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

John Kirkwood

Status: Enrolling

Conditions: Melanoma

Treatments: Drug: Single agent, adjuvant anti-PD1 therapy

Study type: Observational

Funder types: Other

Identifiers

NCT06599619

HCC 23-167

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

30 participants in 1 patient group

Patients Treated with single agent, adjuvant anti-PD1 therapy

Description:

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

Treatment:

Drug: Single agent, adjuvant anti-PD1 therapy