A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma

A Phase 2 Peri-operative Trial of Fianlimab and Cemiplimab Compared With Anti-PD1 Alone in Patients With Resectable Stage III and IV Melanoma

This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with cemiplimab alone. These types of immunotherapy study drugs are collectively known as immune checkpoint inhibitors. Immunotherapies are treatments that use the immune system to recognize and kill cancer cells. The study is focused on participants with a type of skin cancer known as melanoma.

The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to cemiplimab in participants with high-risk, resectable melanoma. Participants will receive treatment before surgery, undergo resection, and then will have the option to continue treatment after resection.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drug(s).
• How much study drug(s) is in the blood at different times.
• Whether the body makes antibodies against the study drug(s) (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in the blood stream that fight infections.
• How administering the study drugs might improve quality of life.

Study Overview

• Status: Active, not recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: Placebo; Drug: cemiplimab; Drug: Fixed Dose Combination (FDC) cemiplimab+fianlimab

• Study Type: Interventional
• Enrollment (Actual): 151
• Phase: Phase 2

Contacts and Locations

Study Locations

• Australia
  • New South Wales
    • Lismore, New South Wales, Australia, 2480
      • Lismore Base Hospital
    • Westmead, New South Wales, Australia, 2145
      • Westmead Hospital
    • Wollstonecraft, New South Wales, Australia, 2065
      • Melanoma Institute of Australia
  • Queensland
    • Douglas, Queensland, Australia, 4814
      • The Townsville Hospital
    • Hervey Bay, Queensland, Australia, 4655
      • Hervey Bay Hospital
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Flinders Medical Centre
    • Woodville, South Australia, Australia, 5011
      • The Queen Elizabeth Hospital
  • Tasmania
    • Hobart, Tasmania, Australia, 7000
      • Icon Cancer Centre Hobart
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Eastern Health
    • Melbourne, Victoria, Australia, 3052
      • Peter Maccallum Cancer Centre
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • One Clinical Research at Hollywood Private Hospital
• Austria
  • Vienna, Austria, 1090
    • Medical University of Vienna
  • Lower Austria
    • Sankt Pölten, Lower Austria, Austria, 3100
      • University Hospital Saint Poelten
  • Styria
    • Graz, Styria, Austria, 8036
      • Medical University of Graz
  • Tyrol
    • Innsbruck, Tyrol, Austria, 6020
      • Medical University Innsbruck
• Canada
  • Québec, Canada, G1J 1Z4
    • CHU de Québec - Université Laval
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Sunnybrook Health Sciences Centre
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C1
      • Centre Hospitalier de l'Universite de Montreal (CHUM)
• France
  • Boulogne, France, 92104
    • Hopital Ambroise Pare
  • Clermont-Ferrand, France, 63003
    • CHU Estaing
  • Lille, France, 59037
    • Regional University Hospital of Lille 2208
  • Marseille, France, 13385
    • Hôpital Timone
  • Nice, France, 06202
    • Centre Hospitalier Universitaire De Nice Hopital De L Archet
  • Auvergne-Rhône-Alpes
    • Pierre-Bénite, Auvergne-Rhône-Alpes, France, 69495
      • Hospices Civils de Lyon
  • Bourgogne-Franche-Comté
    • Dijon, Bourgogne-Franche-Comté, France, 21000
      • Centre Georges Francois Leclerc
  • Burgundy
    • Dijon, Burgundy, France, 21000
      • CHU-Dijon
  • Centre-Val de Loire
    • Tours, Centre-Val de Loire, France, 37044
      • CHRU de Tours
  • Gironde
    • Bordeaux, Gironde, France, 33075
      • CHU de Bordeaux
  • Isere
    • La Tronche, Isere, France, 38700
      • Centre Hospitalier Universitaire Grenoble Alpes
  • Normandy
    • Caen, Normandy, France, 14000
      • Centre Francois Baclesse
  • Nouvelle-Aquitaine
    • Poitiers, Nouvelle-Aquitaine, France, 86000
      • Centre Hospitalier Universitaire de Poitiers
  • Pays de la Loire Region
    • Nantes, Pays de la Loire Region, France, 44093
      • Nantes University Hospital
  • Île-de-France Region
    • Paris, Île-de-France Region, France, 75010
      • Saint Louis Hospital
    • Villejuif, Île-de-France Region, France, 94800
      • Gustave Roussy
• Germany
  • Berlin, Germany, 10117
    • Charite University Medicine
  • Bremen, Germany, 28325
    • Klinikum Bremen Ost
  • Baden-Wurttemberg
    • Freiburg im Breisgau, Baden-Wurttemberg, Germany, 79104
      • Universitätsklinikum Freiburg
    • Ulm, Baden-Wurttemberg, Germany, 89081
      • Universitätsklinikum Ulm
  • Bavaria
    • Munich, Bavaria, Germany, 80337
      • LMU Klinikum
    • Regensburg, Bavaria, Germany, 93053
      • University Hospital of Regensburg
    • Würzburg, Bavaria, Germany, 97080
      • Universitaetsklinikum Wuerzburg
  • Hesse
    • Giessen, Hesse, Germany, 35385
      • University Hospital Giessen
  • Lower Saxony
    • Buxtehude, Lower Saxony, Germany, 21614
      • Elbekliniken Stade Buxtehude
  • North Rhine-Westphalia
    • Bochum, North Rhine-Westphalia, Germany, 44791
      • Muhlenkreiskliniken Minden, Ruhr University Bochum
    • Essen, North Rhine-Westphalia, Germany, 45147
      • University Hospital Essen
  • Rhineland-Palatinate
    • Ludwigshafen am Rhein, Rhineland-Palatinate, Germany, D-67063
      • Hautklinik
  • Saxony
    • Dresden, Saxony, Germany, 01307
      • University Hospital Dresden
    • Leipzig, Saxony, Germany, 04103
      • Universitatsklinikum Leipzig, AoR
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23538
      • Universitatsklinikum Schleswig Holstein Campus Luebeck
  • Thuringia
    • Erfurt, Thuringia, Germany, D-99089
      • Helios Klinikum Erfurt
    • Gera, Thuringia, Germany, 07548
      • SRH Wald- Klinikum Gera GmbH
• Italy
  • Cuneo, Italy, 12100
    • Azienda Ospedaliera Santa Croce i Carle
  • Ferrara, Italy, 44124
    • Azienda Ospedaliero-Universitaria Ferrara
  • Milan, Italy, 20141
    • Istituto Europeo di Oncologia
  • Milan, Italy, 20133
    • Fondazione IRCCS Istituto Nazionale dei Tumori.
  • Naples, Italy, 80131
    • Universita della Campania Luigi Vanvitelli
  • Napoli, Italy, 80131
    • Istituto Nazionale Tumori IRCCS Fondazione G Pascale
  • Novara, Italy, 28100
    • Azienda Ospedaliero-Universitaria Maggiore della Carita - Oncology
  • Pisa, Italy, 56126
    • U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero Universitaria Pisana
  • Rome, Italy, 00128
    • Campus Bio-Medico di Roma
  • Taormina, Italy, 98039
    • Medical oncology
  • Udine, Italy, 33100
    • Azienda Sanitaria Universitaria del Friuli Centrale
• Spain
  • Barcelona, Spain, 08036
    • Hospital Clinic De Barcelona
  • Barcelona, Spain, 08029
    • Vall d'Hebron Hospital
  • Granada, Spain, 18016
    • Hospital Clinico Universitario San Cecilio
  • Madrid, Spain, 28007
    • Hospital General Universitario Gregorio Marañón
  • Salamanca, Spain, 37007
    • Hospital Clinico Universitario de Salamanca
  • Valencia, Spain, 46009
    • Instituto Valenciano de Oncologia
  • Andalusia
    • Granada, Andalusia, Spain, 18015
      • Hospital Universitario Virgen De Las Nieves
    • Málaga, Andalusia, Spain, 29010
      • Hospital Universitario Virgen De La Victoria Malaga
  • Balearic Islands
    • Palma, Balearic Islands, Spain, 07120
      • Hospital Universitari Son Espases
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Germans Trias I Pujol
  • Catalonia
    • Barcelona, Catalonia, Spain, 08028
      • Instituto Oncologico Dr Rosell
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Hospital Clinico Universitario Virgen de La Arrixaca
  • Principality of Asturias
    • Oviedo, Principality of Asturias, Spain, 33011
      • Hospital Universitario Central de Asturias
• United States
  • California
    • La Jolla, California, United States, 92093
      • UC San Diego
    • Los Angeles, California, United States, 90089
      • Usc Norris Comprehensive Cancer Center
    • Newport Beach, California, United States, 92663
      • Hoag Family Cancer Institute
    • San Francisco, California, United States, 94143
      • University of California San Francisco (UCSF)
    • San Francisco, California, United States, 94115
      • California Pacific Medical Center Research Institute
    • Santa Monica, California, United States, 90404
      • St John's Cancer Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Connecticut
    • Hartford, Connecticut, United States, 06102
      • Hartford Hospital
    • New Haven, Connecticut, United States, 06510
      • Yale University Cancer Center
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory Healthcare, Emory Clinic
  • Illinois
    • Evanston, Illinois, United States, 60201
      • Northshore University Healthsystem
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute Brookline Avenue
    • Worcester, Massachusetts, United States, 01655
      • University of Massachusetts Chan Medical School
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • New Jersey
    • New Brunswick, New Jersey, United States, 08901
      • Rutgers Cancer Institute of New Jersey
  • New York
    • Lake Success, New York, United States, 11042
      • Northwell Health Cancer Institute
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke Cancer Institute, University Hospital
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Foundation
    • Cleveland, Ohio, United States, 44106
      • Seidman Cancer Center
    • Columbus, Ohio, United States, 43210
      • The Ohio State University James Comprehensive Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University Hospital
    • Pittsburgh, Pennsylvania, United States, 15232
      • University of Pittsburgh
  • Tennessee
    • Knoxville, Tennessee, United States, 37920
      • University of Tennessee Medical Center
  • Texas
    • Dallas, Texas, United States, 75235
      • UT Southwestern/Simmons Comprehensive Cancer Center
    • Houston, Texas, United States, 77030
      • University of Texas MD Anderson Cancer Center
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • University of Virginia
    • Fairfax, Virginia, United States, 22031
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key Inclusion Criteria:

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c) per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and have histologically confirmed cutaneous melanoma that is deemed completely surgically resectable in order to be eligible as described in the protocol.
2. Patients with stage III melanoma must have clinically detectable disease that is confirmed as malignant on the pathology report. The pathology report must be reviewed, signed and dated by the investigator; this process will be confirmed during the interactive voice response system (IVRS) process as described in the protocol.
3. Patients must be candidates for full resection with curative intent and must be able to be surgically rendered free of disease with negative margins on resected specimens at surgery. The treatment plan including date of surgery must be documented by the investigator prior to randomization.
4. All patients must undergo full disease staging through a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging must include a computer tomography (CT) scan of the chest, abdomen, pelvis (if the primary tumor is on the head/neck then include a CT scan of head/neck), and all known sites of previously resected disease (if applicable) and brain magnetic resonance imaging (MRI) (or brain CT with contrast allowed if MRI is contraindicated).
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Key Exclusion Criteria:

Medical conditions:

1. Primary uveal melanoma
2. Ongoing or recent (within 2 years) evidence of an autoimmune disease that required systemic treatment with immunosuppressive agents. The following are non-exclusionary: vitiligo, childhood asthma that has resolved, residual hypothyroidism that requires only hormone replacement, psoriasis not requiring systemic treatment.
3. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion or, if given to a target lesion, there is pathological evidence of disease progression in the same lesion.

4. 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 as described in the protocol.

   Prior/concomitant therapy:

5. Use of immunosuppressive doses of corticosteroids (≥10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication as described in the protocol.

6. Treatment with any anti-cancer therapy for malignancies other than melanoma, including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol.

   Other comorbidities:

7. Participants with a history of myocarditis.
8. History or current evidence of significant (CTCAE grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 2 weeks prior to the first dose of trial medication.

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: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; As described in the protocol	Drug: Placebo; Administered per the protocol; Drug: cemiplimab; Administered per the protocol; Other Names: REGN2810; Libtayo
Experimental: Arm B; As described in the protocol	Drug: Fixed Dose Combination (FDC) cemiplimab+fianlimab; Or coadministration, depending on availability.; Other Names: REGN2810; Libtayo; REGN3767
Experimental: Arm C; As described in the protocol	Drug: Fixed Dose Combination (FDC) cemiplimab+fianlimab; Or coadministration, depending on availability.; Other Names: REGN2810; Libtayo; REGN3767

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete response (pCR) rate as assessed by Blinded Independent Pathological Review (BIPR)	Up to 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)		Up to 4 years
Overall survival (OS)		Up to 4 years
Distant metastasis-free survival (DMFS)		Up to 4 years
Major pathological response (MPR) as assessed by BIPR		Up to 4 years
Occurrence of treatment-emergent adverse events (TEAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of immune-mediated adverse events (imAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of serious adverse events (SAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of adverse events of special interest (AESIs)		90 days following last dose of study drug, approximately 4 years
Occurrence of TEAEs resulting in death		90 days following last dose of study drug, approximately 4 years
Occurrence of interruption or discontinuation of study drug(s) due to TEAE.		90 days following last dose of study drug, approximately 4 years
Occurrence of cancellation of surgery due to TEAE or delay to surgery		90 days following last dose of study drug, approximately 4 years
Concentrations of fianlimab in serum		Up to 4 years
Concentrations of cemiplimab in serum		Up to 4 years
Anti-drug antibodies (ADA) in serum to fianlimab		Up to 4 years
ADA in serum to cemiplimab		Up to 4 years
Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30)	EORTC-QLQ-C30 is a 30-item subject self-report questionnaire composed of both multi-item and single scales, including a global health status/quality of life (GHS/QoL) scale. Participants rate items on a four-point scale, with 1 as "not at all" and 4 as "very much." A change of 5 - 10 points is considered a small change. A change of 10 - 20 points is considered a moderate change.	Up to 4 years
Change from baseline in global health status/QoL per EORTC QLQ-C30		Up to 4 years
Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L)	The EQ-5D-5L consists of EQ-5D descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Up to 4 years
pCR rate as assessed by local pathologic review		Up to 1 year
Event-Free Survival (EFS)		Up to 4 years
MPR rate as assessed by local pathologic review		Up to 4 years
Objective Response Rate (ORR) assessed by investigator per RECIST 1.1 criteria		Up to 4 years
ORR assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 criteria		Up to 4 years
Occurrence of laboratory abnormalities	Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	90 days following last dose of study drug, approximately 4 years
Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale	The FACT-M is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACT-M is scored on a 5-point Likert-scale: "Not at all", "A little bit", "Somewhat", "Quite a bit", and "Very much.". A Higher score represents higher Health Related Quality of Life (HRQoL).	Up to 4 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2024
• Primary Completion (Estimated): November 2, 2026
• Study Completion (Estimated): December 9, 2030

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): February 10, 2026
• Last Update Submitted That Met QC Criteria: February 9, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Skin cancer; Fully resectable stage III melanoma; Fully resectable stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Skin Diseases; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Skin and Connective Tissue Diseases; Melanoma; Skin Neoplasms; Substandard Drugs; Pharmaceutical Preparations; cemiplimab
• Other Study ID Numbers: R3767-ONC-2208; 2022-502825-17-00 (Ctis: EU CT)

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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• 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