Clinical Study of Fianlimab in Combination With Cemiplimab in Adolescent and Adult Patients With Previously Untreated Unresectable Locally Advanced or Metastatic Melanoma
Study Details
Study Description
Brief Summary
The primary objective of the study is to demonstrate superiority of fianlimab + cemiplimab compared to pembrolizumab, as measured by progression-free survival (PFS)
The secondary objectives of the study are:
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To demonstrate superiority of fianlimab (REGN3767) + cemiplimab compared to pembrolizumab, as measured by overall survival (OS)
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To demonstrate superiority in objective response rate (ORR) with fianlimab + cemiplimab compared to pembrolizumab
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To characterize ORR, PFS, and OS with fianlimab + cemiplimab compared to cemiplimab to inform the contribution of each component
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To assess immunogenicity of fianlimab and cemiplimab
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To assess impact of fianlimab + cemiplimab on physical functioning and role functioning and global health status/quality of life, as compared to pembrolizumab in adults
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To characterize safety and tolerability of treatment in patients 12 to <18 years of age
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To characterize ORR, PFS, and OS with treatment in patients 12 to <18 years of age
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To assess the safety and tolerability of fianlimab + cemiplimab compared to pembrolizumab and to cemiplimab
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To characterize pharmacokinetics (PK) of fianlimab and cemiplimab using sparse PK sampling in patients aged ≥12 years
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: A: fianlimab+cemiplimab The first 800 adult patients will be randomized in a 2:1:1 ratio to Arm A, Arm B, or Arm C; the next approximately 300 patients will be randomized in a 2:1 ratio to Arm A or Arm B |
Drug: Fianlimab
Intravenous (IV) infusion
Other Names:
Drug: Cemiplimab
IV infusion
Other Names:
|
| Experimental: B: pembrolizumab+placebo The first 800 adult patients will be randomized in a 2:1:1 ratio to Arm A, Arm B, or Arm C; the next approximately 300 patients will be randomized in a 2:1 ratio to Arm A or Arm B |
Drug: Pembrolizumab
IV infusion
Other Names:
Drug: Placebo
IV infusion
|
| Experimental: C: cemiplimab+placebo The first 800 adult patients will be randomized in a 2:1:1 ratio to Arm A, Arm B, or Arm C; the next approximately 300 patients will be randomized in a 2:1 ratio to Arm A or Arm B |
Drug: Cemiplimab
IV infusion
Other Names:
Drug: Placebo
IV infusion
|
Outcome Measures
Primary Outcome Measures
- 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
- 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 and immune RECIST (iRECIST)
- 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 and immune RECIST (iRECIST)
- Duration of response (DoR) [Up to 27 months]
per RECIST 1.1 via BICR or based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- PFS [Up to 27 months]
Based on investigator assessment according to RECIST 1.1 and immune RECIST (iRECIST)
- 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-related adverse event (irAEs)
- 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 irAEs
- Incidence of deaths [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 (FACT)-melanoma (melanoma subscale only) [Up to 90 days post last dose, approximately 6 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).
- 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 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.
- Change in role functioning per EORTC QLQ-C30 [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.
- 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 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 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.
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Age ≥12 years on the date of providing informed consent
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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
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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 irAEs ≥ 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.
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Patients with acral and mucosal melanomas are eligible. Accrual will be limited to 10% of the total population.
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Measurable disease per RECIST v1.1
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Previously irradiated lesions can only be counted as target lesions if they have been demonstrated to progress and no other target lesion is available
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Cutaneous lesions should be evaluated as non-target lesions
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Performance status:
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For adult patients: Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1
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For pediatric patients: Karnofsky performance status ≥70 (patients ≥16 years) or Lansky performance status ≥70 (patients ≤16 years)
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Anticipated life expectancy of at least 3 months
Key Exclusion Criteria:
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Uveal melanoma
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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.
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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
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Unknown BRAF V600 mutation status
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Systemic immune suppression:
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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.
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Other clinically relevant forms of systemic immune suppression
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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.
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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.
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Active or untreated brain metastases or spinal cord compression. Patients with leptomeningeal disease are excluded. Patients with known brain metastases are eligible if they:
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Received radiotherapy or another appropriate standard therapy for the brain metastases,
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Have neurologically returned to baseline (except for residual signs and symptoms related to the CNS treatment) for at least 14 days prior to enrollment
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Did not require immunosuppressive doses of corticosteroids therapy (>10mg of prednisone per day or equivalent) in the 14 days prior to enrollment
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Are asymptomatic with a single untreated brain metastasis < 10 mm in size
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Adolescent patients (≥12 to <18 years old) with body weight <40 kg
Note: Other protocol-defined Inclusion/ Exclusion criteria apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Orlando Health, Inc | Orlando | Florida | United States | 32806 |
| 2 | University of Tennessee Medical Center | Knoxville | Tennessee | United States | 37920 |
Sponsors and Collaborators
- Regeneron Pharmaceuticals
Investigators
- Study Director: Clinical Trial Management, Regeneron Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- R3767-ONC-2011
- 2021-004453-23