Cemiplimab and Cetuximab Prior Salvage Surgery in Patients With Recurrent Oