A Trial to Learn if Fianlimab and Cemiplimab Are Safe and Work Better Than Anti-PD1 Alone in Adult Participants With Resectable Stage 3 or 4 Melanoma

Regeneron Pharmaceuticals

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Melanoma

Treatments: Drug: pembrolizumab; Drug: cemiplimab; Drug: fianlimab; Drug: cemiplimab+fianlimab

Study type: Interventional

Funder types: Industry

Identifiers

NCT06190951

2022-502825-17-00 (Registry Identifier)

R3767-ONC-2208

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 cemiplimab (each individually called a "study drug" or called "study drugs" when combined) compared with an approved medication called pembrolizumab. These types of study drugs are collectively known as immune checkpoint inhibitors. The study is focused on participants with a type of skin cancer known as melanoma.

The objective of this study is to see if the combination of fianlimab and cemiplimab is an effective treatment compared to pembrolizumab as peri-operative therapy in participants with high-risk melanoma.

The study is looking at several other research questions, including:

• What side effects may happen from receiving the study drug(s).
• How much study drug(s) is in the blood at different times.
• Whether the body makes antibodies against the study drug(s) (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.

Enrollment: 520 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

1. All patients must be either stage III (IIIB, IIIC, IIID) or stage IV (M1a, M1b, M1c) per American Joint Committee on Cancer (AJCC) 8th edition (Amin 2017) and have histologically confirmed cutaneous melanoma that is deemed completely surgically resectable in order to be eligible as described in the protocol.
2. Patients with stage III melanoma must have clinically detectable disease that is confirmed as malignant on the pathology report. The pathology report must be reviewed, signed and dated by the investigator; this process will be confirmed during the interactive voice response system (IVRS) process as described in the protocol.
3. Patients must be candidates for full resection with curative intent and must be able to be surgically rendered free of disease with negative margins on resected specimens at surgery. The treatment plan including date of surgery must be documented by the investigator prior to randomization.
4. All patients must undergo full disease staging through a complete physical examination and imaging studies within 4 weeks prior to randomization. Imaging must include a computer tomography (CT) scan of the chest, abdomen, pelvis (if the primary tumor is on the head/neck then include a CT scan of head/neck), and all known sites of previously resected disease (if applicable) and brain magnetic resonance imaging (MRI) (or brain CT with contrast allowed if MRI is contraindicated).
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1

Key Exclusion Criteria:

Medical conditions:

1. Primary 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. Patients must not have received any prior systemic anti-cancer therapy for melanoma. Prior radiotherapy for melanoma is allowed if not given to a target lesion or, if given to a target lesion, there is pathological evidence of disease progression in the same lesion.

4. 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 as described in the protocol.

   Prior/concomitant therapy:

5. Use of immunosuppressive doses of corticosteroids (>=10mg of prednisone per day or equivalent) within 14 days of the first dose of study medication as described in the protocol.

6. Treatment with any anti-cancer therapy for malignancies other than melanoma, including immuno- therapy, chemotherapy, radiotherapy, or biological therapy in the 5 years prior to randomization as described in the protocol.

   Other comorbidities:

7. Participants with a history of myocarditis.

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

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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520 participants in 4 patient groups

cemiplimab

Active Comparator group

Description:

Phase 2 Randomized 1:1:1

Treatment:

Drug: cemiplimab

cemiplimab+fianlimab HD

Experimental group

Description:

Phase 2 fianlimab HD Randomized 1:1:1 Phase 3 fianlimab ((if HD chosen for phase 3) Randomized 1:1

Treatment:

Drug: cemiplimab+fianlimab

Drug: fianlimab

cemiplimab+fianlimab LD

Experimental group

Description:

Phase 2 fianlimab LD Randomized 1:1:1 Phase 3 fianlimab (if LD chosen for Phase 3) Randomized 1:1

Treatment:

Drug: cemiplimab+fianlimab

Drug: fianlimab

pembrolizumab

Active Comparator group

Description:

Phase 3 Randomized 1:1

Treatment:

Drug: pembrolizumab