Safety and Tolerability Evaluation Study of BVAC-B in Patients With HER2/Neu(Human Epithelial Growth Factor Receptor 2) Positive Gastric Cancer After Failure to Standard Care

Study Overview
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Brief Summary
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BVAC-B is immunotherapeutic vaccine using B-Cell and Monocytes as antigen presenting cell. This study is Open-label, Accelerated titration, Multiple dosing study to evaluate the safety, tolerability, immune response and pre-efficacy of BVAC-B in patients with progressive or recurrent HER2/neu positive gastric cancer after failure to standard care. 9-27 patients will be enrolled.

Official Title
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Single Center, Open-label, Accelerated Titration, Multiple Dosing Study to Evaluate the Safety, Tolerability, Immune Response and Pre-efficacy of BVAC-B in Patients With Progressive or Recurrent HER2/Neu Positive Gastric Cancer After Failure to Standard Care

Conditions
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Stomach Neoplasms

Intervention / Treatment
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* Biological: BVAC-B


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Progressive or recurrent HER2/neu positive(IHC 1+≥) gastric cancer Received 1 or more chemotherapy or radiotherapy as prior therapy for progressive or recurrent tumor lesion At least 1 measurable lesion according to RECIST(ver 1.1) Ages above 19 ECOG performance status between 0 to 2 Patients meets the blood test standards in the screening test Patients meets the blood chemistry test standards in the screening test Patients who has agreed to a medically accepted contraceptive in this clinical trial Patients at least six months or more of survival can be expected Patients decided to participate in this clinical trial and signed written informed consent Exclusion Criteria: Histopathology is a neuroendocrine or small cell carcinoma History of brain metastasis or signs of brain metastasis Clinical diagnosis of hepatitis C or hepatitis B Clinical diagnosis of human immunodeficiency virus (HIV) History of HIV infection Patients with heart failure, coronary artery disease(CAD) or Myocardial infarction in 6 month prior to screening. (LVEF is lower than 50% in screening visit) Administered the drug for other clinical trials within 4weeks before participate in this trial Administered any vaccines within 4weeks before participate in this trial (4 weeks for live vaccine, 2 weeks for other inactivated vaccine) Administered the granulocytes concentrates within 3 months before the screening visit Received chemotherapy or radiation therapy within 2 weeks before the 1st administration of investigational drug(BVAC-B) Received following formulation within 1 months before the screening visit : Chronic steroids(more than 5 days), immunosuppressant or immunomodulatory agents. G-CSF Patients who have participated in the clinical trial of a immunotherapeutic vaccine within 1 year or immunotherapy within 3 months before the screening visit Patients who is pregnant or breast-feeding Patients who researchers has determined that participation in the clinical trial is inappropriate Suspected to have other progressive cancer or malignant tumor needs treatment in 3 years. Completely treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, thyroid carcinoma, cervical intraepithelial neoplasia are not included

Ages Eligible for Study
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Minimum Age: 19 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: Accelerated titration
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BVAC-B<br>BVAC-B IV injection at 0, 4, 8, 12nd weeks. | Biological: BVAC-B<br>* Autologous B cell and monocyte presenting HER2/neu antigen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate Maximum tolerated dose(MTD) for phase 2 trial | Find Serious adverse drug reaction(Grade 3) | End of Dose-escalation stage(7 month from study start, Estimated) | 
| Incidence of Serious Adverse Events assessed with CTCAE v4.03 | Evaluate safety and tolerability | 14th week from first injection | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokine | Measure Interferon(IFN)-r, Interleukin(IL)-4 | Screening visit, Visit 2 (0 week) , visit 4 (4 week) ,visit 5 (6 week), visit 6 (8 week), visit 8(12 week), Termination visit(16 week) | 
| HER2/neu specific antibody | Measure HER2/neu specific antibody concentration | Screening visit, every 2 weeks after 1st injection(till 16th week) | 
| NKT/NK cell assay | Measure NKT/NK cell activity | Screening visit, every 24hr after injection(up to 12th week) | 
| CD4/CD8 assay | Measure CD4/CD8 T cell activity | Screening visit, every 2 weeks after 1st injection(up to 16th week) | 
| Lymphocyte subset | Measure change of lymphocyte subset | Screening visit, visit 4 (4 week), visit 6 (8 week), visit 8 (12 week), termination visit (16 week) | 
| Change of tumor burden | Measure change of tumor burden by CT/MRI to determine pre-effecacy | Screening visit, Termination visit(16th week) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HER2/neu, IHC 1+, BVAC, Cellid, B-cell, Monocyte, Immunotherapeutic vaccine, Breast cancer, Colorectal cancer, Pancreatic cancer