EBV-positive Nasopharyngeal CarcinomaPhase 1NCT05864924
A Phase 1 Study of BRG01 in Subjects With Relapsed/Metastatic Epstein-Barr Virus (EBV)-Positive Nasopharyngeal Carcinoma
A Phase 1 study testing Cohort A: 3.0x10^6 CAR-T cells/kg, Cohort B: 9.0x10^6CAR-T cells/kg and Cohort C:1.5x10^7 CAR-T cells /kg in people with EBV-positive Nasopharyngeal Carcinoma, run by BioSyngen Pte Ltd at 1 site in China.
Trial summary
Phase 1 study evaluating the safety and efficacy of BRG01 in subjects with relapsed/ metastatic EBV-positive nasopharyngeal carcinoma (NPC). BRG01 is a Chimeric Antigen Receptor T-Cell therapy targetting on the specific protein of EBV, which is expressed on the EBV associated cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- EBV-positive Nasopharyngeal Carcinoma
- What is being tested?
- Cohort A: 3.0x10^6 CAR-T cells/kg, Cohort B: 9.0x10^6CAR-T cells/kg and Cohort C:1.5x10^7 CAR-T cells /kg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteChina
- Study dates
- 10 May 2023to 26 Apr 2024
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed nasopharyngeal carcinoma;
- Be able to understand this study and have signed the informed consent;
- Age >18 years old, <75 years old;
- Expected survival period ≥3 months;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
- Epstein-Barr virus Encoded RNAs (EBER) positive in tumor tissue detected by in situ hybridization (ISH or FISH):
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- By immunohistochemistry (IHC), the target in the pathological sample of the tumor tissue is positive and >20%;
- According to RECIST v1.1, there is at least one measurable lesion;
- Patients must have failed to response at least 2 lines of the standard therapies recommended by local NPC guidance, and without other therapy available.
- Venous access for apheresis or blood collection can be established, without contraindications for leukapheresis;
- Having adequate organ and bone marrow function, as defined below:
- Complete Blood Count Neutrophils (NEUT#) ≥1.0x10^9/L; Platelet (PLT) ≥80x10^9/L; Hemoglobin ≥90g/L; Liver function: Without No liver metastasis Aspartate aminotransferase (AST) ≤2.5 x Upper Limit of Normal (ULN); Alanine aminotransferase (ALT) ≤2.5 x ULN; Total bilirubin (TBIL) ≤1.5 x ULN; Liver Function: With liver metastasis Aspartate aminotransferase (AST) ≤5 x ULN; Alanine aminotransferase (ALT) ≤5 x ULN; Liver Function: With liver metastasis or Gilbert syndrome; Total bilirubin (TBIL) ≤2 x ULN; Creatinine Clearance Rate (CCR) ≥ 50 mL/min; International Normalized Ratio (INR) ≤1.5xULN; Activated partial thromboplastin time (APTT) ≤1.5xULN;
- 12. During the study period and within 6 months after the end of administration, the subjects of childbearing potential (whether male or female) must use effective medical contraceptive measures For female subjects of childbearing age, a pregnancy test must be performed within 72 hours before cell infusion, and the result is negative.
- -
Who cannot join
- Known or suspected being allergy to any of the agents used in this study.
- Previously received anti-tumor treatments, including other anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents, hormone therapy, radiation therapy (except local radiation therapy for pain relief), etc., the treatment related toxicity not recovered to baseline or CTCAE≤0~1.
- Received adoptive cellular immunotherapy (including CAR-T cells and T Cell Receptor-T cells (TCR-T)) within 6months.
- Confirmed central nervous system metastasis.
- Confirmed extensive liver metastasis (the tumor volume is estimated to be≥50% of the total liver volume imaging).
- Clinically significant active infections (e.g. Simple Urinary Tract Infection (UTl), bacterial pharyngitis are allowed) or currently receiving IV antibiotics or have received IV antibiotics with in 14 days prior to enrollment(Prophylaxis antibiotics, antivirals and antifungals are permitted);
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- HBsAg positive and Hepatitis B Virus (HBV) DNA copy number positive (quantitative detection ≥1000cps/ml), Hepatitis C Virus (HCV) antibody positive and HCV RNA positive, or HIV positive.
- History of autoimmune diseases (e.g, primary immunodeficiency, inflammatory bowel disease. idiopathic thrombocytopenic purpura, systemic lupus erythematosus, autologous hemolytic anemia, rheumatoid arthritis, etc.).
- The following diseases have not been resolved to CTCAE grade 0-1, 7 days before the conditioning chemotherapy, including: dyspnea, diarrhea, acute or chronic pancreatitis.
- New York Heart Association (NYHA) class 3 or 4.
- Symptoms and sign of cardiovascular diseases, e.g., cardiovascular ischemia, arrhythmias, and heart failure.
- Symptoms and signs of cerebrovascular accidents.
- History of other malignant tumors that cannot be cured within 3 years, except for cervical cancer in situ or skin basal cell carcinoma, and other malignant tumors with a disease-free survival period of more than 5 years.
- Current or expected need for long-term systemic corticosteroid therapy. Note: Topical and inhaled corticosteroids in standard doses and physiologic replacement for subjects with adrenal insufficiency are allowed. Doses of corticosteroids of greater than or equal to 5 mg/day of prednisone or equivalent doses of other corticosteroids are not allowed.
- Subjects of both genders who are not willing to practice birth control from the time of consent through 6 months after the completion.-
- Subjects have experienced major surgery or severe trauma within 4 weeks before enrollment or are expected to undergo major surgery during the study period.
- Combined with graft versus host disease (GVHD).-
- Women of child-bearing potential who are pregnant or breastfeeding at the screening. Females who have undergone surgical sterilization or who have been postmenopausal for at least 2 years are not considered to be of childbearing potential.
- Patients with confirmed history of neurological or psychotic disorders, including epilepsy, seizure, dementia.
- Any other condition that, in the discretion of the investigator, will make subjects exposed to unnecessary risks or not compliance to participation in this clinical study.
- -
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1 Study Evaluating the Safety and Efficacy of BRG01 in Subjects With Relapsed/Metastatic EBV-positive Nasopharyngeal Carcinoma
Phase 1 study evaluating the safety and efficacy of BRG01 in subjects with relapsed/ metastatic EBV-positive nasopharyngeal carcinoma (NPC).
BRG01 is a Chimeric Antigen Receptor T-Cell therapy targetting on the specific protein of EBV, which is expressed on the EBV associated cancer cells.
Read more
This study adopts the traditional "3+3" dose escalation design. Approximately12~18 EBV+ NPC subjects will be enrolled to evaluate the safety of BRG01. An internal safety review team (SRT) will review the safety data and make recommendations on further study conduct and progression to subsequential cohorts.
Subjects will be enrolled into 3 cohorts of different doses, designated as cohort A, B and C.Cohort A: 3.0x10^6 CAR-T cells/kg,3 subjects, Cohort B: 9.0x10^6 CAR-T cells/kg,3 subjects, and Cohort C:1.5x10^7 CAR-T cells /kg, 6 subjects,respectively.
Subjects in each cohort will follow the same treatment schedule and procedural requirements.
Read the detailed description
Primary Objective:
To evaluate the safety and efficacy of BRG01.
Secondary Objectives:
- To evaluate the pharmacokinetics (PK)，pharmacodynamics (PD) and immunogenicity of BRG01.
- To evaluate the preliminary efficacy of BRG01 in patients with relapsed/metastatic EBV+ NPC.
Exploratory Objectives:
- To explore the correlation between the proliferation and persistence of BRG01 cells in vivo and the efficacy.
- To explore the correlation between target expression level in tumor tissue with the safety and efficacy.
- To explore the correlation between plasma EBV DNA level with safety and efficacy.
- Conditions
- EBV-positive Nasopharyngeal Carcinoma
- Being tested
- Cohort A: 3.0x10^6 CAR-T cells/kg, Cohort B: 9.0x10^6CAR-T cells/kg, Cohort C:1.5x10^7 CAR-T cells /kg
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cohort A: 3.0x10^6 CAR-T cells/kgBiological
Intravenous infusion
Cohort B: 9.0x10^6CAR-T cells/kgBiological
Intravenous infusion
Cohort C:1.5x10^7 CAR-T cells /kgBiological
Intravenous infusion
| Study group | Role | What they receive |
|---|---|---|
| BRG01 injection | Experimental | Intravenous infusion Receives: Biological: Cohort A: 3.0x10^6 CAR-T cells/kg; Biological: Cohort B: 9.0x10^6CAR-T cells/kg; Biological: Cohort C:1.5x10^7 CAR-T cells /kg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-Limiting Toxicity (DLT)
Incidence of adverse events defined as Dose-Limiting Toxicity (DLT).
Measured: From the infusion (Day 0) to Day 28
Maximum tolerated dose
The maximum CAR-T dose that can be tolerated in the study.
Measured: From the infusion (Day 0) to Day 28
AE, SAE, AESI, CRS, ICANS, TEAE
The incidence of adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI), cytokine release syndrome (CRS) immune cell associated neurotoxicity syndrome (ICANS) and treatment-emergent adverse events (TEAE).
Measured: The day of leukapheresis to 3 months after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 May 2023
- Study start10 May 2023
- Primary completion26 Apr 2024
- Study completion26 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EBV-positive Nasopharyngeal CarcinomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- BioSyngen Pte Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05864924
- Sponsor's protocol ID
- BIOSG-BRG-01
- Status last verified
- Apr 2023
- First submitted
- 27 Apr 2023
- Last updated
- 8 May 2024
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study Evaluating the Safety and Efficacy of BRG01 in Subjects With Relapsed/Metastatic EBV-positive Nasopharyngeal Carcinoma
- ClinicalTrials.gov ID
- NCT05864924
- Acronym / sponsor ID
- BIOSG-BRG-01
- Conditions
- EBV-positive Nasopharyngeal Carcinoma
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- BioSyngen Pte LtdIndustry (pharma, biotech, devices)
- Study start
- 10 May 2023 (actual)
- Primary completion
- 26 Apr 2024 (actual)
- Study completion
- 26 Apr 2024 (actual)
- First posted
- 18 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase 1 study evaluating the safety and efficacy of BRG01 in subjects with relapsed/ metastatic EBV-positive nasopharyngeal carcinoma (NPC).
BRG01 is a Chimeric Antigen Receptor T-Cell therapy targetting on the specific protein of EBV, which is expressed on the EBV associated cancer cells.
This study adopts the traditional "3+3" dose escalation design. Approximately12~18 EBV+ NPC subjects will be enrolled to evaluate the safety of BRG01. An internal safety review team (SRT) will review the safety data and make recommendations on further study conduct and progression to subsequential cohorts.
Subjects will be enrolled into 3 cohorts of different doses, designated as cohort A, B and C.Cohort A: 3.0x10^6 CAR-T cells/kg,3 subjects, Cohort B: 9.0x10^6 CAR-T cells/kg,3 subjects, and Cohort C:1.5x10^7 CAR-T cells /kg, 6 subjects,respectively.
Subjects in each cohort will follow the same treatment schedule and procedural requirements.
Detailed description
Primary Objective:
To evaluate the safety and efficacy of BRG01.
Secondary Objectives:
- To evaluate the pharmacokinetics (PK)，pharmacodynamics (PD) and immunogenicity of BRG01.
- To evaluate the preliminary efficacy of BRG01 in patients with relapsed/metastatic EBV+ NPC.
Exploratory Objectives:
- To explore the correlation between the proliferation and persistence of BRG01 cells in vivo and the efficacy.
- To explore the correlation between target expression level in tumor tissue with the safety and efficacy.
- To explore the correlation between plasma EBV DNA level with safety and efficacy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BRG01 injection | Experimental | Biological: Cohort A: 3.0x10^6 CAR-T cells/kg, Biological: Cohort B: 9.0x10^6CAR-T cells/kg, Biological: Cohort C:1.5x10^7 CAR-T cells /kgIntravenous infusion |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Histologically confirmed nasopharyngeal carcinoma;
- Be able to understand this study and have signed the informed consent;
- Age >18 years old, <75 years old;
- Expected survival period ≥3 months;
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
Key exclusion criteria (21 listed)
- Known or suspected being allergy to any of the agents used in this study.
- Previously received anti-tumor treatments, including other anti-tumor investigational drugs, chemotherapy, immunotherapy, biological agents, hormone therapy, radiation therapy (except local radiation therapy for pain relief), etc., the treatment related toxicity not recovered to baseline or CTCAE≤0~1.
- Received adoptive cellular immunotherapy (including CAR-T cells and T Cell Receptor-T cells (TCR-T)) within 6months.
- Confirmed central nervous system metastasis.
- Confirmed extensive liver metastasis (the tumor volume is estimated to be≥50% of the total liver volume imaging).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cohort A: 3.0x10^6 CAR-T cells/kgIntravenous infusion | Biological | BRG01 injection |
| Cohort B: 9.0x10^6CAR-T cells/kgIntravenous infusion | Biological | BRG01 injection |
| Cohort C:1.5x10^7 CAR-T cells /kgIntravenous infusion | Biological | BRG01 injection |
Primary outcome
Dose-Limiting Toxicity (DLT)
Time frame: From the infusion (Day 0) to Day 28
Incidence of adverse events defined as Dose-Limiting Toxicity (DLT).
Maximum tolerated dose
Time frame: From the infusion (Day 0) to Day 28
The maximum CAR-T dose that can be tolerated in the study.
AE, SAE, AESI, CRS, ICANS, TEAE
Time frame: The day of leukapheresis to 3 months after infusion
The incidence of adverse events (AE), serious adverse events (SAE), adverse events of special interest (AESI), cytokine release syndrome (CRS) immune cell associated neurotoxicity syndrome (ICANS) and treatment-emergent adverse events (TEAE).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cohort A: 3.0x10^6 CAR-T cells/kg, Cohort B: 9.0x10^6CAR-T cells/kg and Cohort C:1.5x10^7 CAR-T cells /kg in people with EBV-positive Nasopharyngeal Carcinoma, run by BioSyngen Pte Ltd at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 May 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-Limiting Toxicity (DLT) (time frame: From the infusion (Day 0) to Day 28). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2024.