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

NCT07631013 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2026-0260NCI-2026-04160
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Squamous Cell Carcinoma

Outcome Measures

Primary Outcomes (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

  Through study completion; an average of 1 year

Study Arms (1)

ESC/EXP: Phase 1 Part 1-ESC and Part 2-EXP Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK Cells

EXPERIMENTAL

Participants will receive 2 TGFBR2 TROP2 CAR/IL15 CAR injections on Day 0 and Day 21 at the assigned dose level

Drug: TROP2 CAR/IL-15 TGFBR2 KO NK cells

Interventions

TROP2 CAR/IL-15 TGFBR2 KO NK cells DRUG

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.

ESC/EXP: Phase 1 Part 1-ESC and Part 2-EXP Treatment with TROP2 CAR/IL-15 TGFBR2 KO NK Cells

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead

Study Sites (1)

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• UT MD Anderson Website

MeSH Terms

Conditions

Carcinoma, Squamous Cell

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Squamous Cell

Study Officials

• Moran Amit, MD,PHD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Moran Amit, MD,PHD

CONTACT

(713) 794-5304; mamit@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2026
• First Posted: June 5, 2026
• Study Start (Estimated): December 31, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2030
• Last Updated: June 11, 2026

Record last verified: 2026-06

Locations

US (1)