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
Overview
- Phase
- Phase 2
- Intervention
- SHR-1210
- Conditions
- Metastatic Colorectal Cancer
- Sponsor
- Jiangsu HengRui Medicine Co., Ltd.
- Enrollment
- 12
- Locations
- 1
- Primary Endpoint
- Safety of the combination therapy: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
- Status
- Terminated
- Last Updated
- 6 years ago
Overview
Brief Summary
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.
Investigators
Eligibility Criteria
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）
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.
Arms & Interventions
SHR-1210+BP102+XELOX
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
Intervention: SHR-1210
SHR-1210+BP102+XELOX
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
Intervention: BP102
SHR-1210+BP102+XELOX
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
Intervention: oxaliplatin
SHR-1210+BP102+XELOX
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
Intervention: capecitabine
Outcomes
Primary Outcomes
Safety of the combination therapy: Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Time Frame: 24 months
From sign icf to the end of follow-up
Objective response rate
Time Frame: 24 months
From sign icf to occurrence of objective response (complete regression (CR) and partial regression (PR) need to be confirmed 28 days after the occurrence)
Secondary Outcomes
- DOR(24 months)
- DCR(24 months)
- PFS(24 months)
- 9month PFS rate(9 months)
- 12month and 24 month OS rate(24 months)