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

A Phase 2 Peri-operative Trial of Fianlimab and Cemiplimab Compared With Pembrolizumab in Patients With Resectable Stage III and IV Melanoma

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 drug 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 drugs.
• How much study drug is in your blood at different times.
• Whether the body makes antibodies against the study drug (which could make the drug less effective or could lead to side effects). Antibodies are proteins that are naturally found in your blood stream that fight infections.
• How administering the study drugs might improve your quality of life.

Study Overview

• Status: Not yet recruiting
• Conditions: Melanoma
• Intervention / Treatment: Drug: cemiplimab; Drug: Placebo; Drug: pembrolizumab; Drug: fianlimab HD; Drug: fianlimab LD

• Study Type: Interventional
• Enrollment (Estimated): 360
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Clinical Trials Administrator; Phone Number: 844-734-6643; Email: clinicaltrials@regeneron.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 diagnostic quality computer tomography (CT) scan of the neck, chest, abdomen, pelvis 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. A patient must have an evaluable lymphocyte activation gene 3 (LAG-3) immunohistochemistry (IHC) result, centrally tested, to be enrolled into the study. Any LAG-3 level (0-100% expression) will be allowed as described in the protocol.
6. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A; Randomized 1:1:1	Drug: Placebo; Administered IV Q3W; Drug: pembrolizumab; Administered intravenous (IV) every 3 weeks (Q3W); Other Names: Keytruda; lambrolizumab; MK-3475
Experimental: Arm B; Randomized 1:1:1	Drug: cemiplimab; Administered IV Q3W; Other Names: REGN2810; Libtayo; Drug: fianlimab HD; Administered IV Q3W; Other Names: REGN3767
Experimental: Arm C; Randomized 1:1:1	Drug: cemiplimab; Administered IV Q3W; Other Names: REGN2810; Libtayo; Drug: fianlimab LD; Administered IV Q3W; Other Names: REGN3767

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pathological complete response (pCR) rate as assessed by blinded independent pathological review (BIPR)	33 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relapse-free survival (RFS)		Up to 4 years
Overall survival (OS)		Up to 4 years
Event-free survival (EFS)		57 months
Distant metastasis-free survival (DMFS)		Up to 4 years
Major pathological response (MPR) as assessed by BIPR		Up to 4 years
Pathological complete response (pCR) rate as assessed by local pathology review		Up to 4 years
Major pathological response (MPR) rate as assessed by local pathology review		Up to 4 years
Tumor response rate		Up to 3 years
Occurrence of treatment-emergent adverse events (TEAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of immune-mediated adverse events (imAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of serious adverse events (SAEs)		90 days following last dose of study drug, approximately 4 years
Occurrence of adverse events of special interest (AESIs)		90 days following last dose of study drug, approximately 4 years
Occurrence of TEAEs resulting in death		90 days following last dose of study drug, approximately 4 years
Occurrence of interruption or discontinuation of study drug(s) due to TEAE.		90 days following last dose of study drug, approximately 4 years
Occurrence of cancellation of surgery due to TEAE or delay to surgery		90 days following last dose of study drug, approximately 4 years
Occurrence of laboratory abnormalities	grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)	90 days following last dose of study drug, approximately 4 years
Concentrations of fianlimab in serum		Up to 4 years
Concentrations of cemiplimab in serum		Up to 4 years
Anti-drug antibodies (ADA) in serum to fianlimab		Up to 4 years
ADA in serum to cemiplimab		Up to 4 years
Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale	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).	Up to 4 years
Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30)	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.	Up to 4 years
Change from baseline in global health status/QoL per EORTC QLQ-C30		Up to 4 years
Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L)	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.	Up to 4 years

Collaborators and Investigators

• Sponsor: Regeneron Pharmaceuticals
• Investigators: Study Director: Clinical Trial Management, Regeneron Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Estimated): February 9, 2024
• Primary Completion (Estimated): December 23, 2030
• Study Completion (Estimated): December 23, 2030

Study Registration Dates

• First Submitted: November 9, 2023
• First Submitted That Met QC Criteria: December 19, 2023
• First Posted (Actual): January 5, 2024

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: December 19, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: Skin cancer; Fully resectable stage III melanoma; Fully resectable stage IV melanoma
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroendocrine Tumors; Nevi and Melanomas; Melanoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Pembrolizumab; Cemiplimab
• Other Study ID Numbers: R3767-ONC-2208; 2022-502825-17-00 (Registry Identifier: EU CT)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• IPD Sharing Time Frame: When Regeneron has received marketing authorization from major health authorities (e.g., FDA, European Medicines Agency (EMA), Pharmaceuticals and Medical Devices Agency (PMDA), etc.) for the product and indication, has made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry), has the legal authority to share the data, and has ensured the ability to protect participant privacy.
• IPD Sharing Access Criteria: Qualified researchers can submit a proposal for access to individual patient or aggregate level data from a Regeneron-sponsored clinical trial through Vivli. Regeneron's Independent Research Request Evaluation Criteria can be found at: https://www.regeneron.com/sites/default/files/Regeneron-External-Data-Sharing-Policy-and-Independent-Research-Request-Evaluation-Criteria.pdf
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No