Safety and Efficacy of Recombinant Anti-EGFR Monoclonal Antibody in Patients With Wild-type RAS and BRAF mCRC

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of recombinant anti-EGFR Monoclonal antibody（SCT200）in patients with wild-type RAS and BRAF mCRC treated with fluorouracil, oxaliplatin and irinotecan after failure of standard therapy

Official Title
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Recombinant Anti-EGFR Monoclonal Antibody（SCT200） in Patients With Chemotherapy- Refractory Wild Type RAS and BRAF Metastatic Colorectal Cancer

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Biological: Recombinant Anti-EGFR Monoclonal Antibody（SCT200）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to provide written informed consent and can understand and comply with the requirements of the study; Men and women ≥ 18 years of age; Life expectancy of longer than 3 months ( clinical assessment); With an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 1; Have been diagnosed as mCRC verified histologically; Patients treated with fluorouracil, oxaliplatin and irinotecan after failure of standard therapy. Disease progressed or developed non-tolerable toxicity after systemic chemotherapy：a. at least one treatment cycle should be completed, and maintenance therapy using one of the doublets is considered as the same line of therapy ; b. May have received adjuvant therapy for primary colorectal cancer provided that at least 6 months have elapsed from the time the adjuvant therapy was concluded and recurrent disease was documented; RAS and BRAF wildtype status of primary colorectal cancer or related metastasis; Adequate organ and marrow function as defined below: Absolute neutrophil count (ANC) greater than/equal to 1.5×l09/L; Platelets greater than/equal to 75×109/L; Hemoglobin greater than/equal to 80g/L; Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) less than/equal to 2.5 times IULN, or less than/equal to 5 times IULN if known liver metastases; Total bilirubin less than/equal to 1.5 within institutional upper limit of normal (IULN); Serum creatinine less than/equal to 1.5 times IULN; Electrolyte: magnesium greater than/equal to normal. According to RECIST 1.1 , patients must have at least one measurable lesion that can be accurately assessed at baseline and is suitable for repeated assessment by CT, MRI. Longest diameter greater than/equal to10mm（CT scan slice thickness no greater than 5 mm）, a lymph node must be ≥15mm in short axis when assessed by CT scan. Exclusion Criteria: Patient with active brain metastasis or indicated for symptomatic treatment for brain metastasis, untreated with proper radiation therapy, showing clinical symptoms or symptom stable time less than 28 days; Patients with other primary malignancies within the past 5 years except non-melanoma skin cancer, carcinoma in situ of cervix or prostatic intraepithelial neoplasia; Patients who are allergic to analogue of SCT200 and/or its inactive ingredients; Patients administrated EGFR target treatment including EGFR TKI agent or anti- EGFR monoclonal antibody; Within 4 weeks, patients received anti-tumor drugs (such as chemotherapy, hormone therapy, immune therapy, the antibody therapy, radiotherapy) or research drugs, or patients with grade 2 or more adverse reaction caused by previous anti-tumor therapy(except alopecia or neurotoxicity grade 2 or less); Patients are currently enrolled in other research devices or in research drugs, or less than 4 weeks from other research drugs or devices. Patients received major surgery(such as need general anesthesia ) within 4 weeks , should recover from the injury associated with the surgery. Patients treated with EPO, G-CSF or GM-CSF. Patients who have clinically significant cardiovascular disease (defined as unstable angina pectoris, symptomatic congestive heart failure (NYHA, greater than II), uncontrollable severe arrhythmia); Patients occurred myocardial infarction within 6 months. Patients who have interstitial lung disease, such as interstitial pneumonia, pulmonary fibrosis, or CT or MRI reminder ILD . Patients with clinical symptoms, required clinical intervention or stable time less than 4 weeks of serous cavity effusion (such as pleural effusion and ascites); Patients with serious psychological or psychiatric disorders which may affect subject compliance in this clinical study; Pregnant or lactating women, or women who planned to be pregnant within 6 months of treatment; Patients who were not willing to accept effective contraceptive measures (including male or female subjects) during treatment and within 6 months after treatment; Patients with active hepatitis B or active hepatitis C, etc. (for patients with a history of hepatitis B, whether treated or not, HBV DNA ≥104 or ≥ 2000IU/ml, HCV RNA≥15IU/ml); HIV antibody positive (if there is no clinical evidence suggesting that there may be HIV infection, there is no need to detect); Patients with uncontrolled active infections before enrollment 2 weeks (except simple urinary tract infection or upper respiratory tract infection); Patients have alcohol or drug addiction; Inability to comply with study and/or follow-up procedures

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Interventional Model Description: Treated with recombinant anti-EGFR Monoclonal antibody（SCT200）until disease progression
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: recombinant anti-EGFR monoclonal antibody（SCT200）<br>Initially, 6.0mg/kg of SCT200 will be administered once a week for a maximum of 6 cycles. After 6 cycles, 8.0mg/kg of SCT200 will be administered every two weeks until disease progression. | Biological: Recombinant Anti-EGFR Monoclonal Antibody（SCT200）<br>* Experimental: recombinant anti-EGFR monoclonal antibody（SCT200） Recombinant Anti-EGFR Monoclonal Antibody（SCT200）. Initially, SCT200 6.0mg/kg will be administered at day 1 every week for a maximum of 6 cycles. After 6 cycles SCT200 8.0mg/kg will be administered at day 2 every weeks until disease progression.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate | The achievement of either a partial response (PR) or complete response (CR), according to RECIST 1.1 criteria | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate - left side | The achievement of either a partial response (PR) or complete response (CR), left side mCRC patients treated by SCT200. according to RECIST 1.1 criteria | 1 year | 
| Best of response | Number of patients in each response category（CR, PR, SD, PD）, according to RECIST 1.1 criteria | 1 year | 
| Duration of response | Defined as the time from the date that the response criteria are first met to the date that progressive disease (PD) is objectively documented or death, whichever occurs first. | 1 year | 
| Disease control rate | The achievement of any a stableresponse（SD）, partial response (PR) or complete response (CR), according to RECIST 1.1 criteria | 1 year | 
| Time to response | Defined as the time from first dose of SCT200 to documentation of a response.according to RECIST 1.1 criteria | 1 year | 
| Progression free survival | Defined as time from first dose of SCT200 until first documentation of Progression or death, whichever comes first， according to RECIST 1.1 criteria | 1 year | 
| Overall survival | Defined as the time from first dose of SCT200 until death. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Full human anti-EGFR monoclonal antibody (SCT200), metastatic colorectal cancer （mCRC）