Clinical trial NCT06246916: 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)
Official title: A Phase 3 Study of Fixed Dose Combinations of Fianlimab and Cemiplimab Versus Relatlimab and Nivolumab in Participants With Unresectable or Metastatic Melanoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Melanoma
Keywords: Unresectable Melanoma
Metastatic Melanoma
Advanced Melanoma
Stage III
Stage IV
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2024-02-07
Enrollment: 560
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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)


Eligibility criteria: 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.

Primary outcomes:
measure: Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on blinded independent central review (BICR)
timeFrame: Up to 72 months
Secondary outcomes:
measure: Progression free survival (PFS) RECIST version 1.1 based on BICR
timeFrame: Up to 72 months
measure: Death from any cause
timeFrame: Up to 72 months
measure: Overall survival (OS)
timeFrame: Up to 72 months
measure: Duration of Response (DOR) by BICR
timeFrame: Up to 72 months
measure: DOR by investigator assessment
timeFrame: Up to 72 months
measure: Disease control rate (DCR) by BICR
timeFrame: Up to 72 months
measure: DCR by investigator assessment
timeFrame: Up to 72 months
measure: ORR based on investigator assessment according to RECIST version 1.1
timeFrame: Up to 72 months
measure: PFS based on investigator assessment according to RECIST version 1.1
timeFrame: Up to 72 months
measure: Incidence of treatment-emergent adverse events (TEAEs)
timeFrame: Up to 72 months
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 72 months
measure: Incidence of immune-mediated adverse events (imAEs)
timeFrame: Up to 72 months
measure: Occurrence of interruption of study drug(s) due to AEs
timeFrame: Up to 72 months
measure: Occurrence of discontinuation of study drug(s) due to AEs
timeFrame: Up to 72 months
measure: TEAEs leading to death
timeFrame: Up to 72 months
measure: Incidence of laboratory abnormalities
timeFrame: Up to 72 months
measure: Concentration of fianlimab in serum
timeFrame: Up to 72 months
measure: Concentration of cemiplimab in serum
timeFrame: Up to 72 months
measure: Incidence of anti-drug antibodies (ADAs) to fianlimab
timeFrame: Up to 72 months
measure: Titer of ADAs to fianlimab
timeFrame: Up to 72 months
measure: Incidence of ADAs to cemiplimab
timeFrame: Up to 72 months
measure: Titer of ADAs to cemiplimab
timeFrame: Up to 72 months
measure: Incidence of neutralizing antibodies (NAbs) to fianlimab
timeFrame: Up to 72 months
measure: Incidence of NAbs to cemiplimab
timeFrame: Up to 72 months
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Ironwood Cancer & Research Centers
state: Arizona
city: Gilbert
country: United States
facility: Banner MD Anderson Cancer Center
state: Arizona
city: Tucson
country: United States
facility: Arizona Oncology Associates
state: Arizona
city: Los Alamitos
country: United States
facility: Cancer and Blood Specialty Clinic
state: California
city: Los Angeles
country: United States
facility: UCLA
state: California
city: Rancho Mirage
country: United States
facility: Eisenhower Medical Center
state: California
city: Sacramento
country: United States
facility: Sutter Health
state: California
city: San Francisco
country: United States
facility: UCSF
state: California
city: Santa Barbara
country: United States
facility: Sansum Clinic
state: California
city: Santa Monica
country: United States
facility: St John's Cancer Institute
state: California
city: Aurora
country: United States
facility: Rocky Mountain Regional VA Medical Center
state: Colorado
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Englewood
country: United States
facility: The Melanoma And Skin Cancer Institute
state: Colorado
city: Fort Collins
country: United States
facility: UCHealth
state: Colorado
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Clermont
country: United States
facility: Clermont Oncology Center
state: Florida
city: Jacksonville
country: United States
facility: Cancer Specialist of North Florida
state: Florida
city: Plantation
country: United States
facility: Boca Raton Clinical Research (BRCR) Global
state: Florida
city: Tampa
country: United States
facility: H. Lee Moffitt Cancer Center
state: Florida
city: Columbus
country: United States
