Melanoma
Conditions
Keywords
Skin cancer, Fully resectable stage III melanoma, Fully resectable stage IV melanoma
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.
Interventions
DRUGcemiplimab
Administered per the protocol
DRUGFixed Dose Combination (FDC) cemiplimab+fianlimab
Or coadministration, depending on availability.
DRUGPlacebo
Administered per the protocol
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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/
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response (pCR) rate as assessed by Blinded Independent Pathological Review (BIPR) | Up to 1 year |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| 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. |
Countries
Australia, Austria, Canada, France, Germany, Italy, Spain, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed