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

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3

Conditions: Melanoma

Treatments: Drug: Cemiplimab; Drug: Placebo; Drug: Fianlimab; Drug: Pembrolizumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05352672

2021-004453-23 (EudraCT Number)

R3767-ONC-2011

2023-505772-30-00 (Registry Identifier)

Details and patient eligibility

About

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

Enrollment: 1,535 estimated patients

Sex: All

Ages: 12+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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1,535 participants in 4 patient groups

A: fianlimab+cemiplimab dose 1

Experimental group

Description:

As defined in Protocol Amendment 5

Treatment:

Drug: Fianlimab

Drug: Cemiplimab

A1: fianlimab+cemiplimab dose 2

Experimental group

Description:

As defined in Protocol Amendment 5

Treatment:

Drug: Fianlimab

Drug: Cemiplimab

B: pembrolizumab+placebo

Experimental group

Description:

As defined in Protocol Amendment 5

Treatment:

Drug: Pembrolizumab

Drug: Placebo

C: cemiplimab+placebo

Experimental group

Description:

As defined in Protocol Amendment 5

Treatment:

Drug: Placebo

Drug: Cemiplimab