Home › Trials › NCT06769698

Adding fianlimab to cemiplimab versus cemiplimab alone for 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

PHASE2 · Regeneron Pharmaceuticals · NCT06769698

This test sees if adding the experimental drug fianlimab to cemiplimab works better than cemiplimab alone for people with recurrent or metastatic PD-L1–positive head and neck squamous cell carcinoma.

Quick facts

PhasePHASE2
Study typeInterventional
Enrollment120 (estimated)
Ages18 Years and up
SexAll
SponsorRegeneron Pharmaceuticals (industry)
Drugs / interventionsprednisone, fianlimab, cemiplimab
Locations10 sites (Orlando, Florida and 9 other locations)
Trial IDNCT06769698 on ClinicalTrials.gov

What this trial studies

This randomized Phase 2 trial compares the combination of fianlimab (REGN3767) plus cemiplimab to cemiplimab plus placebo in people with recurrent or metastatic head and neck squamous cell carcinoma who have not received prior systemic therapy for their recurrent/metastatic disease. Participants must have PD-L1 expression (CPS ≥1), measurable disease, and good performance status, and are treated at participating US sites. The study will measure anti-tumor activity as well as monitor safety, blood levels of the drugs, and whether patients develop antibodies to the study drugs. Additional translational research samples may be collected to better understand how the drugs work and tumor biology.

Who should consider this trial

Good fit: Ideal candidates are adults with histologically confirmed recurrent or metastatic HNSCC (primary in the oral cavity, oropharynx, larynx, or hypopharynx), PD-L1 CPS ≥1, measurable disease, ECOG 0–1, and no prior systemic therapy for their recurrent/metastatic disease.

Not a fit: Patients are unlikely to benefit if they have PD-L1 CPS <1, non-squamous histology, poor performance status, or prior systemic treatment for recurrent/metastatic disease.

Why it matters

Potential benefit: If successful, the combination could improve response rates and potentially prolong disease control compared with cemiplimab alone.

How similar studies have performed: PD-1 inhibitors like cemiplimab have proven benefit in HNSCC, and combining PD-1 blockade with LAG-3 targeting agents has shown added benefit in other cancers, but this specific combination is still being tested in head and neck cancer.

Eligibility criteria

Show full inclusion / exclusion criteria 
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

Where this trial is running

Orlando, Florida and 9 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.

View on ClinicalTrials.gov →

Conditions: Head and Neck Squamous Cell Carcinoma, Recurrent or Metastatic, Positive for Programmed Death Ligand 1 Expression, Human Papillomavirus

Last reviewed 2026-05-15 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.