Metastatic TumorPhase 1NCT05468190
A Clinical Research About CD70-positive Advanced/Metastatic Solid Tumors Treated by CD70-targeted CAR-T
A Phase 1 study testing CD70 CAR-T cells in people with Metastatic Tumor and Advanced Solid Tumor, run by Chongqing Precision Biotech Co., Ltd at 1 site in China.
Trial summary
As a phase I clinical research，this study plans to evaluate the safety and tolerability of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic solid tumors, and obtain recommended doses and infusion patterns. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Tumor, Advanced Solid Tumor, Renal Cell Carcinoma
- What is being tested?
- CD70 CAR-T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteChina
- Study dates
- 17 Jul 2022to 17 Jul 2025
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥18 years old, male or female;
- Advanced/metastatic solid tumor confirmed by histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) (positive tumor CD70 expression (tumor CD70 positive (IHC 3+) confirmed by histology or pathology)) ;
- At least after TKI/PARPi, anti-vascular drug treatment is ineffective, there is no available standard treatment plan or standard treatment fails or intolerable (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), There is currently no effective treatment;
- Measurable and evaluable lesions defined by RECIST version 1.1: Measurable disease is defined as at least one lesion that can be accurately measured on at least one level (long diameter needs to be recorded); ), when measured by magnetic resonance imaging (MRI), each lesion must be >10mm, The lymph node must be >15mm in the short axis;
- ECOG 0-2 points (Appendix 2);
- The expected survival time is more than 12 weeks;
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- No serious mental disorder;
- The functions of important organs are basically normal:
- Hematopoietic function: neutrophils 1.0×109/L, platelets 75×109/L, hemoglobin 80g/L;
- Cardiac function: echocardiography showed cardiac ejection fraction ≥50%, and no obvious abnormality was found on electrocardiogram;
- Renal function: serum creatinine≤2.0×ULN;
- Liver function: ALT and AST ≤2.0×ULN (for patients with liver tumor infiltration, it can be relaxed to ≤3.0×ULN);
- Total bilirubin ≤2.0×ULN (Gilbert syndrome or combined liver tumor infiltration can be relaxed to ≤3.0×ULN);
- Oxygen saturation > 92% in non-oxygen state.
- Have apheresis or venous blood collection standards, and have no other contraindications for cell collection;
- Subjects agree to use reliable and effective contraceptive methods for contraception within 1 year after signing the informed consent form to receiving CAR-T cell infusion (excluding rhythm contraception);
- Subjects or their guardians agree to participate in this clinical trial and sign the ICF, indicating that they understand the purpose and procedures of this clinical trial and are willing to participate in the research.
Who cannot join
- Received anti-CD70 drug treatment before screening;
- Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
- Received any of the following treatments before screening:
- Participated in other interventional clinical studies before screening, including: the last use of unmarketed new drugs is less than 3 months before cell reinfusion, or the last use of marketed drugs is less than 5 half-lives from cell reinfusion;
- Received anti-tumor therapy such as chemotherapy and targeted therapy within 2 weeks or at least 5 half-lives (whichever is shorter) before apheresis;
- Received systemic corticosteroid therapy at doses greater than 10 mg/day prednisone (or equivalent doses of other corticosteroids) within 2 weeks prior to apheresis (inhalation or topical allowed in the absence of active autoimmune disease Use steroids and adrenal corticosteroid replacement at doses greater than 10 mg/day of prednisone);
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- Received live attenuated vaccine within 4 weeks before screening;
- Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
- Malignant tumors other than the target tumor within 3 years before screening, except for the following: malignant tumors that have received radical treatment, and no known active disease within ≥ 3 years before enrollment; or Treated non-melanoma skin cancer with no evidence of disease;
- Suffering from any of the following heart diseases:
- New York Heart Association (NYHA) stage III or IV congestive heart failure;
- Myocardial infarction or coronary artery bypass grafting (CABG) within 6 months before enrollment;
- Clinically significant ventricular arrhythmia, or a history of unexplained syncope (except those caused by vasovagal or dehydration);
- History of severe nonischemic cardiomyopathy.
- Known to have active or uncontrolled autoimmune diseases, such as Crohns disease, rheumatoid arthritis, systemic lupus erythematosus, systemic vasculitis, etc.;
- Hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) positive and peripheral blood hepatitis B virus (HBV) DNA titer detection is greater than the normal range; hepatitis C virus (HCV) antibody positive and peripheral blood type C Hepatitis virus (HCV) RNA titer detection greater than normal range Human immunodeficiency virus (HIV) antibody positive; syphilis positive test; cytomegalovirus (CMV) DNA test positive;
- The subject has experienced venous thromboembolic events (for example: pulmonary embolism) and still needs anticoagulation therapy, or meets the following conditions: a. Bleeding with grades 3 to 4 for more than 30 days; b. There are venous Sequelae caused by embolism (such as persistent dyspnea and hypoxia); Arterial embolism but those who do not meet the above conditions can participate in the trial);
- Poorly controlled hypertension, defined as systolic blood pressure ≥150mmHg and/or diastolic blood pressure ≥90mmHg (blood pressure values are measured based on the average of 3 readings at least 2 minutes apart, blood pressure ≥150/90mmHg at initial screening Receive antihypertensive treatment, if the treatment is well controlled and blood pressure is less than 150/90mmHg, screening can be performed);
- Women who are pregnant or breastfeeding, and male or female subjects who plan to have children within 1 year after receiving CAR-T cell reinfusion;
- Other investigators deem it unsuitable to participate in the study.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Henan Cancer Hospital
Zhengzhou, Henan, 450000
Quanli Gao, MD, 15038171966, zlyygql0855@zzu.edu.cn
About this study
Official title: A Phase I Clinical Study to Assess the Safety and Tolerability of CD70-targeting CAR-T in the Treatment of CD70-positive Advanced/Metastatic Solid Tumors
As a phase I clinical research，this study plans to evaluate the safety and tolerability of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic solid tumors, and obtain recommended doses and infusion patterns.
Read the detailed description
This is a single-center, double-arm, open-label study. The research designs to follow 2 groups：Intravenous infusion group and Intraperitoneal injection group；each group sets up 2 phases,the first phase is dose discovery phase to obtain recommended doses,the second phase is dose expansion phase to verify the safety in the recommended doses. In the discovery phase,each group puts up 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.In the dose expansion phase,each group will choose one or two dose groups to verify the safety and efficacy at this dose,and plan to recruit about 6 subjects in each dose group.
- Conditions
- Metastatic Tumor, Advanced Solid Tumor, Renal Cell Carcinoma, Ovarian Cancer, Cervix Cancer
- Being tested
- CD70 CAR-T cells
- Keywords
- CAR-T, CD70, CD70-positive advanced/metastatic solid tumors
- Medical subject headings
- Neoplasm Metastasis, Carcinoma, Renal Cell, Ovarian Neoplasms, Uterine Cervical Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CD70 CAR-T cellsBiological
Administration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
CD70 CAR-T cellsBiological
Administration method: intraperitoneal injection；Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion.
| Study group | Role | What they receive |
|---|---|---|
| Intravenous of CD70-targeted CAR-T | Experimental | Infusion of CD70-targeted CAR-T cells by dose of 1-10x10^6 cells/kg Receives: Biological: CD70 CAR-T cells |
| intraperitoneal injection of CD70-targeted CAR-T | Experimental | Infusion of CD70-targeted CAR-T cells by dose of 1-10x10^6 cells/kg Receives: Biological: CD70 CAR-T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability]
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
Measured: 28 days
Obtain the maximum tolerated dose of CD70 CAR-T cells[Safety and Tolerability]
Dose-limiting toxicity after cell infusion
Measured: 28 days
Secondary outcomes (9)
Disease control rate of CAR-T cell preparations in CD70 positive advanced malignancies [Effectiveness]
Disease control rate: The proportion of subjects who achieved CR, PR, SD after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
Measured: 3 months
Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Objective response rate includes：The proportion of subjects who achieved CR, PR after CAR-T infusion accounted for all treated subjects (Assessed based on RECIST criteria)，the minimum value is 0%，maximum value is 100%, and higher scores mean a better outcome.
Measured: 3 months
Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
DOR will be assessed from the first assessment of CR/PR/SD to the first assessment of recurrence or progression of the disease or death from any cause
Measured: 2 years
Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
PFS will be assessed from the first CD70-CAR-T cell infusion to death from any cause or the first assessment of progression(Assessed based on RECIST criteria)
Measured: 2 years
Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
OS will be assessed from the first CD70-CAR-T cell infusion to death from any cause (Assessed based on RECIST criteria)
Measured: 2 years
AUCS of CD70 CAR-T cells [Cell dynamics]
AUCS is defined as the area under the curve in 90 days
Measured: 3 months
CMAX of CD70 CAR-T cells [Cell dynamics]
CMAX is defined as the highest concentration of CD70 CAR-T cells expanded in peripheral blood
Measured: 3 months
TMAX of CD70 CAR-T cells[Cell dynamics]
TMAX is defined as the time to reach the highest concentration
Measured: 3 months
Pharmacodynamics of CD70 CAR-T cells[Cell dynamics]
Concentration levels of CAR-T-related serum cytokines such as CRP, IL-6, ferritin at each time point，which measured by Chemiluminescence method
Measured: 3 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2022
- Study start17 Jul 2022
- Primary completion17 Jul 2024 (estimated)
- Study completion17 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic TumorStudies of the same condition, open and under way.
- More trials run by Chongqing Precision Biotech Co., LtdThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chongqing Precision Biotech Co., Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Quanli Gao, M.D, Principal investigator, Henan Cancer Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05468190
- Sponsor's protocol ID
- PBC041
- Status last verified
- Aug 2023
- First submitted
- 19 Jul 2022
- Last updated
- 18 Aug 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 18 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Clinical Study to Assess the Safety and Tolerability of CD70-targeting CAR-T in the Treatment of CD70-positive Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT05468190
- Acronym / sponsor ID
- PBC041
- Conditions
- Metastatic Tumor, Advanced Solid Tumor, Renal Cell Carcinoma, Ovarian Cancer, Cervix Cancer
- Keywords
- CAR-T, CD70, CD70-positive advanced/metastatic solid tumors
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Chongqing Precision Biotech Co., LtdIndustry (pharma, biotech, devices)
- Study start
- 17 Jul 2022 (actual)
- Primary completion
- 17 Jul 2024 (estimated)
- Study completion
- 17 Jul 2025 (estimated)
- First posted
- 21 Jul 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.
As a phase I clinical research，this study plans to evaluate the safety and tolerability of CD70-targeting CAR-T cells in the treatment of CD70-positive advanced/metastatic solid tumors, and obtain recommended doses and infusion patterns.
