Intratumoral Injection of Standard Universal Donor Expanded Natural Killer Cells and TGF-beta Imprinted Natural Killer Cells for the Treatment of Skin Squamous Cell Carcinoma and Basal Cell Carcinoma

Not Applicable

Recruiting

• Conditions: Skin Basal Cell Carcinoma; Skin Nodular Basal Cell Carcinoma; Skin Squamous Cell Carcinoma
• Interventions: Procedure: Biopsy Procedure; Biological: Natural Killer Cell Therapy; Procedure: Surgical Procedure; Biological: Universal Donor Expanded TGF-beta-imprinted NK Cells

• Registration Number: NCT07144384
• Lead Sponsor: Brittany Dulmage

Brief Summary

This early phase I trial compares the safety, side effects and the biological or cellular activity of two types of universal donor (UD) natural killer (NK) cells (standard NK cells and transforming growth factor \[TGF\] beta imprinted \[TGF-beta-i\] NK cells), given directly into the tumor (intratumoral) in treating patients with skin (cutaneous) squamous cell carcinoma (SCC) or basal cell carcinoma (BCC). NK cells are a type of white blood cell that can recognize missing or incorrect proteins on tumor cells and then kill these tumor cells. It was recently discovered that infection with human cytomegalovirus (CMV), a common virus, leads to the development of a unique NK cell population. These "adaptive" NK cells have a more potent anti-tumor killing action. The TGF-beta-i NK cells used in this study are created using donors whose blood tests positive for CMV exposure. This may make them more effective at killing tumor cells. Giving UD TGF-beta-i NK cells may be safe, tolerable and/or more effective than standard UD expanded NK cells in treating patients with SCC or BCC.

Detailed Description

PRIMARY OBJECTIVE:

I. To determine the persistence of NK cell infiltration within biopsy-proven keratinocyte carcinomas following intra-tumoral injection of universal donor NK cells versus (vs) TGFbeta-resistant NK cells in a cohort of patients prior to their standard of care excision.

SECONDARY OBJECTIVES:

I. To assess the tolerability of NK cell cutaneous intra-tumoral injection measured by adverse events, described using Common Terminology for Cancer Related Adverse Events (CTCAE version \[v\] 5).

II. To test the feasibility of a larger study using intra-tumorally injected NK cells.

EXPLORATORY/CORRELATIVE OBJECTIVES:

I. To assess clinical outcomes including size, area change, and visual appearance in clinical detection of keratinocyte carcinomas between injection and excision.

II. To compare NK and other immune cell presence within the tumor/tumor microenvironment (TME) in cutaneous basal cell carcinomas (BCCs) vs squamous cell carcinomas (SCCs) injected with NK vs TGFbetai cells prior to excision.

OUTLINE: Patients are randomized to 1 of 2 cohorts.

COHORT I: Patients undergo standard of care (SOC) biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.

COHORT II: Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.

Study Timeline

• Study First Submitted: 2025-08-12
• Study First Submitted QC: 2025-08-23
• Study First Posted: 2025-08-27
• Status Verified: 2025-10
• Study Start: 2025-10-16
• Last Update Submitted: 2025-10-22
• Last Update Posted: 2025-10-24
• Primary Completion: 2026-12-31
• Study Completion: 2026-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 40

Inclusion Criteria

• Ohio State University patients > 18 years old

• Diagnosis of ≥ 1cm keratinocyte carcinoma, accessible by intra-tumoral injection

• Confirmation of cutaneous SCC (cSCC) (10 patients total) or BCC (10 patients total) via diagnostic biopsy

  • BCC: Nodular or aggressive subtype
  • SCC: Well-differentiated or aggressive subtype with T1 or T2 staging by American Joint Committee on Cancer (AJCC) criteria

• Patient meets criteria for standard of care surgical treatment with either wide local excision or Moh's surgery

• Presence of residual clinical cancer ≥ 1cm at the time of baseline

• Willingness to follow up for residual cancer extirpation between 2-8 weeks after the injection

Exclusion Criteria

• Planned or concurrent radiation or systemic treatment for solid tumor or hematologic malignancy including chemotherapies or immunotherapies received within 6 weeks of trial enrollment. These include but are not limited to methotrexate, 5-fluorouracil, vismodegib, cepilimumab, pembrolizumab, nivolumab, ipilimumab for any skin malignancy

• < 18 years old

• A negative deep and peripheral margin status from the diagnostic biopsy

• Diagnostic biopsy with the following histopathologic characteristics:

  • BCC: Superficial subtype
  • SCC: SCC in situ (SCCIS)/Bowen disease, basosquamous, keratoacanthoma (KA)-type SCC, or tumor with > T2 staging by AJCC criteria

• Any skin disease or active infection in the same area that may confound assessments

• Inability to follow-up for definitive treatment (surgical excision)

• Any other comorbidity or complication that in the opinion of the investigator could make the patient unsafe to participate in the study, such as:

  • Active infection
  • Pregnant women, women who are likely to become pregnant or are breastfeeding
  • Patients who received any other investigational drugs within the 30 days prior to screening visit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort I (UD expanded NK cells)	Biopsy Procedure	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
Cohort I (UD expanded NK cells)	Natural Killer Cell Therapy	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
Cohort I (UD expanded NK cells)	Surgical Procedure	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
Cohort II (UD expanded TGFbetai NK cells)	Biopsy Procedure	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
Cohort II (UD expanded TGFbetai NK cells)	Universal Donor Expanded TGF-beta-imprinted NK Cells	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.
Cohort II (UD expanded TGFbetai NK cells)	Surgical Procedure	Patients undergo SOC biopsy on day 0 and within 4 weeks (days 10-28) receive UD expanded TGF-beta-i NK cells intratumorally. Patients undergo SOC excision 4-8 weeks (days 28-56) after biopsy.

Primary Outcome Measures

Name	Time	Method
Change in intratumoral natural killer (NK) cell content	Up to 2 weeks after locoregional injection of NK cells	Immunohistochemical and in vitro studies of tissue from the original biopsy and post-NK cell treated tumor specimens will be performed to assess NK cell infiltration of the tumor. Difference in NK cell density by CD56 staining in pre- versus post-intervention skin tumor tissue will be compared between tumors receiving NK versus transforming growth factor betai cell injections.

Secondary Outcome Measures

Name	Time	Method
Number of participants with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events version 5.0 criteria	Up to 8 weeks after biopsy	Will be assessed by Common Terminology Criteria for Adverse Events version 5.0 criteria. Will be summarized as the percentage of patients experiencing each type and grade of event according to dose level. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

Trial Locations

Locations (1)

Ohio State University Comprehensive Cancer Center; 🇺🇸 Columbus, Ohio, United States