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

NCT ID: NCT07144384

Last Updated: 2025-10-24

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-10-16
• Study Completion Date: 2026-12-31

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.

Conditions

Skin Basal Cell Carcinoma; Skin Nodular Basal Cell Carcinoma; Skin Squamous Cell Carcinoma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort I (UD expanded NK cells)

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.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo SOC biopsy

Natural Killer Cell Therapy

Intervention Type: BIOLOGICAL

Given UD expanded NK cells intratumorally

Surgical Procedure

Intervention Type: PROCEDURE

Undergo SOC excision

Cohort II (UD expanded TGFbetai 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.

Group Type: EXPERIMENTAL

Biopsy Procedure

Intervention Type: PROCEDURE

Undergo SOC biopsy

Surgical Procedure

Intervention Type: PROCEDURE

Undergo SOC excision

Universal Donor Expanded TGF-beta-imprinted NK Cells

Intervention Type: BIOLOGICAL

Given intratumorally

Interventions

Biopsy Procedure

Undergo SOC biopsy

Intervention Type: PROCEDURE

Natural Killer Cell Therapy

Given UD expanded NK cells intratumorally

Intervention Type: BIOLOGICAL

Surgical Procedure

Undergo SOC excision

Intervention Type: PROCEDURE

Universal Donor Expanded TGF-beta-imprinted NK Cells

Given intratumorally

Intervention Type: BIOLOGICAL

Other Intervention Names

Biopsy; BIOPSY_TYPE; Bx; Operation; Surgery; Surgery Type; Surgery, NOS; Surgical; Surgical Intervention; Surgical Interventions; Surgical Procedures; Type of Surgery; Allogeneic TGFBi Expanded NK Cells; UD TGF-betai NK Cells; Universal Donor TGF-beta Imprinted Expanded NK Cells

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brittany Dulmage

OTHER

Sponsor Role: lead

Responsible Party

Brittany Dulmage

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Brittany L Dulmage, MD

Role: PRINCIPAL_INVESTIGATOR

Ohio State University Comprehensive Cancer Center

Locations

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

The Ohio State University Comprehensive Cancer Center

Role: CONTACT

OSUCCCClinicaltrials@osumc.edu

800-293-5066

Facility Contacts

Brittany L. Dulmage, MD

Role: primary

Brittany.dulmage@osumc.edu

614-293-1707

Related Links

http://cancer.osu.edu

The Jamesline

Other Identifiers

NCI-2025-05655

Identifier Type: REGISTRY

Identifier Source: secondary_id

OSU-24311

Identifier Type: -

Identifier Source: org_study_id