Opdualag vs. Cemiplimab/Fianlimab in Relation to the Immunological Response in Tumor and Peripheral Blood in Unresectable or Metastatic Melanoma

Not yet recruiting

• Conditions: Locally Advanced Melanoma
• Interventions: Drug: Fianlimab + Cemiplimab; Drug: Relatlimab + Nivolumab

• Registration Number: NCT07223411
• Lead Sponsor: John Kirkwood

Brief Summary

This translational study will examine the immune effector responses of patients who received a two-drug combination for first line therapy by examining tumor and peripheral blood of participants with unresectable locally advanced or metastatic melanoma.

Detailed Description

Cutaneous melanoma is an aggressive skin cancer which, in the metastatic setting, has a historic 5-year survival rate of \<30%. In 2023, about 97,610 new cases of melanoma were estimated to occur in the US, with about 7,990 deaths. GLOBACON reported 324,635 cases of melanoma globally in 2020, which constituted about 1.7% of all cancers and 57,043 melanoma-associated deaths.

The parent trial of this corollary study is a randomized, open-label, multicenter phase 3 study comparing the anti-tumor activity of fixed-dose combination (FDC) of fianlimab + cemiplimab versus the FDC of relatlimab + nivolumab (referred to as Opdualag™) in participants with unresectable or metastatic melanoma (stage III-IV). This corollary study will explore the immunological response of CD8, CD4, and other immune cells in the blood and tumor microenvironment of patients in response to the provided treatments.

Study Timeline

• Status Verified: 2025-10
• Study First Submitted: 2025-10-30
• Study First Submitted QC: 2025-10-30
• Last Update Submitted: 2025-10-30
• Study First Posted: 2025-10-31
• Last Update Posted: 2025-10-31
• Study Start: 2025-11-01
• Primary Completion: 2028-11-01
• Study Completion: 2031-11-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

1. Study participants who meet inclusion criteria for the HCC 24-056 study will be eligible for this study.

2. Participants must be willing to provide additional samples beyond what is required of them in HCC 24-056. These include:

   1. 3 additional tumor biopsies
   2. 3 additional blood draws

3. Participants must have biopsiable non-target disease amenable to at least 3 biopsies.

4. Must have the ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria

1. Study participants who do not qualify to enroll in the HCC 24-056 study will not be eligible for this study.

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
fianlimab + cemiplimab	Fianlimab + Cemiplimab	Patients who received fianlimab + cemiplimab treatment under protocol NCT06246916.
Opdualag (relatlimab + nivolumab)	Relatlimab + Nivolumab	Patients who received Opdualag (relatlimab + nivolumab) under protocol NCT06246916.

Primary Outcome Measures

Name	Time	Method
Single-cell analysis of CD4+ T cells	Up to 39 months	Single-cell RNAseq analysis of CD8+ T cells and other immune cells in blood and tumor biopsies.

Secondary Outcome Measures

Name	Time	Method
Immunological response of CD4+ T cells	Up to 39 months	Single-cell analysis of CD4+ T cell (frequency) and other immune cells in blood and tumor biopsies. Analysis of single-cell RNA-seq data to obtain gene module scores for each CD4+ T cell or myeloid cell in whole blood and tumor biopsies will be classified as binary: 1 (co-expressing cytotoxic and exhaustion gene modules) or 0 (no co-expression).
Multiplexed immunofluorescence	Up to 39 months	Frequencies of major immune subsets in the tumor microenvironment. The density of immune cells relative to the total number of cells in the tumor tissue will be calculated for each patient.

Trial Locations

Locations (1)

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States