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

• ClinicalTrials.gov Identifier: NCT06190951
• Recruitment Status: Not yet recruiting
• First Posted: January 5, 2024
• Last Update Posted: May 15, 2024
• Sponsor: Regeneron Pharmaceuticals
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Melanoma	Drug: pembrolizumab; Drug: fianlimab; Drug: cemiplimab; Drug: cemiplimab+fianlimab	Phase 2; Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 520 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Phase 2 and Phase 3 Peri-operative Trial of Fianlimab and Cemiplimab Compared With Anti-PD1 Alone in Patients With Resectable Stage III and IV Melanoma
• Estimated Study Start Date: July 12, 2024
• Estimated Primary Completion Date: September 21, 2028
• Estimated Study Completion Date: June 4, 2033

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: cemiplimab; Phase 2 Randomized 1:1:1	Drug: cemiplimab; Administered IV Q3W Phase 2 Active Comparator; Other Names: REGN2810; Libtayo
Experimental: cemiplimab+fianlimab HD; Phase 2 fianlimab HD Randomized 1:1:1 Phase 3 fianlimab ((if HD chosen for phase 3) Randomized 1:1	Drug: fianlimab; Administered IV Q3W Phase 2; Other Name: REGN3767; Drug: cemiplimab+fianlimab; Administered IV Q3W Phase 3 Either fianlimab HD or fianlimab LD in combination with cemiplimab will be chosen for Phase 3; Other Names: REGN2810; Libtayo; REGN3767
Experimental: cemiplimab+fianlimab LD; Phase 2 fianlimab LD Randomized 1:1:1 Phase 3 fianlimab (if LD chosen for Phase 3) Randomized 1:1	Drug: fianlimab; Administered IV Q3W Phase 2; Other Name: REGN3767; Drug: cemiplimab+fianlimab; Administered IV Q3W Phase 3 Either fianlimab HD or fianlimab LD in combination with cemiplimab will be chosen for Phase 3; Other Names: REGN2810; Libtayo; REGN3767
Active Comparator: pembrolizumab; Phase 3 Randomized 1:1	Drug: pembrolizumab; Administered intravenous (IV) every 3 weeks (Q3W) Phase 3 active comparator; Other Names: MK-3475; lambrolizumab; Keytruda; Anti-PD1

Outcome Measures

Primary Outcome Measures :

1. Pathological complete response (pCR) rate as assessed by local pathological review [ Time Frame: Up to 1 year ]
   Phase 2
2. Event-free survival (EFS) [ Time Frame: Up to 4 years ]
   Phase 3

Secondary Outcome Measures :

1. pCR rate as assessed by Blinded Independent Pathological Review (BIPR) [ Time Frame: Up to 1 year ]
   Phase 2 and Phase 3
2. pCR rate as assessed by local pathological review [ Time Frame: Up to 1 year ]
   Phase 3
3. EFS [ Time Frame: Up to 4 years ]
   Phase 2
4. Distant metastasis-free survival (DMFS) [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
5. Overall survival (OS) [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
6. Major pathological response (MPR) as assessed by BIPR [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
7. MPR rate as assessed by local pathological review [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
8. ORR assessed by investigator per RECIST 1.1 criteria [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
9. ORR assessed by Blinded Independent Central Review (BICR) per RECIST 1.1 criteria [ Time Frame: Up to 4 years ]
   Phase 2 and Phase 3
10. Relapse-free survival (RFS) [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
11. Occurrence of treatment-emergent adverse events (TEAEs) [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
12. Occurrence of immune-mediated adverse events (imAEs) [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
13. Occurrence of serious adverse events (SAEs) [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
14. Occurrence of adverse events of special interest (AESIs) [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
15. Occurrence of TEAEs resulting in death [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
16. Occurrence of interruption or discontinuation of study drug(s) due to TEAE. [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
17. Occurrence of cancellation of surgery due to TEAE or delay to surgery [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3
18. Occurrence of laboratory abnormalities [ Time Frame: 90 days following last dose of study drug, approximately 4 years ]
    Phase 2 and Phase 3 grade 3 or higher per Common Terminology Criteria for Adverse Events (CTCAE V5.0)
19. Concentrations of fianlimab in serum [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
20. Concentrations of cemiplimab in serum [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
21. Anti-drug antibodies (ADA) in serum to fianlimab [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
22. ADA in serum to cemiplimab [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
23. Change from baseline in disease-related symptoms per Functional Assessment of Cancer Therapy-Melanoma (FACT-M) subscale [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3 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).
24. Change from baseline in functioning per European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (QoL) C30 (EORTC QLQ-C30) [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3 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.
25. Change from baseline in global health status/QoL per EORTC QLQ-C30 [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3
26. Change from baseline in overall health state per European Quality of Life Dimension 5 (EQ-5D-5L) [ Time Frame: Up to 4 years ]
    Phase 2 and Phase 3 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Clinical Trials Administrator; 844-734-6643; clinicaltrials@regeneron.com

Sponsors and Collaborators

Regeneron Pharmaceuticals

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

More Information

• Responsible Party: Regeneron Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT06190951
• Other Study ID Numbers: R3767-ONC-2208; 2022-502825-17-00 ( Registry Identifier: EU CT )
• First Posted: January 5, 2024
• Last Update Posted: May 15, 2024
• Last Verified: May 2024

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: All Individual Patient Data (IPD) that underlie publicly available results will be considered for sharing
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• 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.
• 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
• URL: https://vivli.org/

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Regeneron Pharmaceuticals:

Skin cancer; Fully resectable stage III melanoma; Fully resectable stage IV melanoma

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Pembrolizumab; Cemiplimab; Antineoplastic Agents, Immunological; Antineoplastic Agents; Immune Checkpoint Inhibitors; Molecular Mechanisms of Pharmacological Action