Solid Tumor, AdultPhase 1NCT04976218
TGFβR-KO CAR-EGFR T Cells in Previously Treated Advanced EGFR-positive Solid Tumors
A Phase 1 study testing TGFβR-KO CAR-EGFR T Cells in people with Solid Tumor, Adult and EGFR Overexpression, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. However, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Solid Tumor, Adult, EGFR Overexpression
- What is being tested?
- TGFβR-KO CAR-EGFR T Cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteChina
- Study dates
- 15 Mar 2022to 31 Dec 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
- Age from 18 to 75 years with estimated life expectancy >3 months.
- Histopathological confirmed advanced solid tumors failed to at least first-line standard treatment. EGFR antigen expression level ≥ 50%.
- Have at least one measurable target lesion.
- Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
- Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
- Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
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- Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
- Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.
- Ability to understand and sign a written informed consent document.
- Women of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, and up to 90 days after the last dose of the drug.
Who cannot join
- Active, known or suspected autoimmune diseases.
- Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- History of severe hypersensitive reactions to other monoclonal antibodies.
- History of allergy or intolerance to study drug components.
- Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results.
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- History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
- Uncontrolled intercurrent illness, including ongoing or active systemic infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia (excluding insignificant sinus bradycardia and sinus tachycardia) or psychiatric illness/social situations and any other illness that would limit compliance with study requirements and jeopardize the safety of the patient.
- History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- Pregnant or breast-feeding. Women of childbearing potential must have a pregnancy test performed within 7 days before the enrollment, and a negative result must be documented.
- Previous or concurrent cancer within 3 years prior to treatment start EXCEPT for curatively treated cervical cancer in situ, non-melanoma skin cancer, superficial bladder tumors [Ta (non-invasive tumor), Tis (carcinoma in situ) and T1 (tumor invades lamina propria)].
- Vaccination within 30 days of study enrollment.
- Active bleeding or known hemorrhagic tendency.
- Subjects with unhealed surgical wounds for more than 30 days.
- Being participating any other trials or withdraw within 4 weeks.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Chinese PLA General Hospital
Beijing, Beijing Municipality, 100853
Weidong Han, Prof., 010-66937463, hanwdrsw@sina.com
kaichao Feng, Ph.D
About this study
Official title: Phase Ⅰ Study of EGFR Targeted TGFβR-KO CAR T Cells in the Treatment of Previously Treated Advanced EGFR-positive Solid Tumors
Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. However, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME. In this study, we construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in previously treated advanced EGFR positive solid tumors.
Read the detailed description
Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. Different from the promising efficacy in leukemia, lymphoma and multiple myeloma, however, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME, which plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity. In this phase Ⅰstudy, we plan to construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in the treatment of previously treated advanced EGFR antigen overexpressing solid tumors.
- Conditions
- Solid Tumor, Adult, EGFR Overexpression
- Being tested
- TGFβR-KO CAR-EGFR T Cells
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TGFβR-KO CAR-EGFR T CellsBiological
Enrolled patients will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. The infused CAR+ T cell dose in phase IA will be started initially at 1-2×10^5/kg, dose 2 will be 1×10^6/kg，and dose 3 will be 1×10^7/kg, if DLT occurs in dose level 3, the following dose will return to 5×10^6/kg. In expansion period, the dose of infused CAR+ T cells will be determined by the recommended cell dose from phase IA.
| Study group | Role | What they receive |
|---|---|---|
| Experimental arm | Experimental | Enrolled patients in this arm will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. Receives: Biological: TGFβR-KO CAR-EGFR T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of subjects occuring treatment related adverse events
Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0
Measured: Up to 24 weeks following the infusion of TGFβR-KO CAR-EGFR T cells.
Secondary outcomes (2)
The percentage of enrolled patients that respond to TGFβR-KO CAR-EGFR T cell therapy.
Overall response rate is defined as the sum of partial responses and complete responses
Measured: Up to 24 weeks following the infusion of TGFβR-KO CAR-EGFR T cells.
The percentage of enrolled patients alive and without progression at 6 months
Progression free survival (PFS) is defined as the time from enrollment to documented disease progression or death. Progression will be defined clinically or on imaging as per immune related response evaluation criteria in solid tumors (irRECIST) definition.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2021
- Study start15 Mar 2022
- Primary completion20 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- More trials run by Chinese PLA General HospitalThe 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
- TGFβR-KO CAR-EGFR T Cells will be administered to eligible patients in a 3+3 dose escalation manner.
