Clinical trial NCT06599619: Effects of Anti-PD1 Adjuvant Checkpoint Blockade Immunotherapy on Atypical/Dysplastic Nevi
Official 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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Melanoma
Keywords: anti-PD1 therapy
immune checkpoint blockade
dysplastic nevi
BRAF and NRAS mutations
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: Melanoma Research Foundation
name: VeyTel Inc.
First posted: 2024-09-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a prior documented melanoma of Stages IIB, IIC, IIIA, IIIB, or IIIC and concurrent presence of two or more atypical nevi who have received anti-programmed cell death 1 (PD1) therapy given in the approved adjuvant therapeutic regimens.

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.

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.

Primary outcomes:
measure: Change in the aggregate pigmentation
timeFrame: Pre-treatment, up to 12 months
Secondary outcomes:
measure: Change in predefined atypical nevi - size
timeFrame: Pre-treatment, up to 12 months
measure: Change in predefined atypical nevi - margin
timeFrame: Pre-treatment, up to 12 months
measure: Change in predefined atypical nevi - pigmentation
timeFrame: Pre-treatment, up to 12 months
measure: Change in histopathologic features of A/DN - cellular infiltrate
timeFrame: Pre-treatment, up to 12 months
measure: Change in histopathologic features of A/DN - regression features
timeFrame: Pre-treatment, up to 12 months
measure: Change in histopathologic features of A/DN - cytologic features
timeFrame: Pre-treatment, up to 12 months
measure: Change in histopathologic features of A/DN - dysplastic features
timeFrame: Pre-treatment, up to 12 months
Other outcomes:
measure: Change in Expression of SOX-10 and BRAF
timeFrame: Pre-treatment, up to 12 months
measure: Change in CD-8 T lymphocytes
timeFrame: Pre-treatment, up to 12 months
measure: Change in T-regs
timeFrame: Pre-treatment, up to 12 months
measure: Change in IFN-y immune transcriptional signature
timeFrame: Pre-treatment, up to 12 months
measure: Change in IL-6 immune transcriptional signature
timeFrame: Pre-treatment, up to 12 months
measure: Change in IL-10 immune transcriptional signature
timeFrame: Pre-treatment, up to 12 months
measure: Change in PD1 expression
timeFrame: Pre-treatment, up to 12 months
Locations:
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
Study officials:
affiliation: UPMC Hillman Cancer Center
name: John M Kirkwood, MD
role: PRINCIPAL_INVESTIGATOR
References: