A Study With Combinations of Anti-LAG-3 and Anti-PD-1 Antibodies in Adult Participants With Advanced or Metastatic Melanoma (Harmony Head-to-Head)

A Phase 3 Study of Fixed Dose Combinations of Fianlimab and Cemiplimab Versus Relatlimab and Nivolumab in Participants With Unresectable or Metastatic Melanoma

This study is researching an experimental drug called fianlimab (also known as REGN3767), combined with another medication called cemiplimab (also known as REGN2810), called "study drugs". The study is focused on patients with a type of skin cancer known as melanoma. The aim of the study is to see how safe and effective the combination of fianlimab and cemiplimab is in treating melanoma, in comparison with the combination of two medications, relatlimab and nivolumab, commercialized under the brand name Opdualag™ and approved for the treatment of melanoma in adults and children.

The study is looking at several other research questions, including:

• What side effects may happen from taking the study drugs.
• How much study drug is in the blood at different times.
• Whether the body makes antibodies against the study drugs (which could make the drug less effective or could lead to side effects)

Study Overview

• Status: Recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: fianlimab; Drug: cemiplimab; Drug: relatlimab+nivolumab

• Study Type: Interventional
• Enrollment (Estimated): 560
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Study Locations

• Canada
  • Québec, Canada, G1J 0J9
    • Recruiting
    • Centre Hospitalier Universitaire de Quebec (CHUQ) - Centre Hospitalier de l'Universite Laval (CHUL)
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Recruiting
      • London Regional Cancer Centre
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Jewish General Hospital - Main Address
• United States
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Recruiting
      • Ironwood Cancer & Research Centers
    • Gilbert, Arizona, United States, 85234
      • Recruiting
      • Banner MD Anderson Cancer Center
    • Tucson, Arizona, United States, 85711
      • Withdrawn
      • Arizona Oncology Associates
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • Recruiting
      • University of Arkansas for Medical Sciences
  • California
    • Fullerton, California, United States, 92835
      • Recruiting
      • Providence Medical Foundation
    • Los Alamitos, California, United States, 90720
      • Recruiting
      • Cancer and Blood Specialty Clinic
    • Los Angeles, California, United States, 90024
      • Recruiting
      • University of California Los Angeles
    • Orange, California, United States, 92868
      • Recruiting
      • St. Joseph Hospital Orange
    • Orange, California, United States, 92868
      • Recruiting
      • University of California Irvine, UCI Medical Center
    • Rancho Mirage, California, United States, 92270
      • Withdrawn
      • Eisenhower Medical Center
    • Redlands, California, United States, 92373
      • Recruiting
      • Emad Ibrahim, MD, Inc.
    • Sacramento, California, United States, 95816
      • Recruiting
      • Sutter Health
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California San Francisco (UCSF)
    • Santa Barbara, California, United States, 93105
      • Recruiting
      • Sansum Clinic
    • Santa Monica, California, United States, 90404
      • Recruiting
      • St John's Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Cancer Center
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • Rocky Mountain Regional VA Medical Center
    • Englewood, Colorado, United States, 80113
      • Recruiting
      • The Melanoma and Skin Cancer Institute
    • Fort Collins, Colorado, United States, 80528
      • Withdrawn
      • UCHealth
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Clermont, Florida, United States, 34711
      • Recruiting
      • Clermont Oncology Center
    • Jacksonville, Florida, United States, 32224
      • Recruiting
      • Mayo Clinic Florida
    • Jacksonville, Florida, United States, 32256
      • Recruiting
      • Cancer Specialist of North Florida
    • Tamarac, Florida, United States, 33321
      • Recruiting
      • Boca Raton Clinical Research (BRCR) Global
    • Tampa, Florida, United States, 33612
      • Recruiting
      • H. Lee Moffitt Cancer Center
  • Georgia
    • Athens, Georgia, United States, 30607
      • Recruiting
      • University Cancer & Blood Center
    • Columbus, Georgia, United States, 31904
      • Withdrawn
      • John B. Amos Cancer Center
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83815
      • Recruiting
      • Beacon Clinic
  • Illinois
    • Hinsdale, Illinois, United States, 60521
      • Recruiting
      • Hope and Healing Cancer Services
    • Park Ridge, Illinois, United States, 60068
      • Recruiting
      • Advocate Lutheran General Hospital
    • Peoria, Illinois, United States, 61615
      • Recruiting
      • Illinois CancerCare
  • Indiana
    • Fort Wayne, Indiana, United States, 46825
      • Recruiting
      • Fort Wayne Medical Oncology and Hematology
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Recruiting
      • The University of Kansas Cancer Center
  • Kentucky
    • Lexington, Kentucky, United States, 40536
      • Recruiting
      • Markey Cancer Center Clinical Research Organization
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Recruiting
      • Mary Bird Perkins Cancer Center
  • Maryland
    • Columbia, Maryland, United States, 21044
      • Recruiting
      • Maryland Oncology Hematology, P.A.
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
    • Detroit, Michigan, United States, 48201
      • Withdrawn
      • Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Recruiting
      • Henry Ford Cancer Institute/Henry Ford Health System
  • Minnesota
    • Fridley, Minnesota, United States, 55432
      • Recruiting
      • Minnesota Oncology Hematology, P.A
    • Minneapolis, Minnesota, United States, 55407
      • Recruiting
      • Allina Health Cancer institute
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Washington University
    • St Louis, Missouri, United States, 63128
      • Recruiting
      • Mercy South
    • St Louis, Missouri, United States, 63106
      • Recruiting
      • VA St. Louis Healthcare System
  • Montana
    • Billings, Montana, United States, 59102
      • Recruiting
      • St. Vincent Healthcare
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Oncology Hematology West P.C. dba Nebraska Cancer Specialists
  • Nevada
