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

Dose-response Analysis of Nivolumab/Relatlimab in the Fixed-dosed Combination 'Opdualag' vs. Cemiplimab/Fianlimab in Relation to the Immunological Response in Tumor and Peripheral Blood for Participants With Unresectable or Metastatic Melanoma: A Corollary Study of HCC 24-056 (NCT06246916)

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.

Study Overview

• Status: Recruiting
• Conditions: Locally Advanced Melanoma
• Intervention / Treatment: Drug: Fianlimab + Cemiplimab; Drug: Relatlimab + Nivolumab

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 Type: Observational
• Enrollment (Estimated): 20

Contacts and Locations

• Study Contact: Name: Danielle L Bednarz, RN; Phone Number: 4126231191; Email: bednarzdl@upmc.edu
• Study Contact Backup: Name: Amy Rose, RN; Phone Number: 4126478587; Email: kennaj@upmc.edu

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC Hillman Cancer Center
      • Contact: Danielle L Bednarz, RN; Phone Number: 4126231191; Email: bednarzdl@upmc.edu
      • Contact: Amy Rose, RN; Phone Number: 4126478587; Email: kennaj@upmc.edu
      • Principal Investigator: John M Kirkwood, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Study participants who met inclusion criteria for clinical trial NCT06246916

Description

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
fianlimab + cemiplimab; Patients who received fianlimab + cemiplimab treatment under protocol NCT06246916.	Drug: Fianlimab + Cemiplimab; Patients treated with Fianlimab 1600 mg + Cemiplimab 350 mg under protocol NCT06246916
Opdualag (relatlimab + nivolumab); Patients who received Opdualag (relatlimab + nivolumab) under protocol NCT06246916.	Drug: Relatlimab + Nivolumab; Patients treated with Relatlimab 160 mg + Nivolumab 480 mg under protocol NCT06246916; Other Names: Opdualag

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Immunological response of CD4+ T cells	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).	Up to 39 months
Multiplexed immunofluorescence	Degree of immune infiltration 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.	Up to 39 months
Multiplexed immunofluorescence	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.	Up to 39 months

Collaborators and Investigators

• Sponsor: John Kirkwood
• Collaborators: Regeneron Pharmaceuticals
• Investigators: Principal Investigator: John M Kirkwood, MD, UPMC Hillman Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): November 19, 2025
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2031

Study Registration Dates

• First Submitted: October 30, 2025
• First Submitted That Met QC Criteria: October 30, 2025
• First Posted (Estimated): October 31, 2025

Study Record Updates

• Last Update Posted (Actual): November 26, 2025
• Last Update Submitted That Met QC Criteria: November 20, 2025
• Last Verified: November 1, 2025

More Information

Terms related to this study

• Keywords: immune checkpoint inhibitor; immunological response
• Additional Relevant MeSH Terms: Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Nivolumab; relatlimab; cemiplimab; Opdualag
• Other Study ID Numbers: HCC 25-009

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No