Solid TumorEarly Phase 1NCT05166070
An Exploratory Clinical Study of RD133 in Subjects With Relapsed or Refractory MSLN-Positive Solid Tumors
A Early Phase 1 study testing RD133 in people with Solid Tumor, run by The First Affiliated Hospital with Nanjing Medical University at 1 site in China.
Trial summary
This study is a single-center exploratory clinical trial. It is estimated that 9-24 subjects will be enrolled. The "3+3" dose escalation design is adopted. The main purpose is to evaluate the safety of RD133 in the treatment of subjects with relapsed or refractory MSLN-positive solid tumors and explore the Recommend… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor
- What is being tested?
- RD133
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteChina
- Study dates
- 1 Jan 2022to 1 Jan 2037
- Phase
- Early 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The subject must personally sign the written informed consent form approved by the ethics committee before the start of the study;
- ≥18 years of age;
- Have received at least 2 prior standard treatments, and achieved no response to the last-line treatment;
- >25% Mesothelin positive rate on tumor cell membrane confirmed by prior immunohistochemistry of tumor tissue or freshly punctured tissue;
- Expected survival ≥ 12 weeks;
- ECOG score ≤ 2;
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- At least one measurable target lesion that meets the RECIST v1.1 standard;
- Female or male subjects with fertility should agree to practice an effective method of contraception from the day of signing the ICF until 365 days after the infusion. Effective method of contraception is defined as: abstinence or contraceptive methods with an annual failure rate of <1% specified in the plan. ；
- Before being enrolled in the group, the subject must have proper organ function and meet all of the following criteria:
- 9.1 The absolute value of neutrophils≥1.0×10^9/L (granulocyte colony stimulating factor (G-CSF) support is allowed, but must be without supportive treatment within 7 days before the examination); 9.2 Platelet count ≥75×10^9/L (must be without blood transfusion support [including blood component transfusion] or thrombopoietin [TPO], or other treatments for the purpose of increasing platelets within 7 days before the examination); 9.3 Hemoglobin ≥9 g/dl (must be without blood transfusion support [including blood component transfusion] within 7 days before the examination); 9.4 Bilirubin value ≤1.5×upper limit of normal (ULN) (except bile duct obstruction caused by tumor compression); 9.5 Creatinine clearance rate ≥60 ml/min; 9.6 ALT or AST ≤2.5×upper limit of normal (ULN) (with liver involvement ≤5×ULN); 9.7 The results of echocardiography indicate that the cardiac ejection fraction is ≥ 50%, without obvious pericardial effusion; 9.8 Stable coagulation function: INR ≤ 1.5, APTT ≤1.2×ULN (except tumor-related anticoagulation therapy); 9.9 >91% basic blood oxygen saturation in the natural indoor air environments.
Who cannot join
- Subject who has received any of the following prior treatments:
- 1.1 Subject with acute or chronic graft-versus-host disease (GVHD) who need systemic treatment within 4 weeks before enrollment; 1.2 Subject who has received gene therapy before enrollment; 1.3 Subject who needs systematic immunosuppressive therapy (except topical drugs) to control autoimmune diseases (eg: Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.), immunodeficiency or other diseases in the first 2 years after enrollment; 1.4 Subject who has been injected with live vaccines within 4 weeks before enrollment; 1.5 Subject has received other interventional clinical research drugs within 12 weeks before apheresis.
- Subject with central metastasis or complete intestinal obstruction;
- Subject with moderate or more severe hydrothorax and ascites which are hard to control by conventional treatment and require continuous catheter drainage;
- With an active malignant tumor in the past 5 years, unless it is a curable tumor and has been obviously cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc.
- Subject with positive hepatitis B surface antigen (HBsAg) or hepatitis B core antibody (HBcAb) and abnormal HBV DNA test results in peripheral blood (abnormal HBV DNA test results are defined as: HBV DNA quantitative level higher than the lower limit of the detection center or higher than normal range of the detection center; or qualitative HBV DNA test positive); Hepatitis C virus (HCV) antibody positive and peripheral blood hepatitis C virus (HCV) RNA positive; Human immunodeficiency virus (HIV) antibody positive; Cytomegalovirus ( CMV) DNA test positive; syphilis test RPR positive.
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- With an uncontrollable active infection (except genitourinary system infection and upper respiratory tract infection <CTCAE Grade 2).
- Severe heart disease: including but not limited to unstable angina, myocardial infarction (within 6 months before screening), congestive heart failure (New York Heart Association [NYHA] classification ≥ grade 3), severe arrhythmia.
- Subject with hypertension that cannot be controlled by medication.
- The toxicity of previous treatment has not been relieved to baseline or ≤1 (NCI-CTCAE v5.0, except for hair loss and laboratory abnormalities without clinical significance).
- Major surgery within 2 weeks before enrollment, or has surgery planned during the time the subject is expected to be infused with RD133 or within 12 weeks after RD133 infusion (except planned surgery under local anesthesia).
- Subject who has a solid organ transplant.
- Women who are pregnant or breastfeeding.
- Subject with previous central nervous system diseases (such as cerebral aneurysm, epilepsy, stroke, Alzheimer's disease, mental illness, etc.) or mental disorders.
- Other unstable systemic diseases judged by the investigator: including but not limited to severe liver, kidney, or metabolic diseases that require medication.
- Known to have life-threatening allergic reactions, hypersensitivity reactions or intolerances to RD133 cell preparations or its components.
- Subject with hemorrhage, severe thrombosis judged by the Investigator, or hereditary/acquired hemorrhage and severe thrombosis (including hemophilia, coagulopathy, thrombocytopenia, hypersplenism, etc.), or are receiving thrombolytic or anticoagulant.
- The researcher believes that other situations are not suitable for inclusion in the group.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Lingxiang Liu contact
China1 site, 1 recruiting
- Recruiting
The First Affiliated Hospital with Nanjing Medical University
Nanjing, Jiangsu, 210029
Lingxiang Liu, llxlau@163.com
About this study
Official title: An Exploratory Clinical Study to Evaluate the Safety and Efficacy of RD133 in Subjects With Relapsed or Refractory MSLN-Positive Solid Tumors
This study is a single-center exploratory clinical trial. It is estimated that 9-24 subjects will be enrolled. The "3+3" dose escalation design is adopted. The main purpose is to evaluate the safety of RD133 in the treatment of subjects with relapsed or refractory MSLN-positive solid tumors and explore the Recommend phase II dose of RD133 in the treatment of patients with relapsed/refractory MSLN-positive solid tumors.
Read the detailed description
Leukapheresis procedure will be performed to manufacture RD133 chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of RD133 at 1.0, 3.0, or 6.0x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after RD133 infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after RD133 infusion.
- Conditions
- Solid Tumor
- Being tested
- RD133
- Keywords
- mesothelin-positive solid tumor, CAR-T
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RD133Drug
The enhanced MSLN-CAR-T cell design of this study is obtained by co-infecting T cells with two lentiviral vectors. One lentiviral vector expresses CD19-CAR and tEGFR molecular safety switch, and the other lentiviral vector expresses MSLN- CAR and dnTGFβRII receptors. dnTGFβRII receptor without intracellular signal is used to resist the inhibition of T cell function by the immune microenvironment of tumor tissue. In addition, for the safety of CAR-T cell application in vivo, tEGFR is used in the CAR design as a molecular safety switch for CAR-T cells.
| Study group | Role | What they receive |
|---|---|---|
| Administration of RD133 | Experimental | Three dose groups of 1.0×10^6 CAR-T/kg, 3.0×10^6 CAR-T/kg, and 6.0×10^6 CAR-T/kg RD133 are designed in this study. 3 to 6 subjects are expected to be enrolled in each dose group according to observed DLT.
RD133 will be intravenously infused at least 24 hours after lymphodepletion preconditioning. According to the assigned dose group, the designated dose of RD133 will be infused in a single infusion within 30 minutes on day 0. Receives: Drug: RD133 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Type and incidence of dose-limiting toxicity (DLT) by dose group
The number and percentage of DLT in each dose group
Measured: 2 years post infusion
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity.
Measured: 2 years post infusion
Secondary outcomes (9)
Number of Participants With Adverse Events
An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product
Measured: 2 years post infusion
Objective response rate (ORR)
The proportion of subjects who have achieved best response of partial response (PR) or complete response (CR) according to the RECIST V1.1 evaluation criteria 3 months after RD133 cell infusion.
Measured: 2 years post infusion
Duration of response (DoR)
The time from the date of initial documentation of CR/PR after RD133 cell infusion to the date of progressive disease or death due to the disease studied
Measured: 2 years post infusion
Time to response (TTR)
The time from the date of RD133 cell infusion to the first efficacy evaluation of partial response (PR) or complete response (CR)
Measured: 2 years post infusion
Disease control rate (DCR)
The proportion of subjects with best efficacy assessment of complete response (CR), partial response (PR) or stable disease (SD)
Measured: 2 years post infusion
Progression-free survival (PFS)
The time from the date of RD133 cell infusion to the date of initial documentation of progressive disease/relapse or death from any cause
Measured: 2 years post infusion
Overall survival (OS)
The time from the date of RD133 cell infusion to the date of death
Measured: 2 years post infusion
Transgene Levels of RD133
Changes of virus vector copy number (VCN) in peripheral blood and tumor tissue (if any) after RD133 infusion
Measured: 2 years post infusion
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Changes of CAR T cell concentration in peripheral blood and tumor tissue (if any) after RD133 infusion
Measured: 2 years post infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Dec 2021
- Study start1 Jan 2022 (estimated)
- Primary completion1 Jan 2024 (estimated)
- Study completion1 Jan 2037 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid TumorStudies of the same condition, open and under way.
- More trials run by The First Affiliated Hospital with Nanjing Medical UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study is a single center, open label, non-controlled, exploratory study. The "3+3"dose escalation design will be implemented to evaluate the safety and tolerability of RD133 in the treatment of subjects with relapsed/refractory MSLN-positive solid tumors.
- Masking
- None (open label)
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Shanghai IASO Biotechnology Co., Ltd
- Responsible party
- Principal investigator, Lingxiang Liu, The First Affiliated Hospital with Nanjing Medical University
- Investigators
- Lingxiang Liu, Principal investigator, The First Affiliated Hospital with Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05166070
- Sponsor's protocol ID
- RD133CI002
- Status last verified
- Dec 2021
- First submitted
- 10 Nov 2021
- Last updated
- 21 Dec 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Clinical Study to Evaluate the Safety and Efficacy of RD133 in Subjects With Relapsed or Refractory MSLN-Positive Solid Tumors
- ClinicalTrials.gov ID
- NCT05166070
- Acronym / sponsor ID
- RD133CI002
- Conditions
- Solid Tumor
- Keywords
- mesothelin-positive solid tumor, CAR-T
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The First Affiliated Hospital with Nanjing Medical UniversityUniversity, hospital or other
- Collaborators
- Shanghai IASO Biotechnology Co., Ltd
- Study start
- 1 Jan 2022 (estimated)
- Primary completion
- 1 Jan 2024 (estimated)
- Study completion
- 1 Jan 2037 (estimated)
- First posted
- 21 Dec 2021 (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.
This study is a single-center exploratory clinical trial. It is estimated that 9-24 subjects will be enrolled. The "3+3" dose escalation design is adopted. The main purpose is to evaluate the safety of RD133 in the treatment of subjects with relapsed or refractory MSLN-positive solid tumors and explore the Recommend phase II dose of RD133 in the treatment of patients with relapsed/refractory MSLN-positive solid tumors.
Detailed description
Leukapheresis procedure will be performed to manufacture RD133 chimeric antigen receptor (CAR) modified T cells. Bridging therapy is allowed between PBMC collection and lymphodepletion. Lymphodepletion with fludarabine and cyclophosphamide was performed for three consecutive days. After 1-day rest, subjects will receive a single dose infusion of RD133 at 1.0, 3.0, or 6.0x 10^6 CAR+ T cells/Kg. Subjects will be followed in the study for a minimum of 2 years after RD133 infusion. Long-term follow-up for lentiviral vector safety will be followed for up to 15 years after RD133 infusion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study is a single center, open label, non-controlled, exploratory study. The "3+3"dose escalation design will be implemented to evaluate the safety and tolerability of RD133 in the treatment of subjects with relapsed/refractory MSLN-positive solid tumors.
| Arm | Type | Receives |
|---|---|---|
| Administration of RD133 | Experimental | Drug: RD133Three dose groups of 1.0×10^6 CAR-T/kg, 3.0×10^6 CAR-T/kg, and 6.0×10^6 CAR-T/kg RD133 are designed in this study. 3 to 6 subjects are expected to be enrolled in each dose group according to observed DLT. RD133 will be intravenously infused at least 24 hours after lymphodepletion preconditioning. According to the assigned dose group, the designated dose of RD133 will be infused in a single infusion within 30 minutes on day 0. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- The subject must personally sign the written informed consent form approved by the ethics committee before the start of the study;
- ≥18 years of age;
- Have received at least 2 prior standard treatments, and achieved no response to the last-line treatment;
- >25% Mesothelin positive rate on tumor cell membrane confirmed by prior immunohistochemistry of tumor tissue or freshly punctured tissue;
- Expected survival ≥ 12 weeks;
Key exclusion criteria (18 listed)
- Subject who has received any of the following prior treatments:
- 1.1 Subject with acute or chronic graft-versus-host disease (GVHD) who need systemic treatment within 4 weeks before enrollment; 1.2 Subject who has received gene therapy before enrollment; 1.3 Subject who needs systematic immunosuppressive therapy (except topical drugs) to control autoimmune diseases (eg: Crohn's disease, rheumatoid arthritis, systemic lupus erythematosus, etc.), immunodeficiency or other diseases in the first 2 years after enrollment; 1.4 Subject who has been injected with live vaccines within 4 weeks before enrollment; 1.5 Subject has received other interventional clinical research drugs within 12 weeks before apheresis.
- Subject with central metastasis or complete intestinal obstruction;
- Subject with moderate or more severe hydrothorax and ascites which are hard to control by conventional treatment and require continuous catheter drainage;
- With an active malignant tumor in the past 5 years, unless it is a curable tumor and has been obviously cured, such as basal or squamous cell carcinoma, cervical or breast carcinoma in situ, etc.
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 |
|---|---|---|
| RD133The enhanced MSLN-CAR-T cell design of this study is obtained by co-infecting T cells with two lentiviral vectors. One lentiviral vector expresses CD19-CAR and tEGFR molecular safety switch, and the other lentiviral vector expresses MSLN- CAR and dnTGFβRII receptors. dnTGFβRII receptor without intracellular signal is used to resist the inhibition of T cell function by the immune microenvironment of tumor tissue. In addition, for the safety of CAR-T cell application in vivo, tEGFR is used in the CAR design as a molecular safety switch for CAR-T cells. | Drug | Administration of RD133 |
Primary outcome
Type and incidence of dose-limiting toxicity (DLT) by dose group
Time frame: 2 years post infusion
The number and percentage of DLT in each dose group
Type and incidence of adverse events (AEs) and serious adverse events (SAEs) by dose group
Time frame: 2 years post infusion
Calculate type and incidence of adverse events (AE), serious adverse event (SAE), including those happened after lymphodepletion and after infusion, those related to study drug and lymphodepletion, or those that led to withdrawal from the study. They will also be aggregated by systematic organ classification (SOC), preferred term (PT), and severity.
9 secondary outcomes
Number of Participants With Adverse Events
Time frame: 2 years post infusion
Objective response rate (ORR)
Time frame: 2 years post infusion
Duration of response (DoR)
Time frame: 2 years post infusion
Time to response (TTR)
Time frame: 2 years post infusion
Disease control rate (DCR)
Time frame: 2 years post infusion
Progression-free survival (PFS)
Time frame: 2 years post infusion
Overall survival (OS)
Time frame: 2 years post infusion
Transgene Levels of RD133
Time frame: 2 years post infusion
Chimeric Antigen Receptor T (CAR-T) Positive Cell Concentration
Time frame: 2 years post infusion
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 21 Dec 2021.
- 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.
Lingxiang Liu contact
Lingxiang Liu principal investigator
The First Affiliated Hospital with Nanjing Medical University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing RD133 in people with Solid Tumor, run by The First Affiliated Hospital with Nanjing Medical University 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 10 inclusion and 18 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 21 Dec 2021. 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?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
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 Lingxiang Liu (llxlau@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Type and incidence of dose-limiting toxicity (DLT) by dose group (time frame: 2 years post infusion). 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 21 Dec 2021.