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

The film gives the main points. The full list below is copied from the registry; the study team makes the final decision.

• Age18 Years to no maximum
• SexAll
• Healthy volunteersNo

You may be able to join if

• Key Inclusion Criteria:
• Have histologically confirmed (by local pathology) R/M HNSCC that is considered incurable by local therapies
• Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx (patients with cervical neck node SCC with occult primary as described in the protocol
• 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
• 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
• At least 1 lesion that is measurable by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as described in the protocol
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Adequate organ and bone marrow function as described in the protocol
• Key Exclusion Criteria:
• Medical Conditions
• 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
• Participants who have a primary tumor site of nasopharynx, paranasal sinus or salivary gland (any histology)
• Head and neck SCC with unknown primary site as described in the protocol
• 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
• 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
• 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
• Participants who have received prior systemic anticancer therapy in the R/M HNSCC setting as described in the protocol
• 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

This is how the treatment is meant to work. Whether it helps, and how safe it is, is what this trial is testing.

fianlimab. A monoclonal antibody directed against the inhibitory receptor lymphocyte activation gene-3 protein (LAG-3; LAG3; CD223), with potential immune checkpoint inhibitory and antineoplastic activities. Upon administration, fianlimab binds to LAG-3 expressed by tumor infiltrating lymphocytes (TILs) and blocks LAG-3 binding to tumor cells expressing major histocompatibility complex (MHC) class II molecules. This may activate antigen-specific T lymphocytes and enhance cytotoxic T-lymphocyte (CTL)-mediated tumor cell lysis, which leads to a reduction in tumor growth. LAG-3, a member of the immunoglobulin superfamily (IgSF), is expressed on various immune cells; its expression on TILs is associated with tumor-mediated immune suppression and the negative regulation of both cellular proliferation and T-cell activation. NCI Drug Dictionary

cemiplimab-rwlc. A human monoclonal antibody directed against the negative immunoregulatory human cell surface receptor programmed cell death 1 (PD-1, PCD-1) protein, with potential immune checkpoint inhibitory and antineoplastic activity. Upon administration, cemiplimab-rwlc binds to PD-1, inhibits its binding to the PD-1 ligand programmed cell death-1 ligand 1 (PD-L1), and prevents the activation of its downstream signaling pathways. This may restore immune function through the activation of cytotoxic T cells. PD-1, a transmembrane protein in the immunoglobulin superfamily expressed on activated T cells, negatively regulates T-cell activation and effector function when activated by its ligand; it plays an important role in tumor evasion from host immunity. NCI Drug Dictionary

Treatments listed in the registry

• FDC fianlimab+cemiplimab (Drug): Fixed-Dose Combination (FDC) Administered per the protocol
• Cemiplimab (Drug): Administered per the protocol
• Placebo (Drug): Administered per the protocol

Randomized · Parallel · masking: Quadruple

Main goals

• Overall Response Rate (ORR) (Up to 90 days after last study treatment, approximately 58 months)

Other goals

• Incidence of Adverse Events (AEs)
• Severity of AEs
• Incidence of Treatment Emergent Adverse Events (TEAEs)
• Incidence of immune-mediated Adverse Events (imAEs)
• Incidence of treatment-related AEs
• Incidence of Adverse Events of Special Interest (AESIs)
• Incidence of Serious Adverse Events (SAEs)
• Incidence of AEs leading to discontinuation
• Incidence of AEs leading to death
• Incidence of laboratory abnormalities
• Disease Control Rate (DCR) per investigator assessment
• Duration of Response (DOR) per investigator assessment or death, whichever occurs first
• Progression-Free Survival (PFS) per investigator assessment or death, whichever occurs first
• Concentrations of cemiplimab in serum
• Concentrations of fianlimab in serum
• Incidence of Anti-Drug Antibody (ADA) to fianlimab
• Titer of ADA to fianlimab

Planned enrollment: 120 (estimated).

• University of California Los Angeles, Los Angeles, California
• Samuel Oschin Cancer Center, Los Angeles, California
• Orlando Health, Orlando, Florida
• Emory University School of Medicine, Atlanta, Georgia
• Northwestern University, Evanston, Illinois
• St. Elizabeth Healthcare, Edgewood, Kentucky
• Norton Cancer Institute, Louisville, Kentucky
• Henry Ford Cancer Institute/Henry Ford Health System, Detroit, Michigan
• Oncology Hematology West P.C. dba Nebraska Cancer Specialists, Omaha, Nebraska
• University of Rochester, Rochester, New York
• Ohio State University, Columbus, Ohio
• Asplundh Cancer Pavilion, Willow Grove, Pennsylvania
• University of Tennessee Medical Center, Knoxville, Tennessee
• Vanderbilt-Ingram Cancer Center, Nashville, Tennessee
• Joe Arrington Cancer Research & Treatment Center, Lubbock, Texas
• Renovatio Clinical, The Woodlands, Texas
• Inova Schar Cancer Institute, Fairfax, Virginia
• Virginia Commonwealth University Massey Cancer Center, Richmond, Virginia

20 recruiting sites outside the US. Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06769698
• NCI Drug Dictionary: C132339
• NCI Drug Dictionary: C121540

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Oct 21, 2026. Public record; not medical advice.