Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
Phase 1 Study With Dose Expansion of the Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma
2 other identifiers
interventional
100
1 country
1
Brief Summary
Background: Mesothelioma is an aggressive cancer that grows in the linings of the body; this can include the membranes that line the heart, lungs, and internal organs. Mesothelin (MSLN) is a protein that appears in high numbers in many tumors, including mesothelioma. Researchers are developing a new treatment that collects a person s own immune cells (T cells); the T cells are genetically modified to target and kill tumor cells with high levels of MSLN. Objective: To test a new treatment (TNhYP218 CAR T cells) in people with solid tumors including mesothelioma. Eligibility: People aged 18 and older with solid tumors including mesothelioma that returned or spread after standard treatment. Design: Participants will be screened. A small piece of tissue will be cut from a tumor (biopsy). The sample will be tested to see if it has enough MSLN. Participants will undergo leukapheresis: Blood will be taken from their body through a vein. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different vein. Participant s T cells will be modified in a lab to produce TNhYP218 CAR T cells. Participants will enter the hospital. For 7 days, they will receive drugs to prepare their bodies for the study treatment. TNhYP218 CAR T cells will be administered into a vein. Participants will remain in the hospital for at least 7 more days. After discharge, participants will have follow-up visits for 5 years. These visits may include imaging scans, blood and heart tests, and a new biopsy. Long-term follow-up will continue another 10 years.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_1
Started Jul 2025
Longer than P75 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
March 19, 2025
CompletedFirst Posted
Study publicly available on registry
March 20, 2025
CompletedStudy Start
First participant enrolled
July 8, 2025
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2034
ExpectedStudy Completion
Last participant's last visit for all outcomes
June 1, 2044
February 17, 2026
February 6, 2026
8.9 years
March 19, 2025
February 14, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Establish the recommended phase 2 dose (RP2D) of TNhYP218 CAR T cells based on dose-limiting toxicity (DLT) of defined adverse events (AEs).
The highest dose level below the maximum administered dose at which no more than 1 of 6 participants experience DLT from the initiation of CAR-T cell infusion (day 0) through day 28 after infusion (day 28).
DLT assessment will occur in participants in the dose escalation cohort daily on days 0-4, on day 7, on day 21 and during week 4.
Determine the preliminary objective response rate of TNhYP218 CAR T cells in a limited number of participants with mesothelioma treated at the recommended phase 2 dose.
The proportion of mesothelioma participants with partial response or complete response at the recommended phase 2 dose.
assessed based on imaging studies at weeks 4, 8, 12 then every 12 weeks through disease progression or week 108, whichever occurs first.
Secondary Outcomes (8)
Near term safety of autologous genetically modified TNhYP218 CAR T cells in adult study participants with mesothelin expressing unresectable, metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors.
Assessments will occur daily during lymphodepletion, on day of cell infusion (D0), D10, D21, every 2 weeks from W4 to W8, then every 4 weeks through W 24 or disease progression.
Long term safety of autologous genetically modified TNhYP218 CAR T cells in adult study participants with mesothelin expressing unresectable, metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors.
Monitored at baseline, weeks 4, 12, 24 and 48 after cell infusion and annually thereafter for up to 15 years if positive during year 1 or warranted based on clinical history collected annually during15 year follow-up.
Determine the objective response rate of TNhYP218 CAR T cells in participants with mesothelin expressing solid tumors treated at doses other than the RP2D
assessed based on imaging studies at weeks 4, 8, 12 then every 12 weeks through disease progression or week 108, whichever occurs first.
Determine progression free survival in participants with mesothelin expressing solid tumors
Assessed based on imaging studies at weeks 4, 8, 12 then every 12 weeks through disease progression or week 108, whichever occurs first.
Determine duration of response in participants with mesothelin expressing solid tumors
Assessed based on imaging studies at weeks 4, 8, 12 then every 12 weeks through disease progression or week 108, whichever occurs first.
- +3 more secondary outcomes
Study Arms (2)
1/Dose Escalation
EXPERIMENTALParticipants with mesothelin expressing tumors will undergo lymphodepletion and will receive TNhYP218 CAR T cells at escalating doses
2/Dose Expansion
EXPERIMENTALParticipants with mesothelioma will undergo lymphodepletion and will receive TNhYP218 CAR T cells at the RP2D determined in Arm 1
Interventions
Assay done at screening to determine mesothelin expression levels
Variable doses, administered intravenously on Day 0
30 mg/m\^2 IV infusion administered followed by cyclophosphamide on days both are given. Daily x 4 doses on Day -7, -6, -5 and -4
600 mg/m\^2 IV infusion. Daily x 3 doses on Day -6, -5, -4
Eligibility Criteria
You may qualify if:
- In order to be eligible to participate in this study, an individual must meet all of the following criteria. For this protocol, treatment initiation is defined as the first day of lymphodepleting chemotherapy.
- Participant must have unresectable, locally advanced, or metastatic, or recurrent mesothelioma and other mesothelin expressing solid tumors. For participants with mesothelioma only those with epithelioid or biphasic histology (with \>80% epithelioid component) will be eligible. The diagnosis will be confirmed by the Laboratory of Pathology, CCR, NCI.
- Participant must have at least 1 measurable lesion by RECIST version 1.1.
- Tumor must have MSLN positivity of 2+ to 3+ in \>= 50% cancer cells by immunohistochemistry on freshly collected biopsy or archival tissue.
- Age \>= 18 years.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Participants must have adequate organ and marrow function as defined below:
- System: Laboratory Value
- Hematological
- Hemoglobi: \>=9 g/dL(a)
- absolute neutrophil count: \>=1,500/mcL
- platelets: \>=100,000/mcL
- Hepatic
- total bilirubin: \<=2.5 X institutional ULN OR direct bilirubin ULN for participants with total bilirubin levels \>1.5 X ULN
- AST and ALT \<= 2.5 X institutional ULN (\<= 5 X ULN for participants with liver metastases)
- +16 more criteria
You may not qualify if:
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 14 days prior to leukapheresis and 21 days prior to lymphodepleting chemotherapy.
- Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation.
- Participants with any form of primary immunodeficiency (e.g. severe combined immunodeficiency).
- Participants with active or history of autoimmune or immune mediated disease such as multiple sclerosis, lupus, inflammatory bowel disease, rheumatoid arthritis, or small vessel vasculitis. NOTE: Participants with vitiligo, endocrine deficiencies including thyroiditis managed with replacement hormones including physiologic corticosteroids are eligible.
- History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine.
- Therapeutic doses of systemic corticosteroid therapy within 14 days prior to treatment initiation. Physiological doses of steroids (up to 5mg/day of prednisolone or equivalent) are allowed. Corticosteroid creams, ointments, and eye drops are allowed.
- Participants with lung fibrosis, inflammatory lung disease or evidence of pneumonitis on baseline imaging studies or medical history of these disorders.
- Participant has any other prior or concurrent malignancy with the following exceptions:
- Adequately treated basal cell or squamous cell carcinoma
- In situ carcinoma of the cervix or breast, treated curatively and without evidence of recurrence for at least 12 months prior to initiation of study therapy.
- Treated non-melanoma skin cancer.
- Stage 0 or 1 melanoma completely resected at least 12 months prior to initiation of study therapy.
- Successfully treated organ-confined prostate cancer with no evidence of progressive disease based on PSA levels and are not on active therapy.
- A primary malignancy which has been completely resected and in complete remission for \>= 5 years.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
National Institutes of Health Clinical Center
Bethesda, Maryland, 20892, United States
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Raffit Hassan, M.D.
National Cancer Institute (NCI)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NON RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SEQUENTIAL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 19, 2025
First Posted
March 20, 2025
Study Start
July 8, 2025
Primary Completion (Estimated)
June 1, 2034
Study Completion (Estimated)
June 1, 2044
Last Updated
February 17, 2026
Record last verified: 2026-02-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF
- Time Frame
- Data will be made available as soon as possible or at the time of associated publication. Data not published in a manuscript will be shared via public source once the data set completes QC.
- Access Criteria
- The scientific data will be findable by key words or MeSH terms used during publication of manuscripts.@@@@@@All scRNA seq data will be uploaded to dbGaP and accession numbers will be shared.
This study will comply with the NIH Data Management and Sharing (DMS) Policy, which applies to all new and ongoing NIH-funded research in the IRP, as of January 25, 2023, that is associated with a ZIA, with a clinical protocol that undergoes scientific review and/or will involve genomic data sharing.