Advanced or Metastatic Solid TumorsPhase 1/2NCT05693844
Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in Advanced/Metastatic Solid Tumors
A Phase 1/2 study testing Pan-T booster co-expressing MSLN CAR T cell, Albumin-bound paclitaxel and Cyclophosphamide in people with Advanced or Metastatic Solid Tumors, run by Chinese PLA General Hospital at 1 site in China.
Trial summary
In preclinical study, investigators have demonstrated that the newly developed pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Advanced or Metastatic Solid Tumors
- What is being tested?
- Pan-T booster co-expressing MSLN CAR T cell, Albumin-bound paclitaxel and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteChina
- Study dates
- 20 Jan 2023to 31 Dec 2026
- Phase
- Phase 1/2
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. Age from 18 to 75 years with estimated life expectancy >3 months.
- 2. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. Mesothelin antigen expression percentage >＝10%.
- 3. Have at least one measurable target lesion.
- 4. 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 rebiopsy in the process of this study.
- 5. 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.
- 6. Have an Eastern Cooperative Oncology Group performance status (ECOG) of 0 or 2 at the time of enrollment.
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- 7. Have adequate organ function, which should be confirmed within 2 weeks prior to the first dose of study drugs.
- 8. Previous treatment with anti-PD-1/PD-L1 antibodies are allowed.
- 9. Ability to understand and sign a written informed consent document.
- 10. 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
- 1. Active, known or suspected autoimmune diseases.
- 2. 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.
- 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- 4. History of severe hypersensitive reactions to other monoclonal antibodies.
- 5. History of allergy or intolerance to study drug components.
- 6. 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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- 7. History or concurrent condition of interstitial lung disease of any grade or severely impaired pulmonary function.
- 8. 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.
- 9. History of human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome (AIDS).
- 10. 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.
- 11. 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)].
- 12. Vaccination within 30 days of study enrollment.
- 13. Active bleeding or known hemorrhagic tendency.
- 14. Subjects with unhealed surgical wounds for more than 30 days.
- 15. Being participating any other trials or withdraw within 4 weeks.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Kaichao Feng
Beijing, Beijing Municipality, 100853
Kaichao Feng, MD, +861066937231, timothyfkc@126.com
Weidong Han, PhD
About this study
Official title: Phase I/II Study of Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in Advanced/Metastatic Solid Tumors
In preclinical study, investigators have demonstrated that the newly developed pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. In this clinical trial, enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1×10^6 cells/kg based on the basic principle of dose escalation design, in order to evaluate the safety, feasibility, pharmacokinetics/pharmacodynamics, and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo.
Read the detailed description
In this study, investigators have developed a novel CAR T cell system targeting mesothelin (MSLN) antigen, termed as Pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell. Preclinical study demonstrated that this novel pan-T booster co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. In this clinical trial, enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1×10^6 cells/kg based on the basic principle of dose escalation design, in order to evaluate the safety, feasibility, pharmacokinetics/pharmacodynamics, and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo. The level of CAR-T cell expansion and the duration of expansion are important determining factors for subsequent dose escalation infusions (3×10^6 cells/kg and 6×10^6 cells/kg). Repeated infusion, immune checkpoint inhibitor (such as anti-PD1/PD-L1) or local therapy (radiotherapy) are allowed when patients achieve clinical benefit and the level of CAR-T cell expansion declines to low level.
In the 3 patients receiving the first dose treatment, we observed high levels of expansion of both total T cells and CAR T cells in the PB after CAR T cell infusion (CAR T > 300 per microliter, total T cells reaching 10 times the number of CAR T cells), one patient experienced a grade 2 pulmonary toxicity and transient liver dysfunction during the CAR T cell expansion period (infusion 14 days later), transient marked enlargement of the spleen, and required to be treated with glucocorticoids and ruxolitinib to control T cell toxicity. Efficacy monitoring showed that some target lesion clearance or reduction could be achieved within 2-4 weeks after CAR T infusion. Based on these observations, it was concluded that low-dose CAR T infusion (CAR+T cells 1×10^6 cells/kg) could achieve the sufficient level of CAR T cell expansion, and the initially planned CAR T dose escalation was dispensable. Subsequent patients after May 10th, 2024, will all be treated using 1×10^6 cells/kg dose.
