Understanding Immunotherapy Resistance Mechanisms in Advanced Melanoma

Completed

• Conditions: Melanoma

• Registration Number: NCT02694965
• Lead Sponsor: Duke University

Brief Summary

Purpose of the study:

The investigators are proposing that melanomas which respond and develop eventual disease stability in response to checkpoint inhibitor immunotherapy undergo a genetic program promoting secondary resistance.

Detailed Description

Understanding these genetic alterations and the factors which contribute to this process would be critical for the identification of novel immunotherapeutic targets which may synergize with the T cell-targeted checkpoint inhibitors. Furthermore, this work promises to provide greater insight into tumor-mediated immune evasion mechanisms and primary immunotherapy resistance, potentially unveiling predictive markers of clinical response for our expanding arsenal of immune checkpoint inhibitor therapies.

Many patients who exhibit a response to the anti-PD-1 antibodies develop a prolonged course of disease stability which resembles the equilibrium phase of the previously proposed process of cancer immunoediting. This state of equipoise has been hypothesized to involve genetic alterations that promote immune evasion and, in some cases, lead to the development of tumor escape. Based on our data, the investigators propose that melanomas that develop a period of disease stability in response to anti-PD-1 immunotherapy exhibit genetic alterations that suppress the effectiveness of anti-tumor immunity. Our previous studies indicate that the tumor-derived factors that play a role in the paracrine signaling pathways capable of regulating nearby stromal cell populations are more likely to be critical immune regulators of the tumor microenvironment. Therefore, the investigators will focus our studies on those differentially expressed genes which encode soluble proteins using an available prediction algorithm. Those genes identified by this study to be differentially expressed in the melanoma tissues of patients demonstrating a clinical response to immune checkpoint inhibitor therapy will be further evaluated in transgenic autochthonous melanoma models.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-02-18
• Study First Submitted QC: 2016-02-24
• Study First Posted: 2016-03-01
• Primary Completion: 2023-06-07
• Study Completion: 2023-06-07
• Status Verified: 2023-08
• Last Update Submitted: 2024-02-12
• Last Update Posted: 2024-02-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 122

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Observational - Correlate changes in gene expression upon disease progression or recurrence	up to 3 years	Arm 1: Differential gene expression will be compared in samples from pre-treatment and disease progression.; Arm 2: Differential gene expression will be compared in samples from pre-treatment and disease recurrence.

Trial Locations

Locations (1)

Duke University Medical Center; 🇺🇸 Durham, North Carolina, United States