Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Skin Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neuroendocrine Tumor

Neuroepithelioma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Cemiplimab

Immunoglobulins

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Patients will be administered one combination dose of fianlimab high dose (HD) and cemiplimab

Patients will be administered one combination dose of fianlimab low dose (LD) and cemiplimab

Patients will be administered one dose of pembrolizumab co-infused with saline/dextrose placebo

Fianlimab will be administered by intravenous (IV) infusion every (Q) 3 weeks

Fianlimab

Cemiplimab will be administered by IV infusion Q 3 weeks

Pembrolizumab will be administered by IV infusion Q 3 weeks

Matching placebo co-infused with pembrolizumab IV, will be administered by IV infusion Q 3 weeks

Placebo

Clinical Trials Administrator

Clinical Trial Management

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.

A Trial to See if the Combination of Fianlimab With Cemiplimab Works Better Than Pembrolizumab for Preventing or Delaying Melanoma From Coming Back After it Has Been Removed With Surgery

A Phase 3 Trial of Fianlimab (Anti-LAG-3) and Cemiplimab Versus Pembrolizumab in the Adjuvant Setting in Patients With Completely Resected High-risk Melanoma

All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.

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.

Time between the date of randomization and the date of the first distant metastasis.

Time from randomization to the date of death.

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.

imAEs are a unique set of toxicities thought to be caused by unrestrained cellular immune responses.

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

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

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.

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.

As assessed by the NCI-CTCAE grading system (≥ Grade 3 or higher)

The concentrations of fianlimab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients.

The concentrations of cemiplimab over time will be summarized by descriptive statistics by study arm for the overall population and for adolescent patients.

Immunogenicity will be characterized per drug molecule by ADA and NAb status.

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.

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.

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).

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".

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".

Spots Global Cancer Trial Database for resected high risk melanoma