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

NCT ID: NCT06599619

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 30 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2025-02-20
• Study Completion Date: 2029-05-31

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.

Conditions

Melanoma

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Patients Treated with 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)

Single agent, adjuvant anti-PD1 therapy

Intervention Type: 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

Interventions

Single agent, adjuvant anti-PD1 therapy

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

Intervention Type: DRUG

Other Intervention Names

OPDIVO®; Keytruda; Pembrolizumab; Nivolumab

Eligibility Criteria

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.

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

Sponsors

Melanoma Research Foundation

OTHER

Sponsor Role: collaborator

VeyTel Inc.

UNKNOWN

Sponsor Role: collaborator

John Kirkwood

OTHER

Sponsor Role: lead

Responsible Party

John Kirkwood

Professor of Medicine, Immunology, and Dermatology

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

John M Kirkwood, MD

Role: PRINCIPAL_INVESTIGATOR

UPMC Hillman Cancer Center

Locations

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Danielle L Bednarz, RN

Role: CONTACT

bednarzdl@upmc.edu

(412) 623-1191

Amy Rose, RN

Role: CONTACT

kennaj@upmc.edu

4126478587

Facility Contacts

Danielle L Bednarz, RN

Role: primary

bednarzdl@upmc.edu

(412) 623-1191

Amy Rose, RN

Role: backup

kennaj@upmc.edu

4126478587

Other Identifiers

HCC 23-167

Identifier Type: -

Identifier Source: org_study_id