Testing the Addition of Anti-Cancer Drug, Cetuximab, to Standard of Care Treatment (Pembrolizumab) for Returning or Spreading Head and Neck Cancer After Previous Treatment

Recruiting now · Phase 3

Conditions studied: Metastatic Head and Neck Squamous Cell Carcinoma, Metastatic Hypopharyngeal Squamous Cell Carcinoma, Metastatic Laryngeal Squamous Cell Carcinoma, Metastatic Oral Cavity Squamous Cell Carcinoma, Metastatic Oropharyngeal Squamous Cell Carcinoma, Recurrent Head and Neck Squamous Cell Carcinoma, Recurrent Hypopharyngeal Squamous Cell Carcinoma, Recurrent Laryngeal Squamous Cell Carcinoma, Recurrent Neck Squamous Cell Carcinoma of Unknown Primary, Recurrent Oral Cavity Squamous Cell Carcinoma, Recurrent Oropharyngeal Squamous Cell Carcinoma, Refractory Head and Neck Squamous Cell Carcinoma, Refractory Hypopharyngeal Squamous Cell Carcinoma, Refractory Laryngeal Squamous Cell Carcinoma, Refractory Oral Cavity Squamous Cell Carcinoma, Refractory Oropharyngeal Squamous Cell Carcinoma, Stage IV Head and Neck Cutaneous Squamous Cell Carcinoma AJCC v8, Stage IV Hypopharyngeal Carcinoma AJCC v8, Stage IV Laryngeal Cancer AJCC v8, Stage IV Lip and Oral Cavity Cancer AJCC v8, Stage IV Oropharyngeal (p16-Negative) Carcinoma AJCC v8

In brief

This phase III trial compares the effect of adding cetuximab to pembrolizumab versus pembrolizumab alone in treating patients with head and neck squamous cell carcinoma (HNSCC) that has come back after a period of improvement (recurrent) and/or that has spread from where it first started (primary site) to other places in the body (metastatic). Cetuximab is in a class of medications called monoclonal antibodies. It binds to a protein called EGFR, which is found on some types of tumor cells. This may help keep tumor cells from growing. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread. Giving cetuximab and pembrolizumab together may be more effective at treating patients with recurrent and/or metastatic HNSCC than pembrolizumab alone.

Key facts

Study ID

NCT06589804

Run by

National Cancer Institute (NCI)

People needed

158

Starts

2025-03-27

Expected to finish

2029-11-30

Last updated by the study team

2026-08-05

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Histologically confirmed diagnosis head and neck squamous cell carcinomas (HNSCC).
• Previously untreated for recurrent and/or metastatic disease incurable by local therapies.
• Primary tumor location of oral cavity, oropharynx, larynx, or hypopharynx.
• Note: Other primary tumor sites of HNSCC, including nasopharynx primary tumor are not eligible. Unknown primary tumors may be eligible and can be enrolled at the discretion of the treatment team with approval by the study chair.
• Measurable disease.
• Must have platinum-refractory disease defined as disease progression during or ≤ 29 weeks after completion of definitive therapy (chemoradiation therapy) or adjuvant (post-operative) therapy.
• Patient must have a combined positive score PD-L1 positive (CPS >/= 1) tumor.
• Any radiation therapy must be completed >= 10 days prior to registration.
• Patients should not have received any prior treatment in the recurrent or metastatic setting.
• Prior therapy with neoadjuvant or induction anti PD-1/PD-L1 monoclonal antibody or cetuximab in the curative setting is allowed if last treatment dose was >= 26 weeks prior to registration without evidence of disease progression during that treatment period.
• Patient has not received a live vaccine within 30 days prior to registration.
• Patient does not have a history of any contraindication or has a severe hypersensitivity to any component of pembrolizumab or cetuximab (≥ grade 3).
• Patient has not received chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of immunosuppressive therapy within 7 days prior to registration.
• Patient with oropharyngeal cancer only must have negative results from testing of human papillomavirus (HPV) status defined as p16 immunohistochemistry (IHC) and/or HPV in situ hybridization (ISH).
• Note: A Clinical Laboratory Improvement Act (CLIA) certified circulating tumor HPV deoxyribonucleic acid (ctHPVDNA) assay can be used if tissue sample is not available.
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Absolute neutrophil count (ANC) ≥ 1,500/mm\^3.
• Platelet count ≥ 100,000/mm\^3.
• Hemoglobin (Hgb) ≥ 9 g/dL (if < 9 g/dL, then transfusions are acceptable to increase hemoglobin above 9 g/dL).
• Creatinine ≤ 1.5 x upper limit of normal (ULN) OR calculated (calc.) creatinine clearance ≥ 30 mL/min using the Cockcroft-Gault formula for participant with creatinine levels > 1.5 x institutional ULN.
• Total bilirubin ≤ 1.5 x ULN OR direct bilirubin < ULN for participant with total bilirubin > 1.5 x institutional ULN.
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase [SGPT]) ≤ 3.0 x ULN unless liver metastases are present in which case < 5.0 x ULN.
• Not pregnant and not nursing, because this study involves an agent that has known genotoxic, mutagenic, and teratogenic effects.
• Therefore, for women of childbearing potential only, a negative pregnancy test done ≤ 7 days prior to registration is required.

Where it is running

• Genesys Hurley Cancer Institute — Flint, Michigan, United States (enrolling)
• McFarland Clinic - Ames — Ames, Iowa, United States (enrolling)
• UChicago Medicine Northwest Indiana — Crown Point, Indiana, United States (enrolling)
• Mercy Hospital — Cedar Rapids, Iowa, United States (enrolling)
• Oncology Associates at Mercy Medical Center — Cedar Rapids, Iowa, United States (enrolling)
• McFarland Clinic - Trinity Cancer Center — Fort Dodge, Iowa, United States (enrolling)
• Mary Greeley Medical Center — Ames, Iowa, United States (enrolling)
• McFarland Clinic - Marshalltown — Marshalltown, Iowa, United States (enrolling)
• HaysMed — Hays, Kansas, United States (enrolling)
• University of Kansas Cancer Center — Kansas City, Kansas, United States (enrolling)
• Lawrence Memorial Hospital — Lawrence, Kansas, United States (enrolling)
• The University of Kansas Cancer Center - Olathe — Olathe, Kansas, United States (enrolling)
• University of Kansas Cancer Center-Overland Park — Overland Park, Kansas, United States (enrolling)
• University of Kansas Hospital-Indian Creek Campus — Overland Park, Kansas, United States (enrolling)
• Salina Regional Health Center — Salina, Kansas, United States (enrolling)
• University of Kansas Health System Saint Francis Campus — Topeka, Kansas, United States (enrolling)
• University of Kansas Hospital-Westwood Cancer Center — Westwood, Kansas, United States (enrolling)
• University of Maryland/Greenebaum Cancer Center — Baltimore, Maryland, United States (enrolling)
• Boston Medical Center — Boston, Massachusetts, United States (enrolling)
• Trinity Health Saint Joseph Mercy Hospital Ann Arbor — Ann Arbor, Michigan, United States (enrolling)
• Trinity Health IHA Medical Group Hematology Oncology - Brighton — Brighton, Michigan, United States (enrolling)
• Trinity Health IHA Medical Group Hematology Oncology - Canton — Canton, Michigan, United States (enrolling)
• Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital — Chelsea, Michigan, United States (enrolling)
• Cancer Hematology Centers - Flint — Flint, Michigan, United States (enrolling)
• Hurley Medical Center — Flint, Michigan, United States (enrolling)

Full record on ClinicalTrials.gov

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