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Weidong Han, PhD, Principal investigator, Biotherapeutic Department, Chinese PLA General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04976218
- Sponsor's protocol ID
- CHN-PLAGH-BT-067
- Status last verified
- Nov 2022
- First submitted
- 19 Jul 2021
- Last updated
- 16 Nov 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Nov 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ⅰ Study of EGFR Targeted TGFβR-KO CAR T Cells in the Treatment of Previously Treated Advanced EGFR-positive Solid Tumors
- ClinicalTrials.gov ID
- NCT04976218
- Acronym / sponsor ID
- CHN-PLAGH-BT-067
- Conditions
- Solid Tumor, Adult, EGFR Overexpression
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- 20 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 26 Jul 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.
Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. However, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME. In this study, we construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in previously treated advanced EGFR positive solid tumors.
Detailed description
Chimeric antigen receptor modified T (CART) cell therapy has been identified as a breakthrough therapy in hematologic malignancies. Different from the promising efficacy in leukemia, lymphoma and multiple myeloma, however, CART cell therapy yielded no satisfactory efficacy data in the study of solid tumors. One of major challenges is the complicated immunosuppressive tumor microenvironment (TME) in solid tumors. It has been reported that transforming growth factor-β (TGF-β) is one of the major regulatory factors in the TME, which plays a key role in promoting tumor initiation, metastasis, and suppressing anti-tumor immunity. In this phase Ⅰstudy, we plan to construct CAR-EGFR-TGFβR-KO T cell by knocking out TGF-β receptor Ⅱ through CRISPR/Cas9 in order to study the anti-tumor activities and safety profiles of CAR-EGFR-TGFβR-KO T cell in the treatment of previously treated advanced EGFR antigen overexpressing solid tumors.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- TGFβR-KO CAR-EGFR T Cells will be administered to eligible patients in a 3+3 dose escalation manner.
| Arm | Type | Receives |
|---|---|---|
| Experimental arm | Experimental | Biological: TGFβR-KO CAR-EGFR T CellsEnrolled patients in this arm will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Age from 18 to 75 years with estimated life expectancy >3 months.
- Histopathological confirmed advanced solid tumors failed to at least first-line standard treatment. EGFR antigen expression level ≥ 50%.
- Have at least one measurable target lesion.
- Fresh solid tumor samples or formalin-fixed paraffin embedded tumor archival samples within 6 months are necessary; Fresh tumor samples are preferred. Subjects are willing to accept tumor re-biopsy in the process of this study.
- Previous treatment must be completed for more than 4 weeks prior to the enrollment of this study, and subjects have recovered to <= grade 1 toxicity.
Key exclusion criteria (15 listed)
- Active, known or suspected autoimmune diseases.
- Known brain metastases or active central nervous system (CNS). Subjects with CNS metastases who were treated with radiotherapy for at least 3 months prior to enrollment, have no central nervous symptoms and are off corticosteroids, are eligible for enrollment, but require a brain MRI screening.
- Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- History of severe hypersensitive reactions to other monoclonal antibodies.
- History of allergy or intolerance to study drug components.
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 |
|---|---|---|
| TGFβR-KO CAR-EGFR T CellsEnrolled patients will be administered TGFβR-KO CAR-EGFR T Cells in 3+3 based escalation manner. The infused CAR+ T cell dose in phase IA will be started initially at 1-2×10^5/kg, dose 2 will be 1×10^6/kg，and dose 3 will be 1×10^7/kg, if DLT occurs in dose level 3, the following dose will return to 5×10^6/kg. In expansion period, the dose of infused CAR+ T cells will be determined by the recommended cell dose from phase IA. | Biological | Experimental arm |
Primary outcome
Number of subjects occuring treatment related adverse events
Time frame: Up to 24 weeks following the infusion of TGFβR-KO CAR-EGFR T cells.
Determining the safety profile following the initiation of treatment and grading these toxicities by CTCAE v5.0
2 secondary outcomes
The percentage of enrolled patients that respond to TGFβR-KO CAR-EGFR T cell therapy.
Time frame: Up to 24 weeks following the infusion of TGFβR-KO CAR-EGFR T cells.
The percentage of enrolled patients alive and without progression at 6 months
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Nov 2022.
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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.
Weidong Han, PhD principal investigator
Biotherapeutic Department, Chinese PLA General 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 TGFβR-KO CAR-EGFR T Cells in people with Solid Tumor, Adult and EGFR Overexpression, run by Chinese PLA General Hospital 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 15 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 16 Nov 2022. 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 Weidong Han, PhD (+86-10-66937463, hanwdrsw69@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of subjects occuring treatment related adverse events (time frame: Up to 24 weeks following the infusion of TGFβR-KO CAR-EGFR T cells.). 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 16 Nov 2022.