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

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Investigational drug late phase More information Active drug More information Moderate burden on patient More information

Trial Details

Sponsor: Regeneron Pharmaceuticals (industry)

Phase: 3

Start date: Sept. 9, 2024

Planned enrollment: 560

Trial ID: NCT06246916
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More trial details at ClinicalTrials.gov More info

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chevron Show for: fianlimab (REGN3767)

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Goal: Compare the efficacy and safety of fixed-dose fianlimab plus cemiplimab versus the approved relatlimab plus nivolumab combination (Opdualag) as first-line therapy for unresectable stage III or stage IV melanoma. Additional goals include characterization of pharmacokinetics and immunogenicity of the investigational agents and detailed safety profiling, including immune-mediated toxicity.

Patients: Adults with histologically confirmed unresectable stage III or metastatic (stage IV) cutaneous melanoma, treatment-naive in the advanced setting, with measurable disease per RECIST 1.1, ECOG 0–1, adequate organ function, and known or testable BRAF V600 status. Key exclusions include uveal, acral, or mucosal melanoma; active/untreated brain metastases or spinal cord compression; significant autoimmune disease requiring systemic immunosuppression; prior checkpoint inhibitor therapy other than anti–PD-1/PD-L1 per protocol; uncontrolled HIV/HBV/HCV infection; history of myocarditis; and elevated baseline troponin >2× ULN.

Design: Multicenter, randomized, active-controlled, parallel-group phase 3 trial with 1:1 allocation to fianlimab plus cemiplimab or relatlimab plus nivolumab. Blinded independent central review is used for tumor assessments by RECIST 1.1. Planned enrollment is 560 participants.

Treatments: Experimental arm: fixed-dose fianlimab plus cemiplimab. Fianlimab is a fully human IgG4 monoclonal antibody targeting LAG-3, blocking its interaction with MHC class II to release inhibitory signaling on activated T cells and enhance antitumor immunity. In phase 1 melanoma studies combined with the anti–PD-1 antibody cemiplimab, objective response rates around 61% and median PFS about 13 months were observed in anti–PD-1–naive advanced melanoma; activity was lower after prior anti–PD-1 for advanced disease. Safety was broadly similar to PD-1 monotherapy but with a higher incidence of adrenal insufficiency; grade ≥3 TRAEs occurred in about 22%, with treatment discontinuation in approximately 13%. Control arm: relatlimab plus nivolumab, an approved fixed-dose combination of LAG-3 and PD-1 blockade for unresectable or metastatic melanoma.

Outcomes: Primary endpoint is objective response rate per RECIST 1.1 by blinded independent central review. Key secondary endpoints include PFS by BICR, overall survival, time to death from any cause, duration of response, disease control rate, and corresponding investigator-assessed endpoints. Safety endpoints include incidence of TEAEs, SAEs, immune-mediated AEs, lab abnormalities, treatment interruptions/discontinuations, and TEAEs leading to death. Pharmacokinetic endpoints measure serum concentrations of fianlimab and cemiplimab. Immunogenicity endpoints evaluate incidence and titers of anti-drug and neutralizing antibodies to both agents. Follow-up for efficacy and safety extends up to 72 months.

Burden on patient: Moderate. As a phase 3 immunotherapy trial with two IV combination regimens, patients can expect regular infusion visits, serial radiographic assessments per RECIST, and comprehensive safety monitoring including labs and cardiac markers as indicated. Additional burden arises from pharmacokinetic sampling and repeated immunogenicity blood draws over time. No mandated invasive procedures beyond standard-of-care imaging and labs are described, and there are no investigational oral agents, but the long follow-up period (up to 6 years) and immunotherapy-specific safety surveillance contribute to ongoing visit frequency and monitoring needs.

Last updated: Oct 2025

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Centre Hospitalier Universitaire de Quebec (CHUQ) - Centre Hospitalier de l'Universite Laval (CHUL)

Québec, G1J 0J9, Canada

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London Regional Cancer Centre

London, Ontario, N6A 5W9, Canada

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Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

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Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

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Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

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Ironwood Cancer & Research Centers

Chandler, Arizona, 85224, United States

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University of Arkansas for Medical Sciences

Little Rock, Arkansas, 72205, United States

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Cancer and Blood Specialty Clinic

Los Alamitos, California, 90720, United States

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Eisenhower Medical Center

Rancho Mirage, California, 92270, United States

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Providence Medical Foundation

Fullerton, California, 92835, United States

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Sansum Clinic

Santa Barbara, California, 93105, United States

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St John's Cancer Institute

Santa Monica, California, 90404, United States

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St. Joseph Hospital Orange

Orange, California, 92868, United States

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Sutter Health

Sacramento, California, 95816, United States

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University of California Los Angeles

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University of California San Francisco (UCSF)

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Rocky Mountain Regional VA Medical Center

Aurora, Colorado, 80045, United States

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The Melanoma And Skin Cancer Institute

Englewood, Colorado, 80113, United States

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UCHealth

Fort Collins, Colorado, 80528, United States

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University of Colorado Cancer Center

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Yale Cancer Center

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Boca Raton Clinical Research (BRCR) Global

Tamarac, Florida, 33321, United States

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Cancer Specialist of North Florida

Jacksonville, Florida, 32256, United States

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Clermont Oncology Center

Clermont, Florida, 34711, United States

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H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

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Mayo Clinic Florida

Jacksonville, Florida, 32224, United States

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John B. Amos Cancer Center

Columbus, Georgia, 31904, United States

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University Cancer & Blood Center

Athens, Georgia, 30607, United States

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Beacon Clinic

Coeur d'Alene, Idaho, 83815, United States

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Advocate Lutheran General Hospital

Park Ridge, Illinois, 60068, United States

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Hope and Healing Cancer Services

Hinsdale, Illinois, 60521, United States

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Illinois CancerCare

Peoria, Illinois, 61615, United States

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Fort Wayne Medical Oncology and Hematology

Fort Wayne, Indiana, 46825, United States

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The University of Kansas Cancer Center

Westwood, Kansas, 66205, United States

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Markey Cancer Center Clinical Research Organization

Lexington, Kentucky, 40536, United States

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Mary Bird Perkins Cancer Center

Baton Rouge, Louisiana, 70809, United States

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Maryland Oncology Hematology, P.A.

Columbia, Maryland, 21044, United States

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Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

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University of Michigan

Ann Arbor, Michigan, 48109, United States

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Allina Health Cancer Institute

Minneapolis, Minnesota, 55407, United States

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Minnesota Oncology Hematology, P.A

Fridley, Minnesota, 55432, United States

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Mercy South

St Louis, Missouri, 63128, United States

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VA St. Louis Healthcare System

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Washington University

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St. Vincent Healthcare

Billings, Montana, 59102, United States

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Oncology Hematology West P.C. dba Nebraska Cancer Specialists

Omaha, Nebraska, 68130, United States

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Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89148, United States

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John Theurer Cancer Center

Hackensack, New Jersey, 07601, United States

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Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08901, United States

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The Valley Hospital Inc.

Paramus, New Jersey, 07652, United States

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New York Oncology Hematology

Albany, New York, 12206, United States

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Duke Health System

Durham, North Carolina, 27710, United States

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Levine Cancer Institute

Charlotte, North Carolina, 28204, United States

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Messino Cancer Center

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Novant Health Cancer Institute

Charlotte, North Carolina, 28204, United States

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Novant Health Weisiger Cancer Institute - Charlotte

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Novant Health Zimmer Cancer Institute - Wilmington

Wilmington, North Carolina, 28401, United States

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Oncology Hematology Care Clinical Trials

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Seidman Cancer Center

Cleveland, Ohio, 44106, United States

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Oklahoma Cancer Specialists and Research Institute, LLC

Tulsa, Oklahoma, 74146, United States

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Oncology Associates of Oregon PC

Eugene, Oregon, 97401, United States

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Oregon Health and Science University

Portland, Oregon, 97239, United States

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Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

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St. Luke's University Health Network

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University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

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Lifespan Cancer Institute

Providence, Rhode Island, 02903, United States

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Saint Francis Cancer Center

Greenville, South Carolina, 29607, United States

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Sarah Cannon Research Institute (SCRI) Oncology Partners

Nashville, Tennessee, 37203, United States

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Tennessee Oncology

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Tennessee Oncology - Chattanooga

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University of Tennessee Medical Center

Knoxville, Tennessee, 37920, United States

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Center For Disease And Blood Disorder

Fort Worth, Texas, 76104, United States

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Joe Arrington Cancer Research & Treatment Center

Lubbock, Texas, 79410, United States

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Texas Oncology

Dallas, Texas, 75246, United States

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Texas Oncology - Austin Central, Central Austin Cancer Center

Austin, Texas, 78731, United States

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Texas Oncology - Austin Midtown, Midtown Medical Center I

Austin, Texas, 78705, United States

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Texas Oncology - Bedford

Bedford, Texas, 76022, United States

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Texas Oncology - Fort Worth

Fort Worth, Texas, 76104, United States

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Texas Oncology - Grapevine

Grapevine, Texas, 76051, United States

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Texas Oncology - Harlingen, Medical Arts Pavillion

Harlingen, Texas, 78550, United States

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Texas Oncology - Longview

Longview, Texas, 75601, United States

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Texas Oncology - McAllen

McAllen, Texas, 78503, United States

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Texas Oncology - Medical City

Dallas, Texas, 75230, United States

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Texas Oncology - Weslaco, Knapp Medical Plaza

Weslaco, Texas, 78596, United States

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Texas Oncology-Palestine Cancer Center

Palestine, Texas, 75801, United States

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Texas Oncology-Tyler, Northeast Texas Cancer Institute

Tyler, Texas, 75702, United States

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The University of Texas Health Science Center at Tyler D/B/A UT Health East Texas HOPE Cancer Center

Tyler, Texas, 75701, United States

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The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

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University of Utah Huntsman Cancer Institute

Salt Lake City, Utah, 84112, United States

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Oncology & Hematology Associates of Southwest Virginia, Inc.

Roanoke, Virginia, 24014, United States

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University of Virginia

Charlottesville, Virginia, 22908, United States

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Virginia Cancer Specialists, PC

Fairfax, Virginia, 22031, United States

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Virginia Commonwealth University Massey Cancer Center

Richmond, Virginia, 23298, United States

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Virginia Oncology Associates

Norfolk, Virginia, 23502, United States

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Swedish Cancer Institute

Seattle, Washington, 98104, United States

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Swedish Cancer Institute - Edmonds Campus

Edmonds, Washington, 98026, United States

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Swedish Cancer Institute - Issaquah Campus

Issaquah, Washington, 98029, United States

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West Virginia University

Morgantown, West Virginia, 26506, United States

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University of Wisconsin Carbone Cancer Center

Madison, Wisconsin, 53792, United States

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Arizona Oncology Associates

Tucson, Arizona, 85711, United States

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Status: Withdrawn

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