A Study to See if Giving Fianlimab and Cemiplimab Together is Better Than Cemiplimab Alone at Treating Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Phase II Randomized Study of Fianlimab Plus Cemiplimab Versus Cemiplimab Plus Placebo in First-Line Treatment of Participants With Recurrent or Metastatic (R/M) Head and Neck Squamous Cell Carcinoma (HNSCC) That Is Positive for PD-L1 Expression

This study is researching an experimental drug called fianlimab (also called REGN3767), combined with a medication called cemiplimab compared against cemiplimab combined with placebo (a placebo looks like a treatment but does not contain any real medicine), collectively called "study drugs" in this form.

The study is focused on participants with head and neck cancers who have not been previously treated for head and neck cancer that has come back or spread to other parts of the body, referred to as recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).

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

• What side effects may happen from taking the study drugs
• How much of each study drug is in the blood at different times
• Whether the body makes antibodies against the study drug(s) individually (which could make the study drugs less effective or could lead to side effects)
• Compatible research to better understand the study drugs and HNSCC

Study Overview

• Status: Recruiting
• Conditions: Head and Neck Squamous Cell Carcinoma (HNSCC)
• Intervention / Treatment: Drug: Placebo; Drug: FDC fianlimab+cemiplimab; Drug: Cemiplimab

• Study Type: Interventional
• Enrollment (Estimated): 120
• Phase: Phase 2

Contacts and Locations

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

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3050
      • Recruiting
      • Peter MacCallum Cancer Centre (PMCC)
• United States
  • Florida
    • Orlando, Florida, United States, 32806
      • Recruiting
      • Orlando Health
  • Georgia
    • Atlanta, Georgia, United States, 30308
      • Recruiting
      • Emory University School of Medicine
  • Kentucky
    • Edgewood, Kentucky, United States, 41017
      • Recruiting
      • St. Elizabeth Healthcare
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • Norton Cancer Institute
  • Nebraska
    • Omaha, Nebraska, United States, 68130
      • Recruiting
      • Oncology Hematology West P.C. dba Nebraska Cancer Specialists
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Recruiting
      • Vanderbilt-Ingram Cancer Center
  • Texas
    • Lubbock, Texas, United States, 79410
      • Recruiting
      • Joe Arrington Cancer Research & Treatment Center
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Inova Schar Cancer Institute

Participation Criteria

Eligibility Criteria

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

Description

Key Inclusion Criteria:

1. Have histologically confirmed (by local pathology) R/M HNSCC that is considered incurable by local therapies
2. Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx (patients with cervical neck node SCC with occult primary as described in the protocol
3. PD-L1 expression Combined Positive Score (CPS) ≥1 documented with a previously PD-L1 obtained Immunohistochemistry (IHC) result prior to screening, as described in protocol
4. Oropharynx cancer participants only: HPV status, based on a previously documented result prior to screening, must have been established in a surgical biopsy specimen or a core biopsy specimen as described in the protocol
5. At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as described in the protocol
6. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
7. Adequate organ and bone marrow function as described in the protocol

Key Exclusion Criteria:

Medical Conditions

1. Participants who have Progressive Disease (PD) within 6 months of completion of curatively intended systemic treatment for locoregionally advanced HNSCC as described in the protocol
2. Participants who have a primary tumor site of nasopharynx, paranasal sinus or salivary gland (any histology)
3. Head and neck SCC with unknown primary site as described in the protocol
4. Participants with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date as described in the protocol
5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management

6. History or current evidence of significant cardiovascular disease including, myocarditis, congestive heart failure (as defined by New York Heart Association Functional Classification III and IV), unstable angina, serious uncontrolled arrhythmia, and myocardial infarction 6 months prior to study enrollment.

   Prior/Concomitant Therapy

7. Participants who have received prior systemic anticancer therapy in the R/M HNSCC setting as described in the protocol
8. Participants with a condition requiring corticosteroid therapy (>10 mg prednisone/prednisolone/day or equivalent) within 14 days of the first dose of study drug as described in the protocol

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1; Approximately 60 participants with HPV (human papillomavirus) positive HNSCC. Randomized 1:1 to Fianlimab + Cemiplmab Fixed Dose Combination (FDC) versus Cemiplimab + Placebo.	Drug: Placebo; Administered per the protocol; Drug: FDC fianlimab+cemiplimab; Fixed-Dose Combination (FDC) Administered per the protocol; Other Names: REGN2810; Libtayo; REGN3767; Drug: Cemiplimab; Administered per the protocol; Other Names: Libtayo; R2810
Experimental: Cohort 2; Approximately 60 participants with HPV negative HNSCC. Randomization is the same as in Cohort 1.	Drug: Placebo; Administered per the protocol; Drug: FDC fianlimab+cemiplimab; Fixed-Dose Combination (FDC) Administered per the protocol; Other Names: REGN2810; Libtayo; REGN3767; Drug: Cemiplimab; Administered per the protocol; Other Names: Libtayo; R2810

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Overall Response Rate (ORR)	Up to 90 days after last study treatment, approximately 58 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Adverse Events (AEs)		Up to 90 days after last study treatment, approximately 58 months
Severity of AEs		Up to 90 days after last study treatment, approximately 58 months
Incidence of Treatment Emergent Adverse Events (TEAEs)		Up to 90 days after last study treatment, approximately 58 months
Incidence of immune-mediated Adverse Events (imAEs)		Up to 90 days after last study treatment, approximately 58 months
Incidence of treatment-related AEs		Up to 90 days after last study treatment, approximately 58 months
Incidence of Adverse Events of Special Interest (AESIs)		Up to 90 days after last study treatment, approximately 58 months
Incidence of Serious Adverse Events (SAEs)		Up to 90 days after last study treatment, approximately 58 months
Incidence of AEs leading to discontinuation		Up to 90 days after last study treatment, approximately 58 months
Incidence of AEs leading to death		Up to 90 days after last study treatment, approximately 58 months
Incidence of laboratory abnormalities	Per National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0	Up to 90 days after last study treatment, approximately 58 months
Disease Control Rate (DCR) per investigator assessment		Up to 90 days after last study treatment, approximately 58 months
Duration of Response (DOR) per investigator assessment or death, whichever occurs first		Up to 90 days after last study treatment, approximately 58 months
Progression-Free Survival (PFS) per investigator assessment or death, whichever occurs first		Up to 90 days after last study treatment, approximately 58 months
Concentrations of cemiplimab in serum		Up to 90 days after last study treatment, approximately 58 months
Concentrations of fianlimab in serum		Up to 90 days after last study treatment, approximately 58 months
Incidence of Anti-Drug Antibody (ADA) to fianlimab		Up to 90 days after last study treatment, approximately 58 months
Titer of ADA to fianlimab		Up to 90 days after last study treatment, approximately 58 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2026
• Primary Completion (Estimated): June 4, 2028
• Study Completion (Estimated): December 28, 2030

Study Registration Dates

• First Submitted: January 6, 2025
• First Submitted That Met QC Criteria: January 6, 2025
• First Posted (Actual): January 10, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Human Papillomavirus (HPV); Recurrent or Metastatic (R/M); Positive for Programmed Death Ligand 1 (PD-L1) Expression
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Neoplastic Processes; Carcinoma; Carcinoma, Squamous Cell; Pathological Conditions, Signs and Symptoms; Squamous Cell Carcinoma of Head and Neck; Recurrence; Neoplasm Metastasis; Antineoplastic Agents, Immunological; Antineoplastic Agents; cemiplimab
• Other Study ID Numbers: R3767-ONC-2431; 2024-517620-19-00 (Ctis: 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 or has globally discontinued development of the product for all indications on or after April 2020 and has no plans for future development
• made the study results publicly available (e.g., scientific publication, scientific conference, clinical trial registry)
• the legal authority to share the data, and
• 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