- Conditions
- Advanced or Metastatic Solid Tumors
- Being tested
- Pan-T booster co-expressing MSLN CAR T cell, Albumin-bound paclitaxel, Cyclophosphamide, Fludarabine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Pan-T booster co-expressing MSLN CAR T cellBiological
Starting Dose: 1×10^6 cells/kg
Albumin-bound paclitaxelDrug
Administered intravenously at dose of 100-200mg/m2 on day -5
CyclophosphamideDrug
Administered intravenously at a total dose of 15-30mg/kg on day -3 and day -2
FludarabineDrug
Administered intravenously at dose of 30mg/m2/d on day -3 and day -2
| Study group | Role | What they receive |
|---|---|---|
| Pan-T booster co-expressing MSLN CAR T cell | Experimental | Before the infusion of pan-T booster co-expressing MSLN CAR T cells, all enrolled patients need to undergo conditioning chemotherapy consisting of albumin-bound paclitaxel, cyclophosphamide, and fludarabine. Receives: Biological: Pan-T booster co-expressing MSLN CAR T cell; Drug: Albumin-bound paclitaxel; Drug: Cyclophosphamide; Drug: Fludarabine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment related adverse events
Treatment related adverse events are defined as any medical events since the initiation of MSLN targeted CAR T cell therapy . CRS or CRES will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria, and the others will be graded by CTCAE V5.0
Measured: Up to 12 months since the initiation of MSLN targeted CAR T cell therapy
Incidence of dose limiting toxicities (DLTs)
Dose limiting toxicities are defined as MSLN targeted CAR T cell therapy related adverse events within the first 28 days that meet the following criteria: grade 3 or higher CRS or CRES, and any other grade 4 adverse events.
Measured: Up to 28 days since the initiation of MSLN targeted CAR T cell therapy
Secondary outcomes (6)
Number and copy number of MSLN targeted CAR T cell
Number and copy number of MSLN targeted CAR T cell are evaluated by number in peripheral blood and tumor tissue.
Measured: Up to 3 years
Objective response rate (ORR)
Objective response rate includes complete response and partial response defined by investigators according to RECIST 1.1or iRECIST criteria.
Measured: Up to 3 years
Progression Free Survival (PFS)
Progression Free Survival is defined as the time from the initiation of MSLN targeted CAR T cell therapy to documented disease progression or death.
Measured: Up to 3 years
Time to response (TTR)
TTR is defined as the time from the initiation of MSLN targeted CAR T cell therapy to first assessed CR or PR by investigators according to RECIST 1.1or iRECIST criteria.
Measured: Up to 3 years
Duration of response (DOR)
Duration of response is defined as the time from objective response until documented tumor progression among responders.
Measured: Up to 3 years
Overall Survival (OS)
Overall Survival is defined as the time from the initiation of MSLN targeted CAR T cell therapy to documented disease progression or death.
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2023
- Study start20 Jan 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced or Metastatic Solid TumorsStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Chinese PLA General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Responsible party
- Principal investigator, Han weidong, Chinese PLA General Hospital
- Investigators
- Yangbin Zhao, PhD, Study director, UTC Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05693844
- Sponsor's protocol ID
- CHN-PLAGH-BT-077
- Status last verified
- May 2024
- First submitted
- 27 Dec 2022
- Last updated
- 10 May 2024
- 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 10 May 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Pan-T Booster Co-expressing MSLN CAR T Cell Therapy in Advanced/Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT05693844
- Acronym / sponsor ID
- CHN-PLAGH-BT-077
- Conditions
- Advanced or Metastatic Solid Tumors
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 15 participants (estimated)
- Lead sponsor
- Chinese PLA General HospitalUniversity, hospital or other
- Collaborators
- UTC Therapeutics Inc.
- Study start
- 20 Jan 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 23 Jan 2023 (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.
In preclinical study, investigators have demonstrated that the newly developed pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. In this clinical trial, enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1×10^6 cells/kg based on the basic principle of dose escalation design, in order to evaluate the safety, feasibility, pharmacokinetics/pharmacodynamics, and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo.
Detailed description
In this study, investigators have developed a novel CAR T cell system targeting mesothelin (MSLN) antigen, termed as Pan-T booster (harbouring CD40 agonist and one T cell costimulator agonist) co-expressing MSLN CAR T cell. Preclinical study demonstrated that this novel pan-T booster co-expressing MSLN CAR T cell possess more powerful antitumor activity than previously reported MSLN-CAR T cells. In this clinical trial, enrolled patients receive an initial dose of pan-T booster co-expressing MSLN CAR T cells at 1×10^6 cells/kg based on the basic principle of dose escalation design, in order to evaluate the safety, feasibility, pharmacokinetics/pharmacodynamics, and efficacy of pan-T booster co-expressing MSLN CAR T cell in vivo. The level of CAR-T cell expansion and the duration of expansion are important determining factors for subsequent dose escalation infusions (3×10^6 cells/kg and 6×10^6 cells/kg). Repeated infusion, immune checkpoint inhibitor (such as anti-PD1/PD-L1) or local therapy (radiotherapy) are allowed when patients achieve clinical benefit and the level of CAR-T cell expansion declines to low level.
