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

Phase 3

Recruiting

• Conditions: Melanoma
• Interventions: Drug: Fianlimab; Drug: Pembrolizumab; Drug: Cemiplimab; Drug: Placebo

• Registration Number: NCT05352672
• Lead Sponsor: Regeneron Pharmaceuticals

Brief 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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-04-06
• Study First Submitted QC: 2022-04-25
• Study First Posted: 2022-04-29
• Study Start: 2022-07-14
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-28
• Last Update Posted: 2024-10-30
• Primary Completion: 2025-06-30
• Study Completion: 2031-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1535

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
A: fianlimab+cemiplimab dose 1	Fianlimab	As defined in Protocol Amendment 5
A: fianlimab+cemiplimab dose 1	Cemiplimab	As defined in Protocol Amendment 5
A1: fianlimab+cemiplimab dose 2	Fianlimab	As defined in Protocol Amendment 5
A1: fianlimab+cemiplimab dose 2	Cemiplimab	As defined in Protocol Amendment 5
B: pembrolizumab+placebo	Pembrolizumab	As defined in Protocol Amendment 5
B: pembrolizumab+placebo	Placebo	As defined in Protocol Amendment 5
C: cemiplimab+placebo	Cemiplimab	As defined in Protocol Amendment 5
C: cemiplimab+placebo	Placebo	As defined in Protocol Amendment 5

Primary Outcome Measures

Name	Time	Method
Progression-free survival (PFS)	Approximately 27 months	Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 based on Blinded Independent Central Review (BICR)

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 96 months
Objective response rate (ORR)	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
Disease control rate (DCR)	Up to 27 months	Per RECIST 1.1 based on BICR or based on investigator assessment according to RECIST 1.1
Duration of response (DoR)	Up to 27 months	Per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1
PFS	Up to 27 months	Based on investigator assessment according to RECIST 1.1
Incidence of Adverse Events (AEs)	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)
Occurrence of interruption and discontinuation of study drug(s) due to AEs	Up to 90 days post last dose, approximately 6 years	Including TEAEs, AESIs, and/ or imAEs
TEAEs leading to death	Up to 6 years
Incidence of laboratory abnormalities	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)
Concentrations of cemiplimab in serum	Up to 90 days post last dose, approximately 6 years
Concentrations of fianlimab in serum	Up to 90 days post last dose, approximately 6 years
Incidence of anti-drug antibodies (ADA) to fianlimab over time	Up to 30 days post last dose, approximately 6 years
Titer of anti-drug antibodies (ADA) to fianlimab over time	Up to 30 days post last dose, approximately 6 years
Incidence of ADA to cemiplimab over time	Up to 30 days post last dose, approximately 6 years
Titer of ADA to cemiplimab over time	Up to 30 days post last dose, approximately 6 years
Incidence of neutralizing antibodies (NAb) to fianlimab over time	Up to 30 days post last dose, approximately 6 years
Incidence of NAb to cemiplimab over time	Up to 30 days post last dose, approximately 6 years
Patient-reported outcomes (PROs) as measured by European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 (EORTC QLQ-C30)	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.
PROs as measured by EQ-5D-5L	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.
PROs as measured by Functional Assessment of Cancer Therapy melanoma (FACTM) (melanoma subscale only)	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).
PROs as measured by Patient Global Impression of Severity (PGIS)	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".
PROs as measured by Patient Global Impression of Change (PGIC)	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"
Change in physical functioning per EORTC QLQ-C30	Baseline to end of study, approximately 6 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 in role functioning per EORTC QLQ-C30	Baseline to end of study, approximately 6 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 in global health status/quality of life (GHS/QoL) per EORTC QLQ-C30	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.
Change in GHS/QoL per EORTC QLQ-C30	Baseline to end of study, approximately 6 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.

Trial Locations

Locations (219)

University of California San Diego; 🇺🇸 La Jolla, California, United States

The Angeles Clinic and Research Institute; 🇺🇸 Los Angeles, California, United States

Miami Cancer Institute; 🇺🇸 Miami, Florida, United States

Orlando Health, Inc; 🇺🇸 Orlando, Florida, United States

Atlantic Health System - Morristown Medical Center; 🇺🇸 Morristown, New Jersey, United States

University Hospitals Seidmand Cancer Center; 🇺🇸 Cleveland, Ohio, United States

Cleveland Clinic Foundation; 🇺🇸 Cleveland, Ohio, United States

University of Tennessee Medical Center; 🇺🇸 Knoxville, Tennessee, United States

Fundacion Cenit para la Investigacion en Neurociencias; 🇦🇷 Buenos Aires, Argentina

DIABAID - Instituto de Asistencia Integral en Diabetes; 🇦🇷 Buenos Aires, Argentina

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