- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05693844
CD40 Ligand Expressing MSLN-CAR T Cell Therapy in MSLN Positive Advanced/Metastatic Solid Tumors
Phase I/II Study of CD40 Ligand Expressing MSLN-CAR T Cell Treatment in MSLN Positive Advanced/Metastatic Solid Tumors
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Kaichao Feng, MD
- Phone Number: +861066939460
- Email: timothyfkc@126.com
Study Contact Backup
- Name: Weidong Han, PhD
- Phone Number: +861066937463
- Email: hanwdrsw69@yahoo.com
Study Locations
-
-
Beijing
-
Beijing, Beijing, China, 100853
- Recruiting
- Kaichao Feng
-
Contact:
- Kaichao Feng, MD
- Phone Number: +861066937231
- Email: timothyfkc@126.com
-
Principal Investigator:
- Weidong Han, PhD
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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.
- 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.
Exclusion Criteria:
- 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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CD40 ligand expressing MSLN-CAR T cells
Enrolled participants will be given a preconditioning regimen before the infusion of CD40 ligand expressing MSLN-CAR T cells. Patients enrolled in dose 1 will be assigned to cohort 1 and cohort 2 respectively. Three patients in cohort 1 will be given albumin-bound paclitaxel plus cyclophosphamide as conditioning treatment. Another three patients will be enrolled into cohort 2 to receive albumin-bound paclitaxel plus cyclophosphamide and fludarabine. The final preconditioning regimen in the following dose levels will be determined by investigators according to the results from cohort 1 and 2, including controllable safety, CAR T cell expansion levels and superior persistence in PB. |
Administered intravenously at dose of 100-200mg/m2 on day -5
Administered intravenously at dose of 15-30mg/kg on day -3 and day -2
Dose escalation: Dose1 (1×10^6 cells/kg) .
Dose 2 (3×10^6 cells/kg) .Dose 3 (6×10^6 cells/kg) Dose expansion: RP2D
Administered intravenously at dose of 30mg/m2 on day -3 and day -2
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Incidence of treatment related adverse events
Time Frame: Up to 12 months since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Treatment related adverse events are defined as any medical events since the initiation of CAR-MSLN 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
|
Up to 12 months since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Incidence of dose limiting toxicities (DLTs)
Time Frame: Up to 28 days since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Dose limiting toxicities are defined as CD40 ligand expressing MSLN-CAR T cell 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.
|
Up to 28 days since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Determine the maximum tolerated dose (MTD)
Time Frame: Up to 28 days since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Maximum tolerated dose is determined as the highest dose that is less than or equal to 2 DLT among 6 subjects.
|
Up to 28 days since the initiation of CD40 ligand expressing MSLN-CAR T cell therapy
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number and copy number of CD40 ligand expressing MSLN-CAR T cells
Time Frame: Up to 3 years
|
Number and copy number of CD40 ligand expressing MSLN-CAR T cells are evaluated by number in peripheral blood and tumor tissue.
|
Up to 3 years
|
Objective response rate (ORR)
Time Frame: Up to 3 years
|
Objective response rate includes complete response and partial response defined by investigators according to RECIST 1.1or iRECIST criteria.
|
Up to 3 years
|
Progression Free Survival (PFS)
Time Frame: Up to 3 years
|
Progression Free Survival is defined as the time from the initiation of CD40 ligand expressing MSLN-CAR T cell therapy to documented disease progression or death.
|
Up to 3 years
|
Time to response (TTR)
Time Frame: Up to 3 years
|
TTR is defined as the time from the initiation of CD40 ligand expressing MSLN-CAR T cell therapy to first assessed CR or PR by investigators according to RECIST 1.1or iRECIST criteria.
|
Up to 3 years
|
Duration of response (DOR)
Time Frame: Up to 3 years
|
Duration of response is defined as the time from objective response until documented tumor progression among responders.
|
Up to 3 years
|
Overall Survival (OS)
Time Frame: Up to 3 years
|
Overall Survival is defined as the time from the initiation of CD40 ligand expressing MSLN-CAR T cell therapy to documented disease progression or death.
|
Up to 3 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Yangbin Zhao, PhD, UTC Therapeutics Inc.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Neoplasms
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Antirheumatic Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Alkylating
- Alkylating Agents
- Myeloablative Agonists
- Antineoplastic Agents, Phytogenic
- Cyclophosphamide
- Paclitaxel
- Albumin-Bound Paclitaxel
- Fludarabine
Other Study ID Numbers
- CHN-PLAGH-BT-077
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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