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Squamous Cell CarcinomaPhase 1NCT07631013

Phase 1 Study Of TROP2 CAR/IL-15 TGFBR2 KO NK Cell In Patients With Oral Premalignant Lesions

A Phase 1 study testing TROP2 CAR/IL-15 TGFBR2 KO NK cells in people with Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
Search all trials

Trial summary

This is a phase 1, single-arm, open-label, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of TGFBR2 TROP2 CAR/IL15 NK cells in patients with high-risk oral premalignant lesions. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Cell Carcinoma
What is being tested?
TROP2 CAR/IL-15 TGFBR2 KO NK cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
36 participants
Where
1 siteUnited States
Study dates
31 Dec 2026to 30 Jun 2030
Phase
Phase 1
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Subjects with diffuse or multifocal oral premalignant lesions are eligible for this study and must have a confirmed histologic diagnosis of oral epithelial dysplasia or oral intraepithelial neoplasia. Diffuse disease is defined as a single lesion measuring 2 cm in greatest dimension, and multifocal disease is defined as the presence of two or more spatially distinct premalignant lesions within the oral cavity. Patients with a history of histologically confirmed head and neck squamous cell carcinoma, including oral cavity squamous cell carcinoma, are eligible provided there is no evidence of active invasive malignancy at the time of enrollment. For patients without a prior history of oral cavity squamous cell carcinoma, eligible lesions must demonstrate high-risk histology, including moderate dysplasia, severe dysplasia, or carcinoma in situ; in patients with a prior history of oral cavity squamous cell carcinoma, dysplasia of any grade identified on prior resection specimens or surveillance biopsies is acceptable. Histologic evidence of oral epithelial dysplasia identified on prior oral cancer resection specimens or surveillance biopsies is acceptable. A visible, clinically measurable oral lesion, such as leukoplakia, erythroplakia, or other clinically apparent premalignant mucosal abnormality, must be present and accessible for intralesional injection and clinical assessment.
  • Age ≥18 years
  • Patient tumors must demonstrate TROP2 expression of 1+ as determined by IHC at the MDACC CAP and CLIA accredited Clinical Laboratories
  • ≥2 weeks from the last cytotoxic chemotherapy, ≥3 days from last TKI or other targeted therapies, and ≥3 months from any cell therapy for any malignancy at the time of consent.
  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
  • Life expectancy ≥3 months per PI or treating physician's discretion.
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  • Women of childbearing potential (WOCBP) must have a negative urine pregnancy test within 72 hours prior to initiation of lymphodepleting chemotherapy. If the urine pregnancy test cannot be confirmed as negative, a serum β-hCG test must be performed and must be negative prior to treatment initiation.
  • A WOCBP is defined (in Appendix 1) as a female who has experienced menarche (as early as 8 years of age) and has not undergone successful surgical sterilization or is not postmenopausal (defined as ≥12 consecutive months of amenorrhea without an alternative medical cause). Women will be considered not of childbearing potential if they have undergone hysterectomy, bilateral salpingo-oophorectomy, bilateral tubal ligation, or other permanent sterilization procedures, or have ovarian failure with follicle-stimulating hormone (FSH) and estradiol levels in the menopausal range, including those who have received whole pelvic radiation therapy. Due to the unknown effects of TROP2 CAR/IL-15 TGFBR2 KO NK cell therapy on a developing fetus, and because radiation therapy is contraindicated during pregnancy, women of childbearing potential and male participants with partners of childbearing potential must agree to use effective contraception prior to study entry, for the duration of study participation, and for 6 months following TROP2 CAR/IL-15 TGFBR2 KO NK cell injection. Acceptable methods of contraception include hormonal contraceptives (oral, injectable, implantable, transdermal, or vaginal ring), intrauterine devices (IUDs), surgical sterilization (tubal ligation or hysterectomy), partner vasectomy, or barrier methods (e.g., condoms) used with spermicide. Complete abstinence is acceptable if consistent with the participant's lifestyle; however, periodic abstinence, the rhythm method, and withdrawal are not acceptable.
  • Participants must agree to notify the treating physician immediately if pregnancy is suspected or confirmed during the study. Male participants must also notify the investigator if they father a child during the study period.
  • Male patients treated or enrolled on this protocol must agree to follow the contraceptive guidelines in Appendix 1 prior to study entry and for the duration of study participation and for 6 months post-TROP2 CAR/IL-15 TGFBR2 KO NK cell injection.
  • Patients must have measurable disease as defined above in 4.1.1. Patients must have adequate organ function as defined below Table 1. Adequate Organ Function Laboratory Values Systemic Function Test Laboratory Value Hematologic ANC ≥1500/µL Platelets ≥100,000/µL Hemoglobin ≥9.0 g/dLa Renal Creatinine ≤1.5 × ULNb OR CrCl by Cockcroft-Gault ≥45 mL/min for patients with creatinine formula >1.5 × ULNb Hepatic Total bilirubin ≤1.5 × ULN OR direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 × ULN AST and ALT ≤2.5 × ULN (≤5 × ULN for patients with liver metastases) Coagulation PT/INR ≤1.5 × ULN unless patient is receiving aPTT anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants ALT=alanine aminotransferase; ANC=absolute neutrophil count; aPTT=activated partial thromboplastin time; AST=aspartate aminotransferase; CrCl=creatinine clearance; INR=international normalized ratio; PT=prothrombin time; ULN=upper limit of normal.
  • Criteria must be met without erythropoietin dependency (and without packed red blood cell transfusion within last 2 weeks of the screening test) defined as an initiation or dose increase within 12 weeks prior to screening.Patients on a stable dose for >/= 12 weeks are permitted...
  • Serum creatinine and CrCl should be interpreted and calculated per institutional standard.
  • Left ventricular ejection fraction >50%.
  • Adequate respiratory reserve defined as dyspnea Grade 0 or 1 and saturated oxygen >92% in room air. See Table 2 for a grading scale of dyspnea per the CTCAE v6.0.
  • Table 2. Dyspnea grading scale. Grade 0 - No shortness of breath Grade 1 - Shortness of breath with moderate exertion Grade 2 - Shorness of breath with minimal exertion; limiting instrumental ADL Grade 3 - Shortness of breath at rest; liniting self-care ADL Grade 4 - Life-threatening consequences; urgent intervention indicated Grade 5 - Death
  • Prior treatment with TROP2-targeted therapy will be allowed.
  • Willing to undergo mandatory blood collections and biopsies as required by the study.
  • Willing to sign consent for long-term follow-up on protocol PA17-0483.
  • Willing to stay within a 2-hour drive (approximately 100-mile radius) of the study site during the first 4 weeks after the TROP2 CAR/IL-15 TGFBR2 KO NK cell injection.
  • Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Functional Classification. To be eligible for this trial, patients should be class 2B or better.
  • Ability to understand and the willingness to sign a written informed consent document.

Who cannot join

  • Pregnant, breastfeeding, or expecting to conceive within the projected duration of the study, starting with the screening visit through 6 months post TROP2 CAR/IL-15 TGFBR2 KO NK cell injection.
  • Patients must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline.
  • Patients with ≤Grade 2 neuropathy, alopecia, or other non-relevant AEs may be deemed eligible at the discretion of the principal investigator (PI)/co-PIs. If a patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to the start of lymphodepleting chemotherapy.
  • If patients receive RT within 2 weeks of the start of treatment, they must not require corticosteroids and must not have had radiation pneumonitis. Of note, patients with prior RT to the esophagus or with RT plans predicted to expose the esophagus to RT are excluded.
  • Has received a live vaccine within 6 weeks prior to TROP2 CAR/IL-15 TGFBR2 KO NK injection and agrees to not receive live vaccine for at least 24 months post-injection. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin, and typhoid vaccine. Seasonal influenza and COVID-19 vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
  • Prior CAR T or NK cell or other genetically modified T or NK cell therapy.
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  • Receiving chronic systemic steroid therapy (in doses exceeding 10 mg daily of prednisone equivalent).
  • Known active CNS metastases and/or carcinomatous meningitis. Patients with previously treated brain metastases may participate if they completed radiation therapy, are clinically stable, and without requirement of steroid treatment for at least 2 weeks prior to study enrollment.
  • History of interstitial lung disease (ILD) that required steroids or has current pneumonitis/ILD.
  • Active infection requiring systemic therapy.
  • Known human immunodeficiency virus (HIV) infection.
  • Known active or chronic hepatitis B or hepatitis C virus infection.
  • Known history of active tuberculosis (Mycobacterium tuberculosis).
  • History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the patient's participation for the full duration of the study, or is not in the best interest of the patient to participate, in the opinion of the treating investigator.
  • Clinically significant cardiovascular disease within 12 months prior to the start of lymphodepleting chemotherapy, including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, cerebrovascular event, or cardiac arrhythmia associated with hemodynamic instability. NOTE: medically controlled arrhythmia would be permitted.
  • Patients with bleeding or thrombotic disorders or at risk for severe hemorrhage. Patients with known deep vein thrombosis/pulmonary embolism who are on appropriate anticoagulation treatment are eligible.
  • Patients with a history of ≥Grade 3 stomatitis or mucositis with prior therapy.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Moran Amit, MD,PHD contact

(713) 794-5304

mamit@mdanderson.org

United States1 site
  • MD Anderson Cancer Center

    Houston, Texas, 77030

    Moran Amit, MD,PHD, 713-794-5304, mamit@mdanderson.org

    Moran Amit, MD,PHD

Other trials in United States

About this study

Official title: Phase 1 Dose Escalation And Expansion Study Of Intralesional TROP2-CAR/ IL15 TGFBR2 KO Engineered Cord Blood-Derived NK Cells In Patients With Diffused Or Multifocal Oral Premalignant Lesions

This is a phase 1, single-arm, open-label, dose-escalation and dose-expansion study designed to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary efficacy of TGFBR2 TROP2 CAR/IL15 NK cells in patients with high-risk oral premalignant lesions.

Read the detailed description

Primary Objective:

  • To characterize the safety and tolerability of TROP2 CAR/IL15 TGFBR KO NK cells in patients with high-risk oral premalignant lesions.

Secondary Objectives:

  • To determine the antitumor activity of TROP2 CAR/IL15 TGFBR KO NK cells.
  • To quantify the persistence of infused allogeneic donor CAR-transduced CB-derived NK cells in recipient.
  • To conduct comprehensive immune correlative studies by evaluating tissue and bloodbased biomarkers associated with response and resistance to TROP2 CAR/IL-15 TGFBR2 KO NK cell injection in part using longitudinal paired biopsies obtained at preinjection, Week 2, and Week 8 post-injection.
  • To obtain preliminary data on quality of life and patient experience.
Being tested
TROP2 CAR/IL-15 TGFBR2 KO NK cells
Medical subject headings
Carcinoma, Squamous Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TROP2 CAR/IL-15 TGFBR2 KO NK cellsDrug

    Participants will receive one of two doses of TROP2 CAR/IL-15 TGFBR2 KO NK injection on D0 and every three weeks thereafter, receive up to a total of 4 cycles at either dose.

Study groups in NCT07631013
Study groupRoleWhat they receive
ESC/EXP: Phase 1 Part 1-ESC and Part 2-EXP Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK CellsExperimentalParticipants will receive 2 TGFBR2 TROP2 CAR/IL15 CAR injections on Day 0 and Day 21 at the assigned dose level
Receives: Drug: TROP2 CAR/IL-15 TGFBR2 KO NK cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and Adverse Events (AEs)

    Incidence of Adverse Events, Graded According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version (v) 6.0

    Measured: Through study completion; an average of 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Jun 2026
  2. Study start31 Dec 2026 (estimated)
  3. Primary completion30 Jun 2028 (estimated)
  4. Study completion30 Jun 2030 (estimated)

Resources

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
Masking
None (open label)
Enrolment
36 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT07631013
Sponsor's protocol ID
2026-0260
Other IDs
NCI-2026-04160
Status last verified
Oct 2026
First submitted
31 May 2026
Last updated
3 Nov 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing TROP2 CAR/IL-15 TGFBR2 KO NK cells in people with Squamous Cell Carcinoma, run by M.D. Anderson Cancer Center at 1 site in United States.

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 23 inclusion and 17 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: opening soon, as of the sponsor's last update on 3 Nov 2026. 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 United States. 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?

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 Moran Amit, MD,PHD ((713) 794-5304, mamit@mdanderson.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and Adverse Events (AEs) (time frame: Through study completion; an average of 1 year). 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 3 Nov 2026.

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