Colorectal CancerEarly Phase 1NCT04503980
αPD1-MSLN-CAR T Cells for the Treatment of MSLN-positive Advanced Solid Tumors
A Early Phase 1 study testing αPD1-MSLN-CAR T cells in people with Colorectal Cancer and Ovarian Cancer, run by Shanghai Cell Therapy Group Co.,Ltd at 1 site in China.
Trial summary
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Colorectal Cancer, Ovarian Cancer
- What is being tested?
- αPD1-MSLN-CAR T cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteChina
- Study dates
- 26 Mar 2020to Jun 2022
- Phase
- Early 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have a histological or cytological diagnosis of advanced solid tumors, such as ovarian cancer，Cholangiocarcinoma，colorectal cancer;
- Patients must have failed established standard medical anti-cancer therapies；
- Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
- Life expectancy >3 months；
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
- Subjects must meet blood coagulation parameters and have adequate venous peripheral access for apheresis. Patients must also have adequate mononuclear cells for CAR T cell manufacturing；
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- Staining of MSLN must be greater than 50% of the cells in the tumor tissue and with apparent expression in the membrane. PD-L1 expression must be positive. Tissue obtained for the biopsy must be ≤1 year prior to enrollment for screening, not have been previously irradiated or exposed to chemotherapy. If unavailable, new tissue material from a recently obtained surgical or diagnostic biopsy is mandatory for this trial；
- Satisfactory organ and bone marrow function as defined by the following:
- Adequate bone marrow function in the opinion of the Investigator for lymphocyte-depleting chemotherapy: absolute neutrophil count must be greater than ≥ 1.5×109/L, lymphocyte count must be greater than ≥ 0.5×109/L, platelets must be greater than ≥ 90×109/L, hemoglobin must be greater than ≥ 90g/L without transfusion within 7 days or dependency on EPO;
- Total bilirubin must be less than or equal to two times (≤2.0x) the institutional normal upper limit; transaminases, serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST), must be less than or equal to 2.5 times (≤2.5x) the institutional normal upper limit (≤2.5x if there is hepatic metastasis);
- Creatinine must be less than or equal to one and one half times (≤ 1.5x) the institutional normal upper limit or eGFR ≥ 60ml/min/1.73m^2 [eGFR=186×（age）-0.203×SCr-1.154（mg/dl）,for female the eGFR shoud be timed by 0.742];
- International normalized ratio (INR) or the PT is not greater than one and one half times (≤ 1.5) the upper limit of normal;
- Lung function: ≤ CTCAE grade 1 dyspnea and SaO2≥ 91%
- Cardiac function: cardiac ejection fraction (LVEF) must be greater than fifty percent (≥50%) by echocardiogram or MUGA one month before enrollment.
- Subjects must have measureable disease as defined by RECIST 1.1 criteria;
- Subjects sufficiently understand the trial and willingly sign the informed consent;
- For concurrent medication:
- Systemic therapeutic corticosteroids must be stopped 72 hours before CAR-T infusion. However, patients using physiologic replacement doses of corticosteroids, or its equivalent, will be considered eligible;
- Immunosuppressive therapy must be stopped within four (4) weeks prior to enrollment;
- Male and Female subjects agree to use approved contraceptive methods (e.g. birth control pills, barrier device, intrauterine device, abstinence) during the study and for at least 12 months following the last dose of the study cell infusion and until no CAR-T cells can be detected after two consecutive PCR tests.
