Melanoma
Conditions
Keywords
Resected High Risk Melanoma, Skin Cancer, Stage IIB, Stage IIC, Stage III, Stage IV, LAG-3 Lymphocyte activation gene 3, Adjuvant Setting, anti-PD-1 Monoclonal Antibody
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 an approved medication called pembrolizumab. The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to pembrolizumab in patients that have had melanoma removal surgery but are still at high risk for the recurrence of the disease. Pembrolizumab is an approved treatment in some countries in this clinical setting. The study is looking at several other research questions, including: * What side effects may happen from receiving the study drugs. * How much study drug is in the blood at different times. * Whether the body makes antibodies against the study drug (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
DRUGFianlimab
Fianlimab will be administered by intravenous (IV) infusion every (Q) 3 weeks
DRUGCemiplimab
Cemiplimab will be administered by IV infusion Q 3 weeks
DRUGPembrolizumab
Pembrolizumab will be administered by IV infusion Q 3 weeks
DRUGPlacebo
Matching placebo co-infused with pembrolizumab IV, will be administered by IV infusion Q 3 weeks
Sponsors
Regeneron Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. All patients must be either stage IIB, IIC, III, or stage IV per American Joint Committee on Cancer (AJCC) 8th edition and have histologically confirmed melanoma that is completely surgically resected in order to be eligible as defined by the protocol 2. Complete surgical resection must be performed within 12 weeks prior to randomization, and enrollment may occur only after satisfactory wound healing from the surgery 3. All patients must have disease-free status documented by a complete physical examination and imaging studies within 4 weeks prior to randomization, as described in the protocol Key
Exclusion criteria
1. Uveal melanoma 2. Any evidence of residual disease after surgery by imaging, pathology, or cytology. 3. Ongoing or recent (within 2 years) evidence of clinically significant autoimmune disease that required treatment 4. Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or hepatitis C (HCV) infection; or diagnosis of immunodeficiency that is related to, or results in chronic infection, as described in the protocol 5. Another malignancy that is currently progressing or that required active treatment in the past 5 years, as described in the protocol 6. Participants with a history of myocarditis 7. Adolescent patients (≥12 to \<18 years old) with body weight \<40 kg Note: Other Protocol Defined Inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relapse free survival (RSF) | Up to 5 Years | Time from randomization to the first documented recurrence of disease at any site (excluding new primary melanomas) or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Distant metastasis-free survival (DMFS) | Up to 5 Years | Time between the date of randomization and the date of the first distant metastasis. |
| Overall survival (OS) | Up to 5 Years | Time from randomization to the date of death. |
| Occurrence of treatment-emergent adverse events (TEAEs) | Up to 5 Years | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Occurrence of immune-mediated EAEs (im-EAEs) | Up to 5 Years | imAEs are a unique set of toxicities thought to be caused by unrestrained cellular immune responses. |
| Occurrence of serious adverse events (SAEs) | Up to 5 Years | An SAE is any untoward medical occurrence that at any dose: * Results in death - includes all deaths, even those that appear to be completely unrelated to study drug (eg, a car accident in which a patient is a passenger). * Is life-threatening * Requires in-patient hospitalization or prolongation of existing hospitalization. * Results in persistent or significant disability/incapacity * Is a congenital anomaly/birth defect. * Is an important medical event |
| Occurrence of adverse events of special interest (AESIs) | Up to 5 Years | An AESI (serious or non-serious) is one of scientific and medical concern specific to the sponsor's product or program, for which ongoing monitoring and rapid communication by the Investigator to the sponsor can be appropriate. Such an event might warrant further investigation in order to characterize and understand it |
| Occurrence of TEAEs resulting in death | Up to 5 Years | A TEAE resulting in death is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Occurrence of dose-limiting toxicity (DLT) | Up to 5 Years | A DLT is defined as a study-drug related TEAE, including imAEs, that could preclude enrolling additional adolescent patients at the selected dose. Dose-limiting toxicity will be evaluated in adolescents only. |
| Occurrence of interruption or discontinuation of study drug(s) due to TEAE | Up to 5 Years | A TEAE is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. |
| Occurrence of laboratory abnormalities | Up to 5 Years | As assessed by the NCI-CTCAE grading system (≥ Grade 3 or higher) |
| Concentrations of fianlimab in serum over time | Up to 5 Years | The concentrations of fianlimab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients. |
| Concentrations of cemiplimab in serum over time | Up to 5 Years | The concentrations of cemiplimab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients. |
| Concentration of finalimab anti-drug antibodies (ADA) and neutralizing antibodies | Up to 5 Years | Immunogenicity will be characterized per drug molecule by ADA and NAb status. |
| Concentration of cemiplimab anti-drug antibodies (ADA) and neutralizing antibodies | Up to 5 Years | Immunogenicity will be characterized per drug molecule by ADA and NAb status. |
| Patient report outcomes (PRO) for adults as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC-QLQ-C30) | Up to 5 Year | The EORTC QLQ-C30 (Version 3) uses for the questions 1 to 28 a 4-point scale. The scale scores from 1 to 4: 1 ("Not at all"), 2 ("A little"), 3 ("Quite a bit") and 4 ("Very much"). Half points are not allowed. The range is 3. For the raw score, less points are considered to have a better outcome. The EORTC QLQ-C30 (Version 3) uses for the questions 29 and 30 a 7-points scale. The scale scores from 1 to 7: 1 ("very poor") to 7 ("excellent"). Half points are not allowed. The range is 6. More points are considered to have a better outcome. |
| PRO for adults as measured by the European Quality of Life Dimension 5 (EQ-5D-5L) | Up to 5 Years | The EQ-5D-5L a descriptive system that 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. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. This decision results in a 1-digit number that expresses the level selected for that dimension. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state. |
| PRO for adults as measured by the Functional Assessment of Cancer Therapy (FACT) - melanoma | Up to 5 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). |
| PRO for adults as determined by the Patient Global Impressions Scale (PGIS) | Up to 5 Years | The PGIS is a single 1-item questionnaire designed to assess participant's overall impression of disease severity at a given point in time by using a 4-point Likert scale that ranges from (1) = "none (no symptoms)" to (4) = "severe". |
| PRO for adults as determined by the Patient Global Impressions of Change Scale (PGIC) | Up to 5 Years | The PGIC is a single-item questionnaire designed to assess the participant's overall sense of whether there has been a change since starting treatment as rated on a 5-point Likert scale anchored by (1) "much better" to (5) "much worse", with (4) = "no change". |
| Time to global health status/quality of life deterioration per EORTC QLQ-C30 | Up to 5 years | — |
| Time to physical functioning deterioration per EORTC QLQ-C30 | Up to 5 Years | — |
| Time to role functioning deterioration per EORTC QLQ-C30 | Up to 5 Years | — |
Countries
Argentina, Australia, Belgium, Brazil, Canada, Chile, Czechia, France, Georgia, Germany, Greece, Ireland, Israel, Italy, Mexico, Poland, Romania, South Africa, Spain, Turkey (Türkiye), United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trial Management
Regeneron Pharmaceuticals
Outcome results
None listed