Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma

NCT05352672
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Phase
Phase 3
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Recruitment status
Active, not recruiting
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Participants
1,546
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Lead sponsor
Regeneron Pharmaceuticals
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Start date
2022-07-14
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Number of sites
210
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Summary
This study is researching an experimental drug called REGN3767, also known as fianlimab (R3767), when combined with another medication called REGN2810, also known as cemiplimab (each individually called a "study drug" or called "study drugs" when combined). The study is focused on patients with a type of skin cancer known as melanoma. The aims of the study are to see how effective the combination of fianlimab and cemiplimab are in treating the melanoma skin cancer, in comparison with a medication, pembrolizumab, approved for the treatment of melanoma skin cancer in adults, and to observe any similarities, or differences, in how the study drugs work in adolescent participants compared with adult participants. 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 drugs (which could make the drugs 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
clinicaltrials.gov
Short title
Clinical Study of Fianlimab in Combination With Cemiplimab Versus Pembrolizumab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
clinicaltrials.gov
Official title
A Phase 3 Trial of Fianlimab (REGN3767, Anti-LAG-3) + Cemiplimab Versus Pembrolizumab in Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Active, not recruiting
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Phase
Phase 3
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Study type
Interventional
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Completion date
2031-09-16
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First posted
2022-04-29
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Registry last updated
2026-04-22
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Primary completion date
2026-03-12
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Start date
2022-07-14
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Actual participants
1,546
clinicaltrials.gov
Participants
1,546
clinicaltrials.gov
Participant count basis
Actual
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Protocol amendments
6
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Number of sites
210
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Regeneron Pharmaceuticals
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Source registry
ClinicalTrials.gov
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Registry ID
NCT05352672
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ClinicalTrials.gov ID
NCT05352672
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Registry record
Open registry record
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Allocation
Randomised
Model
Parallel groups
Purpose
Treatment
Masking
Quadruple masking
Masked roles
Participants, Care providers, Investigators, Outcome assessors
Sources for study design
clinicaltrials.gov

  1. Progression-free survival (PFS)

    Timeframe: Approximately 27 months

    Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR)

  1. Overall survival (OS)

    Timeframe: Up to 96 months

  2. Objective response rate (ORR)

    Timeframe: Up to 27 months

    Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR) or based on investigator assessment according to RECIST 1.1

  3. Disease control rate (DCR)

    Timeframe: Up to 27 months

    Per RECIST 1.1 based on BICR or based on investigator assessment according to RECIST 1.1

  4. Duration of response (DoR)

    Timeframe: Up to 27 months

    Per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1

  5. PFS

    Timeframe: Up to 27 months

    Based on investigator assessment according to RECIST 1.1

  6. Incidence of Adverse Events (AEs)

    Timeframe: Up to 90 days post last dose, approximately 6 years

    Including treatment emergent adverse events (TEAEs), serious adverse events (SAEs), adverse events of special interest (AESIs), and/ or immune-mediated adverse events (imAEs)

  7. Occurrence of interruption and discontinuation of study drug(s) due to AEs

    Timeframe: Up to 90 days post last dose, approximately 6 years

    Including TEAEs, AESIs, and/ or imAEs

  8. TEAEs leading to death

    Timeframe: Up to 6 years

  9. Incidence of laboratory abnormalities

    Timeframe: Up to 90 days post last dose, approximately 6 years

    Will be graded using the current version of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grading system (version 5.0)

  10. Concentrations of cemiplimab in serum

    Timeframe: Up to 90 days post last dose, approximately 6 years

  11. Concentrations of fianlimab in serum

    Timeframe: Up to 90 days post last dose, approximately 6 years

  12. Incidence of anti-drug antibodies (ADA) to fianlimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  13. Titer of anti-drug antibodies (ADA) to fianlimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  14. Incidence of ADA to cemiplimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  15. Titer of ADA to cemiplimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  16. Incidence of neutralizing antibodies (NAb) to fianlimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  17. Incidence of NAb to cemiplimab over time

    Timeframe: Up to 30 days post last dose, approximately 6 years

  18. Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)

    Timeframe: Up to 90 days post last dose, approximately 6 years

    EORTC-QLQ-C30 is a 30-item participant 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.

  19. PROs as measured by EQ-5D-5L

    Timeframe: Up to 90 days post last dose, approximately 6 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. Overall scores range from 0 to 1, with low scores representing a higher level of dysfunction.

  20. PROs as measured by Functional Assessment of Cancer Therapy melanoma (FACTM) (melanoma subscale only)

    Timeframe: Up to 90 days post last dose, approximately 6 years

    The FACTM is a melanoma-specific quality of life questionnaire that is composed of items from the Functional Assessment of Cancer Therapy-General (FACT-G). The FACTM 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).

  21. PROs as measured by Patient Global Impression of Severity (PGIS)

    Timeframe: Up to 21 days post last dose, approximately 6 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".

  22. PROs as measured by Patient Global Impression of Change (PGIC)

    Timeframe: Up to 21 days post last dose, approximately 6 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"

  23. Change in physical functioning per EORTC QLQ-C30

    Timeframe: Baseline to Week 25

    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.

  24. Change in role functioning per EORTC QLQ-C30

    Timeframe: Baseline to Week 25

    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.

  25. Change in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30

    Timeframe: Baseline to Week 25

    Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30). 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.

And 3 more, listed on the interactive page.

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Children, Adults, Older adults
Minimum age
12 Years
Healthy volunteers
No

Key Inclusion Criteria:

  1. Age ≥12 years on the date of providing informed consent

  2. Patients with histologically confirmed unresectable Stage III and Stage IV (metastatic) melanoma (AJCC, 8th revised edition) who have not received prior systemic therapy for advanced unresectable disease

    1. Patients who received adjuvant and/or neoadjuvant systemic therapies are eligible if they did not have evidence of progression or recurrence of disease and/or discontinued due to occurrence of unmanageable imAEs ≥ grade 3 (with the exclusion of endocrinopathies which are fully controlled by hormone replacement) while on such therapies. Also, patients must have had a treatment-free and disease-free interval of >6 months. Accrual of these patients is limited to approximately 10% of the total population enrolled.
    2. Patients with acral and mucosal melanomas are eligible. Accrual will be limited to 10% of the total population.

  3. Measurable disease per RECIST v1.1

    1. Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
    2. Cutaneous lesions should be evaluated as non-target lesions

  4. Performance status:

    1. For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
    2. For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)

  5. Anticipated life expectancy of at least 3 months

Key Exclusion Criteria:

  1. 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. 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

  4. Unknown BRAF V600 mutation status as described in the protocol

  5. Systemic immune suppression:

    1. Use of immunosuppressive doses of corticosteroids (>10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication. Physiologic replacement doses are allowed up to and including 10mg of prednisone/day or equivalent. Inhaled or topical steroids are permitted, if they are not for treatment of an autoimmune disorder.
    2. Other clinically relevant forms of systemic immune suppression

  6. Treatment with other anti-cancer therapy including immuno- therapy, chemotherapy, major surgery or biological therapy within 21 days prior to the first dose of trial treatment. Adjuvant hormonotherapy used for breast cancer or other hormone-sensitive cancers in long term remission is allowed.

  7. History or current evidence of significant (CTCAE Grade ≥2) local or systemic infection (e. g., cellulitis, pneumonia, septicemia) requiring systemic antibiotic treatment within 14 days prior to the first dose of trial medication.

  8. Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:

    1. Received radiotherapy or another appropriate standard therapy for the brain metastases,
    2. Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
    3. Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
    4. Are asymptomatic with a single untreated brain metastasis <10 mm in size

  9. Participants with a history of myocarditis.

Note: Other protocol-defined Inclusion/ Exclusion criteria apply

Sources for eligibility
clinicaltrials.gov

  • UC San DiegoLa Jolla, United States
  • The Angeles Clinic and Research InstituteLos Angeles, United States
  • Orlando HealthOrlando, United States
  • Seidman Cancer CenterCleveland, United States
  • University of Tennessee Medical CenterKnoxville, United States
  • DIABAID - Instituto de Asistencia Integral en DiabetesCiudad Autonoma de Buenos Aires, Argentina
  • Centro Medico AustralCiudad Autonoma de Buenos Aires, Argentina
  • Centro de Investigacion PergaminoPergamino, Argentina
  • Instituto de Oncologia de RosarioRosario, Argentina
  • Centro de Investigaciones Medicas y Desarrollo LC S.R.L. (LC Investigacion)Buenos Aires, Argentina
  • ExelsusSan Miguel de Tucumán, Argentina
  • Gold Coast Hospital and Health ServiceSouthport, Australia
  • Townsville University HospitalTownsville, Australia
  • Calvary North Adelaide HospitalNorth Adelaide, Australia
  • Icon Cancer Centre HobartHobart, Australia
  • Andrew Love Cancer CentreGeelong, Australia
  • Alfred HospitalMelbourne, Australia
  • University Hospital Saint PoeltenSankt Pölten, Austria
  • Medical University of GrazGraz, Austria
  • Medical University InnsbruckInnsbruck, Austria
  • Medical University ViennaVienna, Austria
  • AZ GroeningeKortrijk, Belgium
  • AZ NikolaasSint-Niklaas, Belgium
  • Cliniques Universitaires Saint-LucBrussels, Belgium
  • Centre Hospitalier Universitaire Universite Catholique de Louvain Namur Site Sainte ElisabethNamur, Belgium

And 185 more, listed on the interactive page.

Sources for sites
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  • 2023
  • 2023-505772-30-00
  • 2021-004453-23
Sources for references
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Related records

Drugs (3)

Lead sponsors (1)

Conditions (1)

Targets (2)