Detailed description
This is a single-center, double-arm, open-label study. The research designs to follow 2 groups：Intravenous infusion group and Intraperitoneal injection group；each group sets up 2 phases,the first phase is dose discovery phase to obtain recommended doses,the second phase is dose expansion phase to verify the safety in the recommended doses. In the discovery phase,each group puts up 4 dose groups, adopting a dose-escalating 3+3 design, and plan to recruit about 12 subjects with CD70-positive advanced/metastatic solid tumors.In the dose expansion phase,each group will choose one or two dose groups to verify the safety and efficacy at this dose,and plan to recruit about 6 subjects in each dose group.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intravenous of CD70-targeted CAR-T | Experimental | Biological: CD70 CAR-T cellsInfusion of CD70-targeted CAR-T cells by dose of 1-10x10^6 cells/kg |
| intraperitoneal injection of CD70-targeted CAR-T | Experimental | Biological: CD70 CAR-T cellsInfusion of CD70-targeted CAR-T cells by dose of 1-10x10^6 cells/kg |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Age ≥18 years old, male or female;
- Advanced/metastatic solid tumor confirmed by histopathology or cytology (paraffin section or fresh biopsy tumor tissue specimen) (positive tumor CD70 expression (tumor CD70 positive (IHC 3+) confirmed by histology or pathology)) ;
- At least after TKI/PARPi, anti-vascular drug treatment is ineffective, there is no available standard treatment plan or standard treatment fails or intolerable (disease progression or intolerance such as surgery, chemotherapy, radiotherapy, targeted therapy, etc.), There is currently no effective treatment;
- Measurable and evaluable lesions defined by RECIST version 1.1: Measurable disease is defined as at least one lesion that can be accurately measured on at least one level (long diameter needs to be recorded); ), when measured by magnetic resonance imaging (MRI), each lesion must be >10mm, The lymph node must be >15mm in the short axis;
- ECOG 0-2 points (Appendix 2);
Key exclusion criteria (20 listed)
- Received anti-CD70 drug treatment before screening;
- Active/symptomatic central nervous system metastases or meningeal metastases at the time of screening; subjects with brain metastases who have been treated must be confirmed to have no imaging evidence of progression ≥ 4 weeks after the end of treatment before they can be enrolled;
- Received any of the following treatments before screening:
- Active infection or uncontrollable infection requiring systemic treatment within 1 week before screening;
- Malignant tumors other than the target tumor within 3 years before screening, except for the following: malignant tumors that have received radical treatment, and no known active disease within ≥ 3 years before enrollment; or Treated non-melanoma skin cancer with no evidence of disease;
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 |
|---|---|---|
| CD70 CAR-T cellsAdministration method: intravenous infusion； Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion. | Biological | Intravenous of CD70-targeted CAR-T |
| CD70 CAR-T cellsAdministration method: intraperitoneal injection；Subjects will receive conditioning therapy by Fludarabine and Cyclophosphamide before cell infusion. | Biological | intraperitoneal injection of CD70-targeted CAR-T |
Primary outcome
Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability]
Time frame: 28 days
Therapy-related adverse events were recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0)
Obtain the maximum tolerated dose of CD70 CAR-T cells[Safety and Tolerability]
Time frame: 28 days
Dose-limiting toxicity after cell infusion
9 secondary outcomes
Disease control rate of CAR-T cell preparations in CD70 positive advanced malignancies [Effectiveness]
Time frame: 3 months
Objective response rate (ORR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Time frame: 3 months
Duration of Response (DOR) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Time frame: 2 years
Progress-free survival(PFS) of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Time frame: 2 years
Overall survival(OS)of CD70 CAR-T treatment in patients with CD70-positive advanced malignancies[Effectiveness]
Time frame: 2 years
AUCS of CD70 CAR-T cells [Cell dynamics]
Time frame: 3 months
CMAX of CD70 CAR-T cells [Cell dynamics]
Time frame: 3 months
TMAX of CD70 CAR-T cells[Cell dynamics]
Time frame: 3 months
Pharmacodynamics of CD70 CAR-T cells[Cell dynamics]
Time frame: 3 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Aug 2023.
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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.
Quanli Gao, M.D principal investigator
Henan Cancer Hospital
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 CD70 CAR-T cells in people with Metastatic Tumor and Advanced Solid Tumor, run by Chongqing Precision Biotech Co., 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 17 inclusion and 20 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: status not confirmed, as of the sponsor's last update on 18 Aug 2023. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Quanli Gao, M.D (15038171966, zlyygql0855@zzu.edu.cn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of Adverse events after CD70 CAR-T cells infusion [Safety and Tolerability] (time frame: 28 days). The study lists 2 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 18 Aug 2023.