SHR-1210 in Combination With BP102 and XELOX in Patient With Metastatic Colorectal Cancer

Study Overview
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Brief Summary
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This is an open label, single-arm, multi-center, phase II study of SHR-1210 in metastatic colorectal cancer patients with the recurrent lesion(s) post-surgery or the untreated mCRC. SHR-1210 is a humanized monoclonal antibody against Programmed death 1(PD-1).BP102 is a humanized recombinant monoclonal IgG1 antibody. The primary objective of this study is to investigate the safety and efficacy of the subjects who given the combination therapy.

Official Title
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SHR-1210，a Novel Anti-pd-1 Antibody, in Combination With BP102,a Biosimilar of Bevacizumab, and XELOX, (Oxaliplatin Plus Capecitabine) in Patient With Metastatic Colorectal Cancer: a Single-arm, Open Label, Multi-center, Phase II Study

Conditions
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Metastatic Colorectal Cancer

Intervention / Treatment
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* Drug: SHR-1210
* Drug: BP102
* Drug: oxaliplatin
* Drug: capecitabine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 and ≤75 years old; Histologically confirmed colorectal cancer with a metastatic / recurrent lesion that cannot be cured by surgery. At least one measurable lesion have been the confirmatory detection respect to RECIST 1.1 No prior first-line systemic anti-tumor therapy for mCRC (including systemic chemotherapy, molecular targeted therapy, biotherapy, immunotherapy, radiotherapy, local therapy and other study treatment) have been identified At least 6 months have elapsed if considering the interval from the time of firstly documented metastasis to the post-operational adjuvant chemotherapy termination Can provide either a newly obtained or archival tumor tissue sample. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 Life expectancy ≥ 3 months Subjects must have normal organ and marrow function as defined below: Absolute neutrophil count (ANC) ≥1,500 /mm3（1.5×109 /L） Platelets ≥90,000 / mm3（90×109 /L） Hemoglobin ≥10 g/dL, within the 2 weeks prior to the screening no need for the transfusion Serum albumin ≥2.8 g/dL Total bilirubin≤ 1.5 X ULN, AST (SGOT), ALT (SGPT) ≤ 2.5 X ULN (AST/ALT ≤ 5 X ULN if liver metastatic); Creatinine clearance ≥ 50 mL/min according to Cockcroft-Gault formula For females of child bearing potential, a negative urine or serum pregnancy test result within 72h before study treatment. Participants of reproductive potential must be willing to use adequate contraception for the course of the study until 3 months after the last dose of any of the drugs in the study. The subjects are accredited with good compliance, signed the informed consent, and capable to cooperate, completing the relevant examination and follow-ups. Exclusion Criteria: Prior first-line systemic anti-tumor therapy for mCRC (including systemic chemotherapy, molecular targeted therapy, immunotherapy, biotherapy, and other treatment). The metastatic/recurrent lesion is subject to be cured by surgical intervention. Major operation or open biopsy or major trauma within 4 weeks prior to first dose. Known Cerebral and/or leptomeningeal metastasis. Bleeding predisposition, high bleeding risk or coagulant disorder, thrombotic event(s) occurrence ≤6 months and/or hemoptysis ≤3 months (≥ 1/2 teaspoons fresh blood each) prior to the screening; use of full dose oral or parenteral anticoagulant or thrombolytic medication (allowing preventative anticoagulation); use of aspirin (> 325 mg/day) or other platelet-inhibition non-steroidal anti-inflammatory drugs within 10 days since the screening; CT/MRI imaging evidence, testimony of the main arteries/veins (such as pulmonary artery or superior vena cava) being infringed, encroached Subjects with uncontrolled hypertension and with a medical history of hypertensive crisis or hypertensive encephalopathy; serious cardiovascular and cerebrovascular diseases, including cerebrovascular accident (CVA) ≤6 months before the screening, transient ischemic attack (TIA), myocardial infarction and significant vascular disease (including but not limited to aortic aneurysms with need for surgical repair or recent evidence of arterial thrombosis), unstable angina, heart failure and serious arrhythmias that are uncontrolled by drugs (New York Heart Association Class ≥2). Subjects with non-healing wounds, active peptic ulcer or fracture and active infection; tracheal esophageal fistula, gastrointestinal perforation or gastrointestinal fistula and abdominal abscess in the 6 months prior to the screening. Subjects with any active autoimmune disease or history of autoimmune disease Active infection or an unexplained fever > 38.5°C before two weeks of randomization (subjects with tumor fever may be enrolled at the discretion of the investigator); History of Interstitial Pneumonia or received Corticosteroids for non-infectious pneumonitis. Known Human Immunodeficiency Virus (HIV) infection、active Hepatitis B or Hepatitis C. Known history of hypersensitivity to macromolecular protein preparation or any components of the SHR-1210 or BP102 formulation, allergy, hypersensitivity, or contraindication to oxaliplatin, or Capecitabine Currently participating or has participated in a study within 4 weeks of the first dose of study medication. Has a known additional malignancy within the last 5 years before study treatment with the exception of curatively treated basal cell and squamous cell carcinoma of the skin and/or curatively resected in-situ cervical and/or breast cancers Received a live vaccine within 4 weeks of the first dose of study medication Pregnancy or breast feeding. According to the investigator, other conditions that may lead to stop the research.

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: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SHR-1210+BP102+XELOX<br>Participants receive SHR-1210 200mg,BP102 7.5mg/kg and oxaliplatin 130mg/m2 in day 1 intravenously every 3week, capecitabine by oral bid in day1-14 every 3 week until disease progression or unacceptable toxicity | Drug: SHR-1210<br>* 200mg<br>Drug: BP102<br>* 7.5mg/kg<br>Drug: oxaliplatin<br>* 130mg/m2<br>Drug: capecitabine<br>* 1000mg/m2<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of the combination therapy: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment | From sign icf to the end of follow-up | 24 months | 
| Objective response rate | From sign icf to occurrence of objective response (complete regression (CR) and partial regression (PR) need to be confirmed 28 days after the occurrence) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| DOR | Duration of response ,DOR | 24 months | 
| DCR | Disease Control Rate，DCR | 24 months | 
| PFS | Progression free survival,PFS | 24 months | 
| 9month PFS rate | Month 9 PFS rate,PFS9m | 9 months | 
| 12month and 24 month OS rate | Overall survival rate: the time from the date of icf to the date of documented clinical or radiological progression or death due to any cause within 12 and 24 months after first visit | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SHR-1210, Phase II, BP102