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
- Conditions
- Melanoma
- Interventions
- Registration Number
- NCT06190951
- Lead Sponsor
- Regeneron Pharmaceuticals
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 150
- 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.
- 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.
- 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.
- 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).
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
Key
Medical conditions:
-
Primary uveal melanoma
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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.
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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.
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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:
-
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.
-
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:
-
Participants with a history of myocarditis.
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm A cemiplimab As described in the protocol Arm A Placebo As described in the protocol Arm B Fixed Dose Combination (FDC) cemiplimab+fianlimab As described in the protocol Arm C Fixed Dose Combination (FDC) cemiplimab+fianlimab As described in the protocol
- Primary Outcome Measures
Name Time Method Pathological complete response (pCR) rate as assessed by Blinded Independent Pathological Review (BIPR) Up to 1 year
- Secondary Outcome Measures
Name Time Method Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L) Up to 4 years 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.
pCR rate as assessed by local pathologic review Up to 1 year Event-Free Survival (EFS) Up to 4 years Distant metastasis-free survival (DMFS) Up to 4 years Overall survival (OS) Up to 4 years Major pathological response (MPR) as assessed by BIPR 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 Relapse-free survival (RFS) 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 Occurrence of laboratory abnormalities 90 days following last dose of study drug, approximately 4 years Grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
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 disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale Up to 4 years 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).
Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30) Up to 4 years 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.
Change from baseline in global health status/QoL per EORTC QLQ-C30 Up to 4 years
Trial Locations
- Locations (45)
UC San Diego
🇺🇸La Jolla, California, United States
USC Norris Comprehensive Cancer Center
🇺🇸Los Angeles, California, United States
Hoag Family Cancer Institute
🇺🇸Newport Beach, California, United States
California Pacific Medical Center Research Institute
🇺🇸San Francisco, California, United States
University of California San Francisco (UCSF)
🇺🇸San Francisco, California, United States
St John's Cancer Institute
🇺🇸Santa Monica, California, United States
Hartford Hospital
🇺🇸Hartford, Connecticut, United States
Emory Healthcare, Emory Clinic
🇺🇸Atlanta, Georgia, United States
NorthShore University HealthSystem
🇺🇸Evanston, Illinois, United States
University of Massachusetts Chan Medical School
🇺🇸Worcester, Massachusetts, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Rutgers Cancer Institute of New Jersey
🇺🇸New Brunswick, New Jersey, United States
Northwell Health Cancer Institute
🇺🇸Lake Success, New York, United States
Duke Cancer Institute, University Hospital
🇺🇸Durham, North Carolina, United States
Seidman Cancer Center
🇺🇸Cleveland, Ohio, United States
Cleveland Clinic Foundation
🇺🇸Cleveland, Ohio, United States
Thomas Jefferson University Hospital
🇺🇸Philadelphia, Pennsylvania, United States
University of Tennessee Medical Center
🇺🇸Knoxville, Tennessee, United States
Hospital Clinico Universitario de Salamanca
🇪🇸Salamanca, Spain
University of Texas MD Anderson Cancer Center
🇺🇸Houston, Texas, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Westmead Hospital
🇦🇺Westmead, New South Wales, Australia
Melanoma Institute of Australia
🇦🇺Wollstonecraft, New South Wales, Australia
The Queen Elizabeth Hospital
🇦🇺Woodville, South Australia, Australia
Peter MacCallum Cancer Centre
🇦🇺Melbourne, Victoria, Australia
One Clinical Research at Hollywood Private Hospital
🇦🇺Nedlands, Western Australia, Australia
Centre Hospitalier de l'Universite de Montreal (CHUM)
🇨🇦Montreal, Quebec, Canada
CHU de Quebec - Universite Laval
🇨🇦Quebec City, Quebec, Canada
CHU-Dijon
🇫🇷Dijon, Burgundy, France
Chu De Bordeaux
🇫🇷Bordeaux, Gironde, France
Saint Louis Hospital
🇫🇷Paris, Ile De France, France
Gustave Roussy
🇫🇷Villejuif, Ile De France, France
Centre Francois Baclesse
🇫🇷Caen, Normandy, France
Hopital Ambroise Pare
🇫🇷Boulogne, France
CHU Estaing
🇫🇷Clermont Ferrand, France
Regional University Hospital of Lille 2208
🇫🇷Lille, France
Hopital Timone
🇫🇷Marseille, France
Centre Hospitalier Universitaire De Nice Hopital De L Archet
🇫🇷Nice, France
University Hospital Giessen
🇩🇪Giessen, Hessen, Germany
Universitatsklinikum Leipzig, AoR
🇩🇪Leipzig, Saxony, Germany
Charite University Medicine
🇩🇪Berlin, Germany
Azienda Ospedaliero-Universitaria Ferrara
🇮🇹Cona, Ferrara, Italy
U.O. Oncologia Medica 2 Universitaria, Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Italy
Vall d'Hebron Hospital
🇪🇸Barcelona, Spain
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain