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 3RecruitingNCT06246916

Regeneron Pharmaceuticals560 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

560

Conditions

Melanoma

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (112)

Ironwood Cancer & Research Centers

Chandler, Arizona, United States

RECRUITING

Banner MD Anderson Cancer Center

Gilbert, Arizona, United States

RECRUITING

Arizona Oncology Associates

Tucson, Arizona, United States

WITHDRAWN

University of Arkansas for Medical Sciences

Little Rock, Arkansas, United States

Outcomes

Primary Outcomes

Objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 based on blinded independent central review (BICR)

Time frame: Up to 72 months

Secondary Outcomes

Progression free survival (PFS) RECIST version 1.1 based on BICR

Time frame: Up to 72 months

Death from any cause

Time frame: Up to 72 months

Overall survival (OS)

Time frame: Up to 72 months

Duration of Response (DOR) by BICR

Time frame: Up to 72 months

DOR by investigator assessment

Time frame: Up to 72 months

Disease control rate (DCR) by BICR

Time frame: Up to 72 months

DCR by investigator assessment

Time frame: Up to 72 months

ORR based on investigator assessment according to RECIST version 1.1

Time frame: Up to 72 months

PFS based on investigator assessment according to RECIST version 1.1

Time frame: Up to 72 months

Incidence of treatment-emergent adverse events (TEAEs)

Time frame: Up to 72 months

Incidence of serious adverse events (SAEs)

Time frame: Up to 72 months

Incidence of immune-mediated adverse events (imAEs)

Time frame: Up to 72 months

Occurrence of interruption of study drug(s) due to AEs

Time frame: Up to 72 months

Occurrence of discontinuation of study drug(s) due to AEs

Time frame: Up to 72 months

TEAEs leading to death

Time frame: 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

Time frame: Up to 72 months

Concentration of fianlimab in serum

Time frame: Up to 72 months

Concentration of cemiplimab in serum

Time frame: Up to 72 months

Incidence of anti-drug antibodies (ADAs) to fianlimab

Time frame: Up to 72 months

Titer of ADAs to fianlimab

Time frame: Up to 72 months

Incidence of ADAs to cemiplimab

Time frame: Up to 72 months

Titer of ADAs to cemiplimab

Time frame: Up to 72 months

Incidence of neutralizing antibodies (NAbs) to fianlimab

Time frame: Up to 72 months

Incidence of NAbs to cemiplimab

Time frame: Up to 72 months

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)

Overview

Conditions

Interventions

Eligibility

Locations (112)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts