable for clinical trials according to the judgment of researchers; Known dependence on alcohol or drugs; People with mental disorder or poor compliance; Pregnant or lactating women; In the past, when using biological products drugs, severe transfusion reaction occurred; The investigator believes that the subject is not suitable for this clinical study due to any clinical or laboratory examination abnormality or other reasons.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: anti-EGFR monoclonal antibody<br>Single-dose Phase:This is a dose-escalation trial, all participants will receive treatment with CDP1. Participants enrolled in this trial may receive one of the following doses dependent upon time of enrolment into the study. Cohort 1:400mg/m2;Cohort 2: 500mg/m2;Cohort 3: 750mg/m2; Multi-dose Phase:Multiple administrations of three Cohorts of subjects were followed by continuous administration of CDP1. | Drug: CDP1<br>* Single-dose Phase: Cohort 1:400mg/m2;Cohort 2: 500mg/m2;Cohort 3: 750mg/m2; Multi-dose Phase:Cohort 1 Dosing regimen is the first administration of 400mg/m2, followed by 250mg/m2/W;Cohort 2,3 Dosing regimen is the first administration of 500mg/m2, followed by 500mg/m2/2W.<br>* Other names: Recombinant anti-EGFR human mouse chimeric monoclonal antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose Limiting Toxicities (DLT) | Number of participants with dose limiting toxicity (DLT) | At the end of Cycle 1 (28 days). | 
| Recommended phase II dose (RP2D) | Recommended phase II dose (RP2D) evaluated on the first cycle. | At least one cycle of treatment(6 months). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic parameters: Observed Maximum Serum Concentration (Cmax) of CDP1 After Infusion | Pharmacokinetic parameters Cmax for CDP1 | Up to 28 Days | 
| Pharmacokinetic Parameters: Area Under the Serum Concentration-time Curve From Time Zero to the Last Sampling Time (AUC0-t) After Infusion AUC(0-t) for CDP1 | AUC(0-t) for CDP1 | Up to 28 Days | 
| Pharmacokinetic parameters: Area Under the Serum Concentration-time Curve From Time Zero to Infinity (AUC0-00) After Infusion Pharmacokinetic parameters: AUC(0-00) for CDP1 | Pharmacokinetic parameters: AUC(0-00) for CDP1 | Up to 28 Days | 
| Pharmacokinetic parameters: Apparent Terminal Half-life (t1/2) of CDP1 After Infusion | Pharmacokinetic parameters T1/2 for CDP1 | Up to 28 Days | 
| Immunogenicity indicators: Number of participants with positive anti-drug antibodies (ADA) | Immunogenicity indicators: Number of participants with positive anti-drug | an average of 6 months | 
| Immunogenicity indicators: Number of participants with positive neutralizing antibodies | Immunogenicity indicators: Number of participants with positive neutralizing antibodies | an average of 6 months | 
| Objective response rate (ORR) | The ORR is defined as the proportion of subjects with confirmed CR or confirmed PR, based on RECIST Version 1.1. | an average of 6 months | 
| Progression-free survival (PFS) | Progression-free survival is defined as the time from the start of treatment with CDP1 until the first documentation of disease progression or death due to any cause, whichever occurs first. | an average of 6 months |