facility: John B. Amos Cancer Center
state: Georgia
city: Coeur d'Alene
country: United States
facility: Beacon Clinic
state: Idaho
city: Hinsdale
country: United States
facility: Hope and Healing Cancer Services
state: Illinois
city: Park Ridge
country: United States
facility: Advocate Lutheran General Hospital
state: Illinois
city: Peoria
country: United States
facility: Illinois CancerCare
state: Illinois
city: Fort Wayne
country: United States
facility: Fort Wayne Medical Oncology and Hematology
state: Indiana
city: Westwood
country: United States
facility: The University of Kansas Cancer Center
state: Kansas
city: Lexington
country: United States
facility: Markey Cancer Center Clinical Research Organization
state: Kentucky
city: Baton Rouge
country: United States
facility: Mary Bird Perkins Cancer Center
state: Louisiana
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Fridley
country: United States
facility: Minnesota Oncology Hematology, P.A
state: Minnesota
city: Minneapolis
country: United States
facility: Allina Health Cancer Institute
state: Minnesota
city: Saint Louis
country: United States
facility: VA St. Louis Healthcare System
state: Missouri
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Saint Louis
country: United States
facility: Mercy South
state: Missouri
city: Billings
country: United States
facility: St. Vincent Healthcare
state: Montana
city: Omaha
country: United States
facility: Oncology Hematology West P.C. dba Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Hackensack
country: United States
facility: John Theurer Cancer Center
state: New Jersey
city: New Brunswick
country: United States
facility: Rutgers Cancer Institute of New Jersey
state: New Jersey
city: Albany
country: United States
facility: New York Oncology Hematology
state: New York
city: Asheville
country: United States
facility: Messino Cancer Center
state: North Carolina
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Cincinnati
country: United States
facility: Oncology Hematology Care Clinical Trials
state: Ohio
city: Cleveland
country: United States
facility: Seidman Cancer Center
state: Ohio
city: Tulsa
country: United States
facility: Oklahoma Cancer Specialists and Research Institute, LLC
state: Oklahoma
city: Portland
country: United States
facility: Kaiser Foundation Hospitals
state: Oregon
city: Easton
country: United States
facility: St. Luke's University Health Network
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center
state: Pennsylvania
city: Providence
country: United States
facility: Lifespan Cancer Institute
state: Rhode Island
city: Greenville
country: United States
facility: Saint Francis Cancer Center
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology - Chattanooga
state: Tennessee
city: Knoxville
country: United States
facility: University of Tennessee Medical Center
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute (SCRI) Oncology Partners
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Central, Central Austin Cancer Center
state: Texas
city: Fort Worth
country: United States
facility: Center For Disease And Blood Disorder
state: Texas
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Lubbock
country: United States
facility: Joe Arrington Cancer Research & Treatment Center
state: Texas
city: Tyler
country: United States
facility: The University of Texas Health Science Center at Tyler D/B/A UT Health East Texas HOPE Cancer Center
state: Texas
city: Tyler
country: United States
facility: Texas Oncology-Tyler, Northeast Texas Cancer Institute
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, PC
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University Massey Cancer Center
state: Virginia
city: Roanoke
country: United States
facility: Oncology & Hematology Associates of Southwest Virginia, Inc.
state: Virginia
city: Edmonds
country: United States
facility: Swedish Cancer Institute - Edmonds Campus
state: Washington
city: Issaquah
country: United States
facility: Swedish Cancer Institute - Issaquah Campus
state: Washington
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
city: London
country: Canada
facility: London Regional Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Quebec
country: Canada
facility: Centre Hospitalier Universitaire de Quebec (CHUQ) - Centre Hospitalier de l'Universite Laval (CHUL)
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: