B7-H3-positive Relapsed/ Refractory NeuroblastomaPhase 1NCT05562024
TAA06 Injection in the Treatment of Patients With B7-H3-positive Relapsed/ Refractory Neuroblastoma
A Phase 1 study testing T cell injection targeting B7-H3 chimeric antigen receptor in people with B7-H3-positive Relapsed/ Refractory Neuroblastoma, run by PersonGen BioTherapeutics (Suzhou) Co., Ltd. at 2 sites in China.
Trial summary
Phase I clinical trials are designed as open-label, dose-escalation and dose-expansion clinical studies, the main purpose of which is to explore the tolerability, safety, cytokinetic characteristics and RP2D and preliminary observation of the efficacy of the study drug in subjects with B7-H3-positive… Read more about this study
- Who is it for?
- Ages 1 year and older
- Conditions the study is for
- B7-H3-positive Relapsed/ Refractory Neuroblastoma
- What is being tested?
- T cell injection targeting B7-H3 chimeric antigen receptor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesChina
- Study dates
- 30 Dec 2022to 18 Feb 2039
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 1 year and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 1 year (including cut-off value), gender is not limited
- Expected survival time ≥ 3 months
- Karnofsky score (> 16 years) or Lansky score (≤ 16 years) > 60 points
- Meet the clinical diagnostic criteria and be diagnosed as recurrent / refractory neuroblastoma. For first-line standard treatment, please refer to the consensus of experts in the diagnosis and treatment of Pediatric Neuroblastoma (Chinese Journal of Pediatric surgery, Volume 36, No. 1, 2015), the guidelines for the diagnosis and treatment of Pediatric Neuroblastoma of 2019 by the Health Commission, and the consensus of experts in the diagnosis and treatment of Pediatric Neuroblastoma (CCCG-NB-2021 Program) (Chinese Journal of Pediatric surgery, Volume 43, No. 7, 2022)
- Recurrence is defined as the determination of recurrence after remission after at least first-line standard treatment.
- Refractory is defined as a person who is not in remission after at least 4 cycles of chemotherapy (≥ 2 chemotherapeutic drugs, including alkylating agents and platinum)
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- The tumor tissue samples of the subjects were stained by immunohistochemistry (IHC) to show that the expression intensity of B7-H3 on the surface of tumor cell membranes was 1+ or above, and the proportion of positive staining of tumor cell membranes was ≥1%
- At least one measurable lesion defined by RECISTv1.1 criteria, and at least one lesion that can be irradiated (except bone marrow)
- Subjects with lesions only in the bone marrow may also be enrolled (without irradiation)
- Liver and kidney function, cardiopulmonary function must meet the following requirements:
- Total bilirubin ≤ 3 × ULN;ALT and AST ≤ 5 × ULN
- Creatinine≤2 ULN
- Left ventricular ejection fraction ≥ 50%
- Blood oxygen saturation ≥ 92%
- Patients and/or their guardians understand the trial and have signed informed consent
Who cannot join
- Patients who were judged by the investigator to require long-term immunosuppressive therapy at the time of screening
- Cerebrovascular accident or seizure occurred within 6 months before signing the informed consent
- Malignant tumors other than neuroblastoma, excluding carcinoma in situ
- Hepatitis B surface antigen (HBsAg) positive; hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection not within the normal reference range; hepatitis C virus (HCV) antibody positive and peripheral blood type C Hepatitis virus (HCV) RNA positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA positive; syphilis positive
- Serious cardiac disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia
- Unstable systemic disease as judged by the investigator: including but not limited to severe liver, kidney or metabolic disease requiring drug therapy
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- Presence of chronic progressive neurological disease
- Patients who have not recovered from acute toxic effects of prior treatment
- Active or uncontrolled infection requiring systemic treatment (except mild urogenital and upper respiratory tract infections)
- Pregnancy-capable female subjects who plan to become pregnant within 2 years of cell reinfusion; or male subjects whose partners plan to become pregnant within 2 years of cell reinfusion
- Those who have received CAR-T therapy or other gene-modified cell therapy before screening
- Participated in other clinical studies within 1 month before screening
- Subjects screened for evidence of central nervous system involvement
- For patients with liver metastases, the distribution of liver metastases exceeds 1/2 of the liver
- According to the judgment of the investigators, it does not meet the situation of cell preparation
- Other circumstances deemed inappropriate by investigators
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China2 sites, 2 recruiting
- Not yet recruiting
Shandong Cancer Hospital and Institute
Jinan, Shandong, 250000
Jingfu Wang, Doctor, 86-13821271562, wangjingfu666@163.com
Jingfu Wang, Doctor
- Recruiting
Tianjin Medical University Cancer Institute and Hospital
Tianjin, Tianjin Municipality, 300000
Qiang Zhao, Doctor, 86-18622221005, qiangzhao169@aliyun.com
Qiang Zhao, Doctor
About this study
Official title: An Open-label, Dose-escalation, and Dose-expansion Phase I Trial of TAA06 Injection in Patients With Relapsed/Refractory Neuroblastoma
Phase I clinical trials are designed as open-label, dose-escalation and dose-expansion clinical studies, the main purpose of which is to explore the tolerability, safety, cytokinetic characteristics and RP2D and preliminary observation of the efficacy of the study drug in subjects with B7-H3-positive relapsed/refractory neuroblastoma.
Read the detailed description
In the dose-escalation phase of the Phase I clinical trial, a traditional 3+3 trial design was adopted, with a total of 3 dose groups designed. The dose of T/kg was gradually increased, and a total of 12-18 subjects with relapsed/refractory neuroblastoma were enrolled.Within each dose group, the next subject can be dosed after the previous subject has completed at least 14 days of safety observations. After the last subject of each dose group completed the dose-limited toxicity (DLT) evaluation within 28 days after a single dose, the SMC (Safety Monitoring Committee) agreed to enter the next dose group after evaluating the clinical safety data. After that, the enrolment treatment for the next dose group can be started.When 1 DLT occurs in 3 subjects in a dose group, 3 additional subjects in the same dose group (up to 6 subjects in this dose group complete the DLT assessment): If the additional 3 subjects If no DLT occurs, continue dose escalation; if 1 out of 3 additional subjects develops DLT, stop dose escalation; if \> 1 of 3 additional subjects develops DLT DLT, then stop the dose escalation, and at the same time need to reduce a dose to continue to enroll 3 subjects for DLT evaluation.
In the dose expansion phase of the Phase I clinical trial, SMC will review the obtained safety and available data on efficacy, PK, immunogenicity, etc., and give the RP2D dose after comprehensive evaluation. In the dose expansion phase, the RP2D dose group will continue to be enrolled 3 ~6 subjects, further clarify the preliminary efficacy and safety of RP2D.
- Being tested
- T cell injection targeting B7-H3 chimeric antigen receptor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
T cell injection targeting B7-H3 chimeric antigen receptorBiological
Also called TAA06 Injection
The subjects will be administered once.
| Study group | Role | What they receive |
|---|---|---|
| T cell injection targeting TAA06 chimeric antigen receptor | Experimental | The subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 2.0 × 10^6, 4.0 × 10^6 and 8.0 × 10^6 CAR-T/kg groups in order of sequence. Receives: Biological: T cell injection targeting B7-H3 chimeric antigen receptor |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD
Maximum tolerated dose of TAA06 Injection in subjects with relapsed/refractory neuroblastoma
Measured: about 3 years
RP2D
Phase 2 recommended dose of TAA06 Injection in subjects with relapsed/refractory
Measured: about 3 years
Assessment of the safety after B7-H3-targeted chimeric antigen receptor T cells infusion (Safety)
Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) ,(according to the evaluation criteria for common adverse events, NCICTCAE version 5.0)
Measured: about 3 years
Secondary outcomes (10)
Assessment of pharmacokinetic (about Cmax)
Assessment of the highest concentration (Cmax) of B7-H3-targeted chimeric antigen receptor T cells amplified in peripheral blood after administration.
Measured: about 3 years
Assessment of pharmacokinetic (about Tmax)
Assessment of the time to reach the highest concentration (Tmax) of B7-H3-targeted chimeric antigen receptor T cells amplified in peripheral blood after administration.
Measured: about 3 years
Assessment of pharmacokinetic (about AUC0-28d)
Assessment of the area under the curve AUC0-28d after administration.
Measured: about 3 years
Assessment of pharmacokinetic (about AUC0-90d)
Assessment of the area under the curve AUC0-90d after administration.
Measured: about 3 years
Objective Response Rate (ORR)
The proportion of patients whose tumors have shrunk to a certain amount and maintained for a certain period of time , including Complete Response (CR) and Partial Response (PR) cases.（According to the evaluation standard of solid tumor effect (RECISTv1.1)）
Measured: about 3 years
Disease Control Rate（DCR）
The proportion of patients whose tumors have shrunk or remained stable for a certain period of time , including Complete Response (CR), Partial Response (PR) and Stable Disease (SD) cases.（According to the evaluation standard of solid tumor effect (RECISTv1.1)）
Measured: about 3 years
Duration of Response（DOR）
The time from the first evaluation of CR or PR to the time of death of PD (ProgressiveDisease) or any cause.（According to the evaluation standard of solid tumor effect (RECISTv1.1)）
Measured: about 3 years
Progression-free Survival（PFS）
The time from start of B7-H3 CAR-T cell therapy to the first occurrence of disease progression or death of any cause.（According to the evaluation standard of solid tumor effect (RECISTv1.1)）
Measured: about 3 years
To Evaluate Anti-tumour Activity (Overall Survival)
Defined as the time from start of B7-H3 CAR-T cell therapy to death (due to any cause)
Measured: about 3 years
Immunogenicity endpoints
Positive rate of human anti-CAR antibody at each time point.
Measured: about 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2022
- Study start30 Dec 2022
- Primary completion18 Dec 2025 (estimated)
- Study completion18 Feb 2039 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B7-H3-positive Relapsed/ Refractory NeuroblastomaStudies of the same condition, open and under way.
- More trials run by PersonGen BioTherapeutics (Suzhou) Co., Ltd.The sponsor's other registered studies.
- 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
- Model description
- Single group of qualified subjects used TAA06 injection
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- PersonGen BioTherapeutics (Suzhou) Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Tianjin Medical University Cancer Institute and Hospital, Shandong Cancer Hospital and Institute
- Responsible party
- Sponsor
- Investigators
- Qiang Zhao, Doctor, Principal investigator, Tianjin Medical University Cancer Institute and HospitalJingfu Wang, Doctor, Principal investigator, Shandong Cancer Hospital and Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05562024
- Sponsor's protocol ID
- PG-CART-TAA06-001(1)
- Status last verified
- Feb 2023
- First submitted
- 23 Sep 2022
- Last updated
- 27 Feb 2023
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Dose-escalation, and Dose-expansion Phase I Trial of TAA06 Injection in Patients With Relapsed/Refractory Neuroblastoma
- ClinicalTrials.gov ID
- NCT05562024
- Acronym / sponsor ID
- PG-CART-TAA06-001(1)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- PersonGen BioTherapeutics (Suzhou) Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Tianjin Medical University Cancer Institute and Hospital, Shandong Cancer Hospital and Institute
- Study start
- 30 Dec 2022 (actual)
- Primary completion
- 18 Dec 2025 (estimated)
- Study completion
- 18 Feb 2039 (estimated)
- First posted
- 30 Sep 2022 (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 I clinical trials are designed as open-label, dose-escalation and dose-expansion clinical studies, the main purpose of which is to explore the tolerability, safety, cytokinetic characteristics and RP2D and preliminary observation of the efficacy of the study drug in subjects with B7-H3-positive relapsed/refractory neuroblastoma.
Detailed description
In the dose-escalation phase of the Phase I clinical trial, a traditional 3+3 trial design was adopted, with a total of 3 dose groups designed. The dose of T/kg was gradually increased, and a total of 12-18 subjects with relapsed/refractory neuroblastoma were enrolled.Within each dose group, the next subject can be dosed after the previous subject has completed at least 14 days of safety observations. After the last subject of each dose group completed the dose-limited toxicity (DLT) evaluation within 28 days after a single dose, the SMC (Safety Monitoring Committee) agreed to enter the next dose group after evaluating the clinical safety data. After that, the enrolment treatment for the next dose group can be started.When 1 DLT occurs in 3 subjects in a dose group, 3 additional subjects in the same dose group (up to 6 subjects in this dose group complete the DLT assessment): If the additional 3 subjects If no DLT occurs, continue dose escalation; if 1 out of 3 additional subjects develops DLT, stop dose escalation; if \> 1 of 3 additional subjects develops DLT DLT, then stop the dose escalation, and at the same time need to reduce a dose to continue to enroll 3 subjects for DLT evaluation.
In the dose expansion phase of the Phase I clinical trial, SMC will review the obtained safety and available data on efficacy, PK, immunogenicity, etc., and give the RP2D dose after comprehensive evaluation. In the dose expansion phase, the RP2D dose group will continue to be enrolled 3 ~6 subjects, further clarify the preliminary efficacy and safety of RP2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single group of qualified subjects used TAA06 injection
| Arm | Type | Receives |
|---|---|---|
| T cell injection targeting TAA06 chimeric antigen receptor | Experimental | Biological: T cell injection targeting B7-H3 chimeric antigen receptorThe subjects, who sign the informed consent forms and been screened by inclusion/exclusion criteria, will be assigned into 2.0 × 10^6, 4.0 × 10^6 and 8.0 × 10^6 CAR-T/kg groups in order of sequence. |
Who may qualify
- Ages
- 1 year and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (15 listed)
- Age ≥ 1 year (including cut-off value), gender is not limited
- Expected survival time ≥ 3 months
- Karnofsky score (> 16 years) or Lansky score (≤ 16 years) > 60 points
- Meet the clinical diagnostic criteria and be diagnosed as recurrent / refractory neuroblastoma. For first-line standard treatment, please refer to the consensus of experts in the diagnosis and treatment of Pediatric Neuroblastoma (Chinese Journal of Pediatric surgery, Volume 36, No. 1, 2015), the guidelines for the diagnosis and treatment of Pediatric Neuroblastoma of 2019 by the Health Commission, and the consensus of experts in the diagnosis and treatment of Pediatric Neuroblastoma (CCCG-NB-2021 Program) (Chinese Journal of Pediatric surgery, Volume 43, No. 7, 2022)
- The tumor tissue samples of the subjects were stained by immunohistochemistry (IHC) to show that the expression intensity of B7-H3 on the surface of tumor cell membranes was 1+ or above, and the proportion of positive staining of tumor cell membranes was ≥1%
Key exclusion criteria (16 listed)
- Patients who were judged by the investigator to require long-term immunosuppressive therapy at the time of screening
- Cerebrovascular accident or seizure occurred within 6 months before signing the informed consent
- Malignant tumors other than neuroblastoma, excluding carcinoma in situ
- Hepatitis B surface antigen (HBsAg) positive; hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection not within the normal reference range; hepatitis C virus (HCV) antibody positive and peripheral blood type C Hepatitis virus (HCV) RNA positive; human immunodeficiency virus (HIV) antibody positive; cytomegalovirus (CMV) DNA positive; syphilis positive
- Serious cardiac disease: including but not limited to unstable angina, myocardial infarction (within 6 months prior to screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade III), severe arrhythmia
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 |
|---|---|---|
| T cell injection targeting B7-H3 chimeric antigen receptorAlso: TAA06 InjectionThe subjects will be administered once. | Biological | T cell injection targeting TAA06 chimeric antigen receptor |
Primary outcome
MTD
Time frame: about 3 years
Maximum tolerated dose of TAA06 Injection in subjects with relapsed/refractory neuroblastoma
RP2D
Time frame: about 3 years
Phase 2 recommended dose of TAA06 Injection in subjects with relapsed/refractory
Assessment of the safety after B7-H3-targeted chimeric antigen receptor T cells infusion (Safety)
Time frame: about 3 years
Treatment Emergent Adverse Events (TEAE) and Serious Adverse Events (SAE) ,(according to the evaluation criteria for common adverse events, NCICTCAE version 5.0)
10 secondary outcomes
Assessment of pharmacokinetic (about Cmax)
Time frame: about 3 years
Assessment of pharmacokinetic (about Tmax)
Time frame: about 3 years
Assessment of pharmacokinetic (about AUC0-28d)
Time frame: about 3 years
Assessment of pharmacokinetic (about AUC0-90d)
Time frame: about 3 years
Objective Response Rate (ORR)
Time frame: about 3 years
Disease Control Rate（DCR）
Time frame: about 3 years
Duration of Response（DOR）
Time frame: about 3 years
Progression-free Survival（PFS）
Time frame: about 3 years
To Evaluate Anti-tumour Activity (Overall Survival)
Time frame: about 3 years
Immunogenicity endpoints
Time frame: about 3 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2023.
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.
Qiang Zhao, Doctor principal investigator
Tianjin Medical University Cancer Institute and Hospital
Jingfu Wang, Doctor principal investigator
Shandong Cancer Hospital and Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing T cell injection targeting B7-H3 chimeric antigen receptor in people with B7-H3-positive Relapsed/ Refractory Neuroblastoma, run by PersonGen BioTherapeutics (Suzhou) Co., Ltd. at 2 sites 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 15 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 27 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact HuiMin Meng, Doctor (86-18015580390, huimin.meng@persongen.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MTD (time frame: about 3 years). 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 27 Feb 2023.