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Updated May 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

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

Anti-Mesothelin TNaive/SCM hYP218 (TNhYP218) CAR T Cells in Participants With Mesothelin-Expressing Solid Tumors Including Mesothelioma (NCT06885697) is a Phase 1 interventional studying Mesothelioma and Neoplasms, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Mesothelioma, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

Target enrollment of 100 participants puts this in the typical range for a Phase 2-style efficacy study or a moderate Phase 3 trial in a focused Mesothelioma subpopulation. At this scale, the study has enough statistical power to detect a clear treatment effect but is not the largest cohort in the field.

Who May Be Eligible (Plain English)

* Who May Qualify: 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 progressed on at least one FDA-approved systemic therapy considered standard of care for their tumor type. There is no limit on the number of prior treatment regimens. Note: Given the aggressive nature of pancreatic cancer, otherwise eligible individuals with this cancer type can undergo leukapheresis before or while they are getting their frontline treatment as long as they meet all other inclusion criteria. However, TNhYP218 CAR T cells will only be administered after progression on first line standard of care therapy. - 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) Renal - Creatinine OR: \<=1.5 X ULN OR ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
* INCLUSION CRITERIA: 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 progressed on at least one FDA-approved systemic therapy considered standard of care for their tumor type. There is no limit on the number of prior treatment regimens. Note: Given the aggressive nature of pancreatic cancer, otherwise eligible individuals with this cancer type can undergo leukapheresis before or while they are getting their frontline treatment as long as they meet all other inclusion criteria. However, TNhYP218 CAR T cells will only be administered after progression on first line standard of care therapy. * 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) Renal * Creatinine OR: \<=1.5 X ULN OR * Calculated(b) creatinine clearance (GFR can also be used in place of creatinine or CrCl) \>= 50 mL/min for participant with creatinine levels \> 1.5 X institutional ULN Coagulation * International normalized ratio (INR) OR prothrombin time (PT): \<=1.5 X ULN unless participant is receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended use of anticoagulants * Activated partial thromboplastin time (aPTT): \<=1.5 X ULN unless participant is receiving anticoagulant therapy if PT or aPTT is within therapeutic range of intended use of anticoagulants ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. 1. Criteria must be met without erythropoietin dependency and without packed red blood cell (pRBC) transfusion within last 2 weeks. 2. Creatinine clearance (CrCl) should be calculated per institutional standard. * Normal cardiac ejection fraction (\>= 45% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram. * Room air oxygen saturation of 90% or greater. * Treatment-related toxicities from prior treatments must be resolved to \<= grade 2. * Participants with CNS metastases, leptomeningeal disease or carcinomatous meningitis are eligible if they are asymptomatic, have completed their treatment for CNS disease and have recovered from the acute effects of radiation therapy or surgery prior to study entry. Participants must have radiographically stable CNS disease without associated edema at least three months prior to study entry. Additionally, participants have had to have discontinued corticosteroid treatment or non-prophylactic antiseizure medications for these metastases at least four weeks prior to study entry. * Participants of child-bearing potential and participants who can father children must agree to use highly effective contraception or abstinence. * Participants who are nursing or plan to nurse a child must agree to discontinue/postpone nursing for the duration of study therapy and for 12 months after the administration of the cell product or for 4 months from the time no evidence of persistence/gene modified cells is documented in the participant s blood. * Ability of participant to understand and the willingness to sign a written informed consent document. EXCLUSION CRITERIA: 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. * Electrocardiogram showing a QTc interval \> 450 msec in males and \> 470 msec in females (\> 80 msec for participants with bundle branch block). Either Fridericia s or Bazett s formula may be used to correct the QT interval. * Participant has active infection with HIV, hepatitis B virus, HCV, or HTLV as defined below: * Positive serology for HIV, HTLV-1, or HTLV-2. * Active hepatitis B infection as demonstrated by test for hepatitis B surface antigen. Participants who are hepatitis B surface antigen negative but are hepatitis B core antibody positive must have undetectable hepatitis B DNA and receive prophylaxis against viral reactivation. * Active hepatitis C infection as demonstrated by hepatitis C RNA test. Participants who are HCV antibody positive will be screened for HCV RNA by any reverse transcription PCR or branched DNA assay. If HCV antibody is positive, eligibility will be determined based on a negative screening RNA value. * Participant is pregnant or intends to be pregnant during the required period of contraception for participants of childbearing potential. * Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of treatment initiation * Participants with a history of seizure disorder unless due to now treated metastatic lesions. * Ongoing uncontrolled intercurrent illness, including but not limited to ongoing or active infection, that would impact participant safety or limit compliance with study requirements.

Treatments Being Tested

DEVICE

mesothelin expression testing

Assay done at screening to determine mesothelin expression levels

BIOLOGICAL

TNhYP217 CAR T Cells

Variable doses, administered intravenously on Day 0

DRUG

fludarabine

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

DRUG

cyclophosphamide

600 mg/m\^2 IV infusion. Daily x 3 doses on Day -6, -5, -4

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center
Bethesda, Maryland, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT06885697), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT06885697 clinical trial studying?

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… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT06885697?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT06885697?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT06885697. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT06885697. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.