Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi

Recruiting

• Conditions: Melanoma
• Interventions: Drug: Single agent, adjuvant anti-PD1 therapy

• Registration Number: NCT06599619
• Lead Sponsor: John Kirkwood

Brief Summary

This study will examine the impact of anti-programmed cell death 1 (PD1) therapy given in the approved adjuvant therapeutic regimens upon the morphologic, histopathologic, molecular and immunologic as well as genomic features of atypical/dysplastic nevi (A/DN) in patients with a prior documented melanoma of Stages IIB, IIC, IIIA, IIIB, or IIIC and concurrent presence of two or more atypical nevi.

Detailed Description

Given the established efficacy of anti-PD1 therapy as an adjuvant treatment in both advanced nodal and earlier stage deep primary node negative melanoma, this study hypothesizes that anti-PD1 therapy may provide a basis for effective therapeutic prevention. To study if anti-PD1 therapy can help prevent the development of melanoma, this study will examine its effects upon atypical/dysplastic nevi, which are well established as non-obligate pre-cursor lesions that are markers of increased risk of melanoma. This single agent, adjuvant study will evaluate the impact of adjuvant anti-PD1 therapy on morphology, histopathology, immunologic/molecular features, and gene expression of atypical/dysplastic nevi present in patients with stage IIB-III melanoma. This study aims to determine if anti-PD1 therapy will increase CD8 T cell responses to melanoma antigens, resulting in immune surveillance and anti-tumor immune responses within A/DN. It postulates that in response to anti-PD1 therapy, the aggregate pigmentation of total nevi including atypical/dysplastic nevi and benign melanocytic nevi will decrease with a measurable morphologic response. This study also asserts that there will be histopathologic changes within A/DN including increased density of immune infiltrate and increased presence of regression features. Increased anti-tumor immune response measured by increased CD8, IFN-y, and PD-1 expression within nevi is anticipated, along with a decrease in genes involved in pathways of melanomagenesis, pigmentation, and inflammation.

Study Timeline

• Study First Submitted: 2024-09-13
• Study First Submitted QC: 2024-09-13
• Study First Posted: 2024-09-19
• Study Start: 2024-11-01
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-24
• Last Update Posted: 2025-03-28
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. Subjects must have at least two atypical nevi of ≥ 4 mm diameter.
2. Subjects must have a current documented history of melanoma.
3. Subject must be ≥ 18 years and if female of childbearing potential, must agree to practice effective contraception per institutional SOC if sexually active.
4. Subjects will have been deemed candidates for adjuvant therapy with single agent anti-PD1 therapy.
5. Subjects must give written informed consent to participate in this study with consent signed and dated prior to entry into trial.

Exclusion Criteria

1. Patients with non-malignant diseases or indications that would preclude the administration of anti-PD1 therapy such as significant immune suppression or active autoimmune disease requiring disease modifying, immunosuppressive therapy, will be ineligible.
2. Patients who have previously received anti-PD1 therapy
3. Patients with history of other active, non-melanoma cancers
4. Patients who are receiving other anti-neoplastic therapy.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Patients Treated with single agent, adjuvant anti-PD1 therapy	Single agent, adjuvant anti-PD1 therapy	Patients receiving single agent, adjuvant anti-PD1 therapy (given either as standard of care or as part of a separate investigational study)

Primary Outcome Measures

Name	Time	Method
Change in the aggregate pigmentation	Pre-treatment, up to 12 months	Percentage change in the total aggregate pigmentation including A/DN and benign melanocytic nevi. Percent change will be quantified from posterior trunk digital photographic images utilizing DermViz automated image comparison software.

Secondary Outcome Measures

Name	Time	Method
Change in predefined atypical nevi - size	Pre-treatment, up to 12 months	Change in size of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia.
Change in predefined atypical nevi - margin	Pre-treatment, up to 12 months	Change in margin of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia.
Change in predefined atypical nevi - pigmentation	Pre-treatment, up to 12 months	Change in pigmentation of predefined atypical nevi at the level of the individual nevus, as documented by dermoscopy. An expert clinician panel will evaluate pre- and post-treatment dermoscopic images in a blinded manner to score the visual features of nevus atypia.
Change in histopathologic features of A/DN - cellular infiltrate	Pre-treatment, up to 12 months	Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for the dendritic cell and lymphocytic cell immune infiltrate.
Change in histopathologic features of A/DN - regression features	Pre-treatment, up to 12 months	Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for regression features including fibrosis and vascularization.
Change in histopathologic features of A/DN - cytologic features	Pre-treatment, up to 12 months	Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for cytologic features including nuclear size and atypia.
Change in histopathologic features of A/DN - dysplastic features	Pre-treatment, up to 12 months	Histopathologic changes within atypical nevi that are biopsied will be assessed by an expert dermatopathologist for dysplastic features of nevi including cell architecture.

Trial Locations

Locations (1)

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States