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NCT Number: NCT06599619

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

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.

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Key information

Conditions

Melanoma Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dysplastic Nevus Syndrome Genetic Diseases, Inborn Hereditary Sensory and Autonomic Neuropathies Heredodegenerative Disorders, Nervous System Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Germ Cell and Embryonal Neoplasms, Nerve Tissue Neoplastic Syndromes, Hereditary Nervous System Diseases Nervous System Malformations Neurodegenerative Diseases Neuroectodermal Tumors Neuroendocrine Tumors Neuromuscular Diseases Nevi and Melanomas Nevus Peripheral Nervous System Diseases Polyneuropathies Skin Diseases Skin Neoplasms Skin and Connective Tissue Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Observational

Primary location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location status: Recruiting

Location contact

Amy Rose, RN

CONTACT

[email protected]

4126478587

Danielle L Bednarz, RN

CONTACT

[email protected]

(412) 623-1191

John M Kirkwood, MD

PRINCIPAL_INVESTIGATOR

Urvashi M Joshi, MD

SUB_INVESTIGATOR

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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.
  • Patients who have previously received anti-PD1 therapy
  • Patients with history of other active, non-melanoma cancers
  • Patients who are receiving other anti-neoplastic therapy.

Treatment and study plan

Single agent, adjuvant anti-PD1 therapy

Drug

One of the following Single-agent, adjuvant anti-PD1 therapies:

Nivolumab is a type of targeted therapy drug called an immune checkpoint inhibitor (a type of immunotherapy). It is a monoclonal antibody that binds to the protein PD-1 on the surface of immune cells called T cells. It works by keeping cancer cells from suppressing the immune system.

Dose = 240 mg IV every 2 weeks/480 mg every 4 weeks or, Pembrolizumab is a monoclonal antibody and a type of immune checkpoint inhibitor that's used in cancer immunotherapy. It works by attaching to the PD-1 protein on the surface of T cells, which are immune cells. This prevents cancer cells from suppressing the immune system, allowing the immune system to attack and kill the cancer cells.

Dose = 200 mg IV every 3 weeks/ 400 mg every 6 weeks

Other names: OPDIVO®, Keytruda, Pembrolizumab, Nivolumab

Primary outcomes

  1. Change in the aggregate pigmentation

    Time frame: 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 outcomes

  1. Change in predefined atypical nevi - size

    Time frame: 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.

  2. Change in predefined atypical nevi - margin

    Time frame: 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.

  3. Change in predefined atypical nevi - pigmentation

    Time frame: 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.

  4. Change in histopathologic features of A/DN - cellular infiltrate

    Time frame: 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.

  5. Change in histopathologic features of A/DN - regression features

    Time frame: 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.

  6. Change in histopathologic features of A/DN - cytologic features

    Time frame: 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.

  7. Change in histopathologic features of A/DN - dysplastic features

    Time frame: 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.

Other outcomes

  1. Change in Expression of SOX-10 and BRAF

    Time frame: Pre-treatment, up to 12 months

    Quantify change in expression of key genes of melanomagenesis in A/DN in response to anti-PD1 therapy, measured via bulk RNA-sequencing performed on biopsied nevus specimens.

  2. Change in CD-8 T lymphocytes

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in T cell subsets will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

  3. Change in T-regs

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in regulatory T cells will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

  4. Change in IFN-y immune transcriptional signature

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in IFN-y immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

  5. Change in IL-6 immune transcriptional signature

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in Immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

  6. Change in IL-10 immune transcriptional signature

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. IL-10 immune transcriptional signature will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

  7. Change in PD1 expression

    Time frame: Pre-treatment, up to 12 months

    Changes in the immune microenvironment of A/DN in response to anti-PD1 therapy. Changes in PD1 expression will be quantified and compared pre- and post-treatment via multiplex IHC and multiplex IF performed on biopsied specimens.

Study contacts

Contact information is provided by the study sponsor or research team.

Amy Rose, RN

CONTACT

[email protected]

4126478587

Danielle L Bednarz, RN

CONTACT

[email protected]

(412) 623-1191

Sponsors and collaborators

Lead sponsor

John Kirkwood

Other

Collaborators

  • Melanoma Research Foundation
  • VeyTel Inc.

Registry information

Official study title

A Study of the Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Features of Atypical/Dysplastic Nevi in Patients With Stage IIB-IIIC Melanoma

Important dates

Study start
2025
Primary completion
2029
Study completion
2029
First posted
Sep 19, 2024
Registry last updated
Jan 26, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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