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

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: Not yet 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

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.

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.

4. Unknown v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) V600 mutation status as described in the protocol.

   Prior/Concomitant Therapy:

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

Study record dates

Study Major Dates

• Study Start (Estimated): June 7, 2024
• Primary Completion (Estimated): January 7, 2027
• Study Completion (Estimated): April 14, 2033

Study Registration Dates

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

Study Record Updates

• Last Update Posted (Estimated): February 7, 2024
• Last Update Submitted That Met QC Criteria: January 30, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Stage III; Stage IV; Advanced Melanoma; Metastatic Melanoma; Unresectable Melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Nivolumab; Cemiplimab; Relatlimab
• 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, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has 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