    • Las Vegas, Nevada, United States, 89148
      • Recruiting
      • Comprehensive Cancer Centers of Nevada
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Recruiting
      • Dartmouth Hitchcock Medical Center
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • Recruiting
      • John Theurer Cancer Center
    • New Brunswick, New Jersey, United States, 08901
      • Recruiting
      • Rutgers Cancer Institute of New Jersey
    • Paramus, New Jersey, United States, 07652
      • Recruiting
      • The Valley Hospital Inc.
  • New York
    • Albany, New York, United States, 12206
      • Recruiting
      • New York Oncology Hematology
  • North Carolina
    • Asheville, North Carolina, United States, 28806
      • Recruiting
      • Messino Cancer Center
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Cancer Institute
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Novant Health Weisiger Cancer Institute - Charlotte
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Health System
    • Wilmington, North Carolina, United States, 28401
      • Recruiting
      • Novant Health Zimmer Cancer Institute - Wilmington
  • Ohio
    • Cincinnati, Ohio, United States, 45242
      • Recruiting
      • Oncology Hematology Care Clinical Trials
    • Cleveland, Ohio, United States, 44106
      • Recruiting
      • Seidman Cancer Center
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • The Ohio State University Wexner Medical Center
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74146
      • Recruiting
      • Oklahoma Cancer Specialists and Research Institute, LLC
  • Oregon
    • Eugene, Oregon, United States, 97401
      • Recruiting
      • Oncology Associates of Oregon PC
    • Portland, Oregon, United States, 97239
      • Recruiting
      • Oregon Health and Science University
    • Portland, Oregon, United States, 97227
      • Recruiting
      • Kaiser Foundation Hospitals
  • Pennsylvania
    • Easton, Pennsylvania, United States, 18045
      • Recruiting
      • St. Luke's University Health Network
    • Philadelphia, Pennsylvania, United States, 19111
      • Recruiting
      • Fox Chase Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Recruiting
      • Lifespan Cancer Institute
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Withdrawn
      • Saint Francis Cancer Center
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Recruiting
      • Tennessee Oncology - Chattanooga
    • Knoxville, Tennessee, United States, 37920
      • Recruiting
      • University of Tennessee Medical Center
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Tennessee Oncology
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute (SCRI) Oncology Partners
  • Texas
    • Austin, Texas, United States, 78731
      • Recruiting
      • Texas Oncology - Austin Central, Central Austin Cancer Center
    • Austin, Texas, United States, 78705
      • Recruiting
      • Texas Oncology - Austin Midtown, Midtown Medical Center I
    • Bedford, Texas, United States, 76022
      • Recruiting
      • Texas Oncology - Bedford
    • Dallas, Texas, United States, 75246
      • Recruiting
      • Texas Oncology
    • Dallas, Texas, United States, 75230
      • Recruiting
      • Texas Oncology - Medical City
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Texas Oncology - Fort Worth
    • Fort Worth, Texas, United States, 76104
      • Recruiting
      • Center For Disease And Blood Disorder
    • Grapevine, Texas, United States, 76051
      • Recruiting
      • Texas Oncology - Grapevine
    • Harlingen, Texas, United States, 78550
      • Recruiting
      • Texas Oncology - Harlingen, Medical Arts Pavillion
    • Houston, Texas, United States, 77030
      • Recruiting
      • The University of Texas MD Anderson Cancer Center
    • Longview, Texas, United States, 75601
      • Recruiting
      • Texas Oncology - Longview
    • Lubbock, Texas, United States, 79410
      • Recruiting
      • Joe Arrington Cancer Research & Treatment Center
    • McAllen, Texas, United States, 78503
      • Recruiting
      • Texas Oncology - McAllen
    • Palestine, Texas, United States, 75801
      • Recruiting
      • Texas Oncology-Palestine Cancer Center
    • Tyler, Texas, United States, 75702
      • Recruiting
      • Texas Oncology-Tyler, Northeast Texas Cancer Institute
    • Tyler, Texas, United States, 75701
      • Withdrawn
      • The University of Texas Health Science Center at Tyler D/B/A UT Health East Texas HOPE Cancer Center
    • Weslaco, Texas, United States, 78596
      • Recruiting
      • Texas Oncology - Weslaco, Knapp Medical Plaza
  • Utah
    • Salt Lake City, Utah, United States, 84112
      • Recruiting
      • University of Utah Huntsman Cancer Institute
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Inova Schar Cancer Institute
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists, PC
    • Norfolk, Virginia, United States, 23502
      • Recruiting
      • Virginia Oncology Associates
    • Richmond, Virginia, United States, 23298
      • Recruiting
      • Virginia Commonwealth University Massey Cancer Center
    • Roanoke, Virginia, United States, 24014
      • Recruiting
      • Oncology & Hematology Associates of Southwest Virginia, Inc.
  • Washington
    • Edmonds, Washington, United States, 98026
      • Recruiting
      • Swedish Cancer Institute - Edmonds Campus
    • Issaquah, Washington, United States, 98029
      • Recruiting
      • Swedish Cancer Institute - Issaquah Campus
    • Kennewick, Washington, United States, 99336
      • Recruiting
      • Kadlec Clinic Hematology and Oncology
    • Seattle, Washington, United States, 98104
      • Recruiting
      • Swedish Cancer Institute
  • West Virginia
    • Morgantown, West Virginia, United States, 26506
      • Recruiting
      • West Virginia University
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • Recruiting
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. Participants with histologically confirmed unresectable stage III and stage IV (metastatic) melanoma per American Joint Committee on Cancer (AJCC), eighth revised edition.
2. Participants must not have received prior systemic therapy for unresectable or metastatic melanoma as described in the protocol.
3. Measurable disease per RECIST version 1.1.
4. Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤1
5. Adequate bone marrow, hepatic, and kidney function
6. Known B-Rapidly Accelerated Fibrosarcoma protein (BRAF) V600 mutation status or submitted sample for BRAF V600 mutation assessment as described in the protocol

Key Exclusion Criteria:

Medical Conditions:

1. Uveal, acral or mucosal melanoma.
2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents as described in the protocol.

3. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B (HBV), or hepatitis C virus (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection. Mild cancer-related immunodeficiency (such as immunodeficiency treated with gamma globulin and without chronic or recurrent infection) is allowed.

   Prior/Concomitant Therapy:

4. Prior immune checkpoint inhibitor therapy other than anti-PD1/PD-L1 as described in the protocol

5. Systemic immune suppression as described in the protocol.

   Other Comorbidities:

6. Participants with a history of myocarditis.
7. Troponin T (TnT) or troponin I (TnI) >2x institutional upper limit of normal (ULN).
8. Active or untreated brain metastases or spinal cord compression as described in the protocol.

Note: Other protocol-defined Inclusion/ Exclusion Criteria apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: fianlimab+cemiplimab; Randomized 1:1	Drug: fianlimab; Intravenous (IV) administration every 3 weeks (Q3W) in combination with cemiplimab; Other Names: REGN3767; Drug: cemiplimab; IV administration Q3W in combination with fianlimab; Other Names: REGN2810; LIBTAYO®
Active Comparator: relatlimab+nivolumab; Randomized 1:1	Drug: relatlimab+nivolumab; IV administration every 4 weeks (Q4W); Other Names: Opdualag™

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on blinded independent central review (BICR)	Up to 72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression free survival (PFS) RECIST version 1.1 based on BICR		Up to 72 months
Death from any cause		Up to 72 months
Overall survival (OS)		Up to 72 months
Duration of Response (DOR) by BICR		Up to 72 months
DOR by investigator assessment		Up to 72 months
Disease control rate (DCR) by BICR		Up to 72 months
DCR by investigator assessment		Up to 72 months
ORR based on investigator assessment according to RECIST version 1.1		Up to 72 months
PFS based on investigator assessment according to RECIST version 1.1		Up to 72 months
Incidence of treatment-emergent adverse events (TEAEs)		Up to 72 months
Incidence of serious adverse events (SAEs)		Up to 72 months
Incidence of immune-mediated adverse events (imAEs)		Up to 72 months
Occurrence of interruption of study drug(s) due to AEs		Up to 72 months
Occurrence of discontinuation of study drug(s) due to AEs		Up to 72 months
TEAEs leading to death		Up to 72 months
Incidence of laboratory abnormalities	Grade ≥3 per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE v5.0) including standard hematology, chemistry, urinalysis, and other lab tests	Up to 72 months
Concentration of fianlimab in serum		Up to 72 months
Concentration of cemiplimab in serum		Up to 72 months
Incidence of anti-drug antibodies (ADAs) to fianlimab		Up to 72 months
Titer of ADAs to fianlimab		Up to 72 months
Incidence of ADAs to cemiplimab		Up to 72 months
Titer of ADAs to cemiplimab		Up to 72 months
Incidence of neutralizing antibodies (NAbs) to fianlimab		Up to 72 months
Incidence of NAbs to cemiplimab		Up to 72 months

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Publications and helpful links

Helpful Links

• Study Informational Website

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2024
• Primary Completion (Estimated): March 22, 2027
• Study Completion (Estimated): July 10, 2033

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Stage III; Stage IV; Advanced Melanoma; Metastatic Melanoma; Unresectable Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin Neoplasms; Skin and Connective Tissue Diseases; Melanoma; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; cemiplimab; Opdualag
• Other Study ID Numbers: R3767-ONC-22122

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

IPD Sharing Time Frame

When Regeneron has:

• received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• ensured the ability to protect participant privacy.

• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

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