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

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат 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

Первичные конечные точки

• Change in the aggregate pigmentation [Срок оценки: Pre-treatment, up to 12 months]

Вторичные конечные точки (7)

• Change in predefined atypical nevi - size [Срок оценки: Pre-treatment, up to 12 months]
• Change in predefined atypical nevi - margin [Срок оценки: Pre-treatment, up to 12 months]
• Change in predefined atypical nevi - pigmentation [Срок оценки: Pre-treatment, up to 12 months]
• Change in histopathologic features of A/DN - cellular infiltrate [Срок оценки: Pre-treatment, up to 12 months]
• Change in histopathologic features of A/DN - regression features [Срок оценки: Pre-treatment, up to 12 months]
• Change in histopathologic features of A/DN - cytologic features [Срок оценки: Pre-treatment, up to 12 months]
• Change in histopathologic features of A/DN - dysplastic features [Срок оценки: Pre-treatment, up to 12 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

США · 1 центр

• UPMC Hillman Cancer Center — Pittsburgh

Идентификаторы

NCT: NCT06599619 · HCC 23-167

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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