Who cannot join
- Prior therapy with targeted therapy or cell therapy against MSLN；
- Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad；
- Active bacteria, viral or fungal infection, and not contained after anti-infective therapy (positive results in the blood ≤72 hours before infusion);
- Patient is positive for Syphilis, Human Immunodeficiency Virus (HIV) , active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected);
- Patient has a medical condition such as autoimmune disease or organ transplantation that requires chronic systemic steroid therapy or requires any other form of immunosuppressive medication;
- History of severe cardiac or pulmonary disease, including hypertension that cannot be controlled by medication, and any of the conditions occurred within the past 6 months: congestive heart failure (New York Heart Association functional classification ≥3), cardiac angioplasty and stents, myocardial infarction, unstable angina, or other clinically significant heart disease；
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- Detectable clinically relevant central nervous system (CNS) metastases and/or pathology such as epilepsy/seizure, brain Ischemia/ hemorrhage, dementia, cerebellar disease, or autoimmune disease affecting central nervous system；
- Patient has a history or current evidence of any condition such as neurotic, psychiatric, immune, metabolic and infectious disease, on any therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating Investigator；
- Patient has a known history of a hematologic malignancy, or of another malignant primary solid tumor concurrently, with the exception of :
- Patients with in situ cervical cancer or breast cancer with no evidence of disease for ≥ 3 years after curative treatments;
- Patients who underwent successful definitive resection of in situ cancer with no evidence of disease for ≥5 years;
- Has had chemotherapy, radioactive, small molecules, biological cancer therapy, immunotherapy or other investigational drugs within 4 weeks prior to the initiation of the study；
- Pregnant or breastfeeding women;
- Investigators think that patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study and cooperation with the requirements of the trial, uncontrolled medical, psychological, familial, sociological, or geographical conditions, or is not in the best interest of the patient to participate.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Shanghai Tenth people's Hospital
Shanghai, Shanghai Municipality
Juemin Fang, 021-66302521, 435254611@qq.com
About this study
Official title: An Exploratory Study of αPD1-MSLN-CAR T Cells Secreting PD-1 Nanobodies for the Treatment of MSLN-positive Advanced Solid Tumors
This is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.
- Conditions
- Colorectal Cancer, Ovarian Cancer
- Being tested
- αPD1-MSLN-CAR T cells
- Keywords
- Solid tumors, CAR T cell
- Medical subject headings
- Colorectal Neoplasms, Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
αPD1-MSLN-CAR T cellsBiological
Subjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of αPD1-MSLN-CAR T cells. During αPD1-MSLN-CAR T cells production, subjects will receive cyclophosphamide for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with αPD1-MSLN-CAR T cells by intravenous (IV) injection. The initial dose of 1×10^5 CAR+ T cells/kg will be infused on day 0.
| Study group | Role | What they receive |
|---|---|---|
| CAR T cells therapy | Experimental | The safety and efficacy of αPD1-MSLN-CAR T cells will be assessed in a standard 3+3 dose escalation approach. Four doses of CAR T cells will be evaluated in this study: 1×10^5 CAR+ T cells/kg, 3×10^5 CAR+ T cells/kg, 1×10^6 CAR+ T cells/kg, and 3×10^6 CAR+ T cells/kg. Receives: Biological: αPD1-MSLN-CAR T cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity （DLT）
Safety
Measured: After 28 days of single infusion
Secondary outcomes (6)
Maximum tolerated dose (MTD)
Tolerability
Measured: After 28 days of single infusion
Objective response rate (ORR)
Clinical response will be assessed by RECIST 1.1.
Measured: Month 12
Progression-free survival (PFS)
PFS of patients receiving αPD1-MSLN-CAR T cells
Measured: Month 12
Overall survival (OS)
OS of patients receiving αPD1-MSLN-CAR T cells.
Measured: Month 12
Peak Plasma Concentration (Cmax)
Pharmacokinetics (PK)
Measured: Month 12
Pharmacodynamics (PD)
PD of IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IFN-γ, TNF-α and MCP1 will be analysed after CAR T cell infusion
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Aug 2020
- Study start26 Mar 2020
- Primary completionMar 2021 (estimated)
- Study completionJun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Colorectal CancerStudies 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Cell Therapy Group Co.,Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Shanghai 10th People's Hospital
- Responsible party
- Sponsor
- Investigators
- Qing Qu, Principal investigator, Shanghai 10th People's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04503980
- Sponsor's protocol ID
- BZDS1901
- Status last verified
- Aug 2020
- First submitted
- 5 Aug 2020
- Last updated
- 7 Aug 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of αPD1-MSLN-CAR T Cells Secreting PD-1 Nanobodies for the Treatment of MSLN-positive Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT04503980
- Acronym / sponsor ID
- BZDS1901
- Conditions
- Colorectal Cancer, Ovarian Cancer
- Keywords
- Solid tumors, CAR T cell
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Shanghai Cell Therapy Group Co.,LtdIndustry (pharma, biotech, devices)
- Collaborators
- Shanghai 10th People's Hospital
- Study start
- 26 Mar 2020 (actual)
- Primary completion
- Mar 2021 (estimated)
- Study completion
- Jun 2022 (estimated)
- First posted
- 7 Aug 2020 (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 is a single arm, open-label, dose escalation clinical study to evaluate the safety and tolerability of autologous mesothelin (MSLN)-targeted chimeric antigen receptor (MSLN-CAR) T cells secreting PD-1 nanobodies (αPD1-MSLN-CAR T cells) in patients with solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CAR T cells therapy | Experimental | Biological: αPD1-MSLN-CAR T cellsThe safety and efficacy of αPD1-MSLN-CAR T cells will be assessed in a standard 3+3 dose escalation approach. Four doses of CAR T cells will be evaluated in this study: 1×10^5 CAR+ T cells/kg, 3×10^5 CAR+ T cells/kg, 1×10^6 CAR+ T cells/kg, and 3×10^6 CAR+ T cells/kg. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Patients must have a histological or cytological diagnosis of advanced solid tumors, such as ovarian cancer，Cholangiocarcinoma，colorectal cancer;
- Patients must have failed established standard medical anti-cancer therapies；
- Greater than or equal to 18 years of age and less than or equal to 70 years of age on day of signing informed consent；
- Life expectancy >3 months；
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1;
Key exclusion criteria (14 listed)
- Prior therapy with targeted therapy or cell therapy against MSLN；
- Prior therapy with any gene therapy (including CAR-T cell therapy) or any T cell therapy home and abroad；
- Active bacteria, viral or fungal infection, and not contained after anti-infective therapy (positive results in the blood ≤72 hours before infusion);
- Patient is positive for Syphilis, Human Immunodeficiency Virus (HIV) , active Hepatitis B (HBsAg reactive) or Hepatitis C (HCV RNA (qualitative) is detected);
- Patient has a medical condition such as autoimmune disease or organ transplantation that requires chronic systemic steroid therapy or requires any other form of immunosuppressive medication;
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 |
|---|---|---|
| αPD1-MSLN-CAR T cellsSubjects will undergo leukapheresis to isolate peripheral blood mononuclear cells (PBMCs) for the production of αPD1-MSLN-CAR T cells. During αPD1-MSLN-CAR T cells production, subjects will receive cyclophosphamide for the purpose of lymphocytes depletion. After lymphodepletion, subjects will receive one dose treatment with αPD1-MSLN-CAR T cells by intravenous (IV) injection. The initial dose of 1×10^5 CAR+ T cells/kg will be infused on day 0. | Biological | CAR T cells therapy |
Primary outcome
Dose-limiting toxicity （DLT）
Time frame: After 28 days of single infusion
Safety
6 secondary outcomes
Maximum tolerated dose (MTD)
Time frame: After 28 days of single infusion
Objective response rate (ORR)
Time frame: Month 12
Progression-free survival (PFS)
Time frame: Month 12
Overall survival (OS)
Time frame: Month 12
Peak Plasma Concentration (Cmax)
Time frame: Month 12
Pharmacodynamics (PD)
Time frame: Day 28
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Aug 2020.
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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.
Qing Qu principal investigator
Shanghai 10th People's Hospital
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 αPD1-MSLN-CAR T cells in people with Colorectal Cancer and Ovarian Cancer, run by Shanghai Cell Therapy Group 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 20 inclusion and 14 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 7 Aug 2020. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Juemin Fang (021-66302521, 435254611@qq.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Dose-limiting toxicity （DLT） (time frame: After 28 days of single infusion). 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 7 Aug 2020.