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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)

Phase 3
Recruiting
Conditions
Melanoma
Interventions
Drug: relatlimab+nivolumab
Registration Number
NCT06246916
Lead Sponsor
Regeneron Pharmaceuticals
Brief Summary

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)

Detailed Description

Not available

Recruitment & Eligibility

Status
RECRUITING
Sex
All
Target Recruitment
560
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
relatlimab+nivolumabrelatlimab+nivolumabRandomized 1:1
fianlimab+cemiplimabfianlimabRandomized 1:1
fianlimab+cemiplimabcemiplimabRandomized 1:1
Primary Outcome Measures
NameTimeMethod
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
NameTimeMethod
Titer of ADAs to fianlimabUp to 72 months
Duration of Response (DOR) by BICRUp to 72 months
DOR by investigator assessmentUp to 72 months
Disease control rate (DCR) by BICRUp to 72 months
Death from any causeUp to 72 months
Overall survival (OS)Up to 72 months
PFS based on investigator assessment according to RECIST version 1.1Up to 72 months
Incidence of immune-mediated adverse events (imAEs)Up to 72 months
Occurrence of interruption of study drug(s) due to AEsUp to 72 months
Occurrence of discontinuation of study drug(s) due to AEsUp to 72 months
Progression free survival (PFS) RECIST version 1.1 based on BICRUp to 72 months
Incidence of treatment-emergent adverse events (TEAEs)Up to 72 months
Incidence of laboratory abnormalitiesUp to 72 months

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

Incidence of ADAs to cemiplimabUp to 72 months
Titer of ADAs to cemiplimabUp to 72 months
TEAEs leading to deathUp to 72 months
Incidence of NAbs to cemiplimabUp to 72 months
ORR based on investigator assessment according to RECIST version 1.1Up to 72 months
Incidence of serious adverse events (SAEs)Up to 72 months
Concentration of cemiplimab in serumUp to 72 months
Incidence of anti-drug antibodies (ADAs) to fianlimabUp to 72 months
Incidence of neutralizing antibodies (NAbs) to fianlimabUp to 72 months
Concentration of fianlimab in serumUp to 72 months
DCR by investigator assessmentUp to 72 months

Trial Locations

Locations (76)

Ironwood Cancer & Research Centers

🇺🇸

Chandler, Arizona, United States

Banner MD Anderson Cancer Center

🇺🇸

Gilbert, Arizona, United States

Arizona Oncology Associates

🇺🇸

Tucson, Arizona, United States

Cancer and Blood Specialty Clinic

🇺🇸

Los Alamitos, California, United States

UCLA

🇺🇸

Los Angeles, California, United States

Eisenhower Medical Center

🇺🇸

Rancho Mirage, California, United States

Sutter Health

🇺🇸

Sacramento, California, United States

UCSF

🇺🇸

San Francisco, California, United States

Sansum Clinic

🇺🇸

Santa Barbara, California, United States

St John's Cancer Institute

🇺🇸

Santa Monica, California, United States

Rocky Mountain Regional VA Medical Center

🇺🇸

Aurora, Colorado, United States

University of Colorado Cancer Center

🇺🇸

Aurora, Colorado, United States

The Melanoma And Skin Cancer Institute

🇺🇸

Englewood, Colorado, United States

UCHealth

🇺🇸

Fort Collins, Colorado, United States

Yale Cancer Center

🇺🇸

New Haven, Connecticut, United States

Clermont Oncology Center

🇺🇸

Clermont, Florida, United States

Cancer Specialist of North Florida

🇺🇸

Jacksonville, Florida, United States

Boca Raton Clinical Research (BRCR) Global

🇺🇸

Plantation, Florida, United States

H. Lee Moffitt Cancer Center

🇺🇸

Tampa, Florida, United States

John B. Amos Cancer Center

🇺🇸

Columbus, Georgia, United States

Beacon Clinic

🇺🇸

Coeur d'Alene, Idaho, United States

Hope and Healing Cancer Services

🇺🇸

Hinsdale, Illinois, United States

Advocate Lutheran General Hospital

🇺🇸

Park Ridge, Illinois, United States

Illinois CancerCare

🇺🇸

Peoria, Illinois, United States

Fort Wayne Medical Oncology and Hematology

🇺🇸

Fort Wayne, Indiana, United States

The University of Kansas Cancer Center

🇺🇸

Westwood, Kansas, United States

Markey Cancer Center Clinical Research Organization

🇺🇸

Lexington, Kentucky, United States

Mary Bird Perkins Cancer Center

🇺🇸

Baton Rouge, Louisiana, United States

Maryland Oncology Hematology, P.A.

🇺🇸

Columbia, Maryland, United States

Karmanos Cancer Institute

🇺🇸

Detroit, Michigan, United States

Minnesota Oncology Hematology, P.A

🇺🇸

Fridley, Minnesota, United States

Allina Health Cancer Institute

🇺🇸

Minneapolis, Minnesota, United States

VA St. Louis Healthcare System

🇺🇸

Saint Louis, Missouri, United States

Washington University

🇺🇸

Saint Louis, Missouri, United States

Mercy South

🇺🇸

Saint Louis, Missouri, United States

St. Vincent Healthcare

🇺🇸

Billings, Montana, United States

Oncology Hematology West P.C. dba Nebraska Cancer Specialists

🇺🇸

Omaha, Nebraska, United States

Comprehensive Cancer Centers of Nevada

🇺🇸

Las Vegas, Nevada, United States

John Theurer Cancer Center

🇺🇸

Hackensack, New Jersey, United States

Rutgers Cancer Institute of New Jersey

🇺🇸

New Brunswick, New Jersey, United States

New York Oncology Hematology

🇺🇸

Albany, New York, United States

Messino Cancer Center

🇺🇸

Asheville, North Carolina, United States

Levine Cancer Institute

🇺🇸

Charlotte, North Carolina, United States

Oncology Hematology Care Clinical Trials

🇺🇸

Cincinnati, Ohio, United States

Seidman Cancer Center

🇺🇸

Cleveland, Ohio, United States

Oklahoma Cancer Specialists and Research Institute, LLC

🇺🇸

Tulsa, Oklahoma, United States

Kaiser Foundation Hospitals

🇺🇸

Portland, Oregon, United States

St. Luke's University Health Network

🇺🇸

Easton, Pennsylvania, United States

Fox Chase Cancer Center

🇺🇸

Philadelphia, Pennsylvania, United States

University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center

🇺🇸

Pittsburgh, Pennsylvania, United States

Lifespan Cancer Institute

🇺🇸

Providence, Rhode Island, United States

Saint Francis Cancer Center

🇺🇸

Greenville, South Carolina, United States

Tennessee Oncology - Chattanooga

🇺🇸

Chattanooga, Tennessee, United States

University of Tennessee Medical Center

🇺🇸

Knoxville, Tennessee, United States

Sunnybrook Health Sciences Centre

🇨🇦

Toronto, Ontario, Canada

Princess Margaret Cancer Centre

🇨🇦

Toronto, Ontario, Canada

Sarah Cannon Research Institute (SCRI) Oncology Partners

🇺🇸

Nashville, Tennessee, United States

Tennessee Oncology

🇺🇸

Nashville, Tennessee, United States

Texas Oncology - Austin Central, Central Austin Cancer Center

🇺🇸

Austin, Texas, United States

Center For Disease And Blood Disorder

🇺🇸

Fort Worth, Texas, United States

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

🇨🇦

Quebec, Canada

The University of Texas MD Anderson Cancer Center

🇺🇸

Houston, Texas, United States

Joe Arrington Cancer Research & Treatment Center

🇺🇸

Lubbock, Texas, United States

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

🇺🇸

Tyler, Texas, United States

Texas Oncology-Tyler, Northeast Texas Cancer Institute

🇺🇸

Tyler, Texas, United States

University of Virginia

🇺🇸

Charlottesville, Virginia, United States

Virginia Cancer Specialists, PC

🇺🇸

Fairfax, Virginia, United States

Virginia Oncology Associates

🇺🇸

Norfolk, Virginia, United States

Virginia Commonwealth University Massey Cancer Center

🇺🇸

Richmond, Virginia, United States

Oncology & Hematology Associates of Southwest Virginia, Inc.

🇺🇸

Roanoke, Virginia, United States

Swedish Cancer Institute - Edmonds Campus

🇺🇸

Edmonds, Washington, United States

Swedish Cancer Institute - Issaquah Campus

🇺🇸

Issaquah, Washington, United States

Swedish Cancer Institute

🇺🇸

Seattle, Washington, United States

West Virginia University

🇺🇸

Morgantown, West Virginia, United States

University of Wisconsin Carbone Cancer Center

🇺🇸

Madison, Wisconsin, United States

London Regional Cancer Centre

🇨🇦

London, Ontario, Canada

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