In the 3 patients receiving the first dose treatment, we observed high levels of expansion of both total T cells and CAR T cells in the PB after CAR T cell infusion (CAR T > 300 per microliter, total T cells reaching 10 times the number of CAR T cells), one patient experienced a grade 2 pulmonary toxicity and transient liver dysfunction during the CAR T cell expansion period (infusion 14 days later), transient marked enlargement of the spleen, and required to be treated with glucocorticoids and ruxolitinib to control T cell toxicity. Efficacy monitoring showed that some target lesion clearance or reduction could be achieved within 2-4 weeks after CAR T infusion. Based on these observations, it was concluded that low-dose CAR T infusion (CAR+T cells 1×10^6 cells/kg) could achieve the sufficient level of CAR T cell expansion, and the initially planned CAR T dose escalation was dispensable. Subsequent patients after May 10th, 2024, will all be treated using 1×10^6 cells/kg dose.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Pan-T booster co-expressing MSLN CAR T cell | Experimental | Biological: Pan-T booster co-expressing MSLN CAR T cell, Drug: Albumin-bound paclitaxel, Drug: Cyclophosphamide, Drug: FludarabineBefore the infusion of pan-T booster co-expressing MSLN CAR T cells, all enrolled patients need to undergo conditioning chemotherapy consisting of albumin-bound paclitaxel, cyclophosphamide, and fludarabine. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 1. Age from 18 to 75 years with estimated life expectancy >3 months.
- 2. Histopathological confirmed advanced or metastatic solid tumors failed to at least first-line treatment or initially diagnosed advanced/metastatic solid tumors that have no NCCN guideline recommended standard first-line therapy. Mesothelin antigen expression percentage >＝10%.
- 3. Have at least one measurable target lesion.
- 4. 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 rebiopsy in the process of this study.
- 5. 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)
- 1. Active, known or suspected autoimmune diseases.
- 2. 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.
- 3. Subjects are being treated with either corticosteroids (>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment.
- 4. History of severe hypersensitive reactions to other monoclonal antibodies.
- 5. 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 |
|---|---|---|
| Pan-T booster co-expressing MSLN CAR T cellStarting Dose: 1×10^6 cells/kg | Biological | Pan-T booster co-expressing MSLN CAR T cell |
| Albumin-bound paclitaxelAdministered intravenously at dose of 100-200mg/m2 on day -5 | Drug | Pan-T booster co-expressing MSLN CAR T cell |
| CyclophosphamideAdministered intravenously at a total dose of 15-30mg/kg on day -3 and day -2 | Drug | Pan-T booster co-expressing MSLN CAR T cell |
| FludarabineAdministered intravenously at dose of 30mg/m2/d on day -3 and day -2 | Drug | Pan-T booster co-expressing MSLN CAR T cell |
Primary outcome
Incidence of treatment related adverse events
Time frame: Up to 12 months since the initiation of MSLN targeted CAR T cell therapy
Treatment related adverse events are defined as any medical events since the initiation of MSLN targeted CAR T cell therapy . CRS or CRES will be graded based on American Society for Transplantation and Cellular Therapy (ASTCT) criteria, and the others will be graded by CTCAE V5.0
Incidence of dose limiting toxicities (DLTs)
Time frame: Up to 28 days since the initiation of MSLN targeted CAR T cell therapy
Dose limiting toxicities are defined as MSLN targeted CAR T cell therapy related adverse events within the first 28 days that meet the following criteria: grade 3 or higher CRS or CRES, and any other grade 4 adverse events.
6 secondary outcomes
Number and copy number of MSLN targeted CAR T cell
Time frame: Up to 3 years
Objective response rate (ORR)
Time frame: Up to 3 years
Progression Free Survival (PFS)
Time frame: Up to 3 years
Time to response (TTR)
Time frame: Up to 3 years
Duration of response (DOR)
Time frame: Up to 3 years
Overall Survival (OS)
Time frame: Up to 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 10 May 2024.
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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.
Yangbin Zhao, PhD study director
UTC Therapeutics Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Pan-T booster co-expressing MSLN CAR T cell, Albumin-bound paclitaxel and Cyclophosphamide in people with Advanced or Metastatic Solid Tumors, 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: looking for participants now, as of the sponsor's last update on 10 May 2024. 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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 Kaichao Feng, MD (+861066939460, timothyfkc@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment related adverse events (time frame: Up to 12 months since the initiation of MSLN targeted CAR T cell therapy). 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 10 May 2024; AzTrials last refreshed its copy on 6 Nov 2026.