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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

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ClinicalTrials.gov Identifier: NCT05608291
Recruitment Status : Recruiting
First Posted : November 8, 2022
Last Update Posted : April 22, 2024
Sponsor:
Information provided by (Responsible Party):
Regeneron Pharmaceuticals

Study Description
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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.

Condition or disease Intervention/treatment Phase
Melanoma Drug: Fianlimab Drug: Cemiplimab Drug: Pembrolizumab Drug: Placebo Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1530 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : January 16, 2023
Estimated Primary Completion Date : May 16, 2028
Estimated Study Completion Date : February 15, 2030

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Melanoma
MedlinePlus related topics: Melanoma

Arms and Interventions
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Arm Intervention/treatment
Experimental: Fianlimab HD + Cemiplimab
Patients will be administered one combination dose of fianlimab high dose (HD) and cemiplimab
 Drug: Fianlimab
Fianlimab will be administered by intravenous (IV) infusion every (Q) 3 weeks
Other Name: REGN3767

Drug: Cemiplimab
Cemiplimab will be administered by IV infusion Q 3 weeks
Other Names:
  • REGN2810
  • Libtayo
Experimental: Fianlimab LD + Cemiplimab
Patients will be administered one combination dose of fianlimab low dose (LD) and cemiplimab
 Drug: Fianlimab
Fianlimab will be administered by intravenous (IV) infusion every (Q) 3 weeks
Other Name: REGN3767

Drug: Cemiplimab
Cemiplimab will be administered by IV infusion Q 3 weeks
Other Names:
  • REGN2810
  • Libtayo
Active Comparator: Pembrolizumab
Patients will be administered one dose of pembrolizumab co-infused with saline/dextrose placebo
 Drug: Pembrolizumab
Pembrolizumab will be administered by IV infusion Q 3 weeks
Other Names:
  • MK-3475
  • lambrolizumab
  • Keytruda

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


Outcome Measures
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Primary Outcome Measures :
  1. Relapse free survival (RSF) [ Time Frame: 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 Outcome Measures :
  1. Distant metastasis-free survival (DMFS) [ Time Frame: Up to 5 Years ]
    Time between the date of randomization and the date of the first distant metastasis.

  2. Overall survival (OS) [ Time Frame: Up to 5 Years ]
    Time from randomization to the date of death.

  3. Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: 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.

  4. Occurrence of immune-mediated EAEs (im-EAEs) [ Time Frame: Up to 5 Years ]
    imAEs are a unique set of toxicities thought to be caused by unrestrained cellular immune responses.

  5. Occurrence of serious adverse events (SAEs) [ Time Frame: 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

  6. Occurrence of adverse events of special interest (AESIs) [ Time Frame: 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

  7. Occurrence of TEAEs resulting in death [ Time Frame: 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.

  8. Occurrence of dose-limiting toxicity (DLT) [ Time Frame: 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.

  9. Occurrence of interruption or discontinuation of study drug(s) due to TEAE [ Time Frame: 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.

  10. Occurrence of laboratory abnormalities [ Time Frame: Up to 5 Years ]
    As assessed by the NCI-CTCAE grading system (≥ Grade 3 or higher)

  11. Concentrations of fianlimab in serum over time [ Time Frame: 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.

  12. Concentrations of cemiplimab in serum over time [ Time Frame: 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.

  13. Concentration of finalimab anti-drug antibodies (ADA) and neutralizing antibodies [ Time Frame: Up to 5 Years ]
    Immunogenicity will be characterized per drug molecule by ADA and NAb status.

  14. Concentration of cemiplimab anti-drug antibodies (ADA) and neutralizing antibodies [ Time Frame: Up to 5 Years ]
    Immunogenicity will be characterized per drug molecule by ADA and NAb status.

  15. 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) [ Time Frame: 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.


  16. PRO for adults as measured by the European Quality of Life Dimension 5 (EQ-5D-5L) [ Time Frame: 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.

  17. PRO for adults as measured by the Functional Assessment of Cancer Therapy (FACT) - melanoma [ Time Frame: 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).

  18. PRO for adults as determined by the Patient Global Impressions Scale (PGIS) [ Time Frame: 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".

  19. PRO for adults as determined by the Patient Global Impressions of Change Scale (PGIC) [ Time Frame: 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".

  20. Time to global health status/quality of life deterioration per EORTC QLQ-C30 [ Time Frame: Up to 5 years ]
  21. Time to physical functioning deterioration per EORTC QLQ-C30 [ Time Frame: Up to 5 Years ]
  22. Time to role functioning deterioration per EORTC QLQ-C30 [ Time Frame: Up to 5 Years ]

Eligibility Criteria
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Ages Eligible for Study:   12 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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/ Exclusion Criteria Apply

Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05608291


Contacts
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Contact: Clinical Trials Administrator 844-734-6643 clinicaltrials@regeneron.com

Locations
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Sponsors and Collaborators
Regeneron Pharmaceuticals
Investigators
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Study Director: Clinical Trial Management Regeneron Pharmaceuticals
More Information
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Additional Information:

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Responsible Party: Regeneron Pharmaceuticals
ClinicalTrials.gov Identifier: NCT05608291    
Other Study ID Numbers: R3767-ONC-2055
2022-501576-25-00 ( Registry Identifier: EUCT Number )
First Posted: November 8, 2022    Key Record Dates
Last Update Posted: April 22, 2024
Last Verified: April 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
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, has made results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
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
URL: https://vivli.org/

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Regeneron Pharmaceuticals:
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
Additional relevant MeSH terms:
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Melanoma
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Skin Neoplasms
 Neoplasms by Site
Skin Diseases
Pembrolizumab
Cemiplimab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action