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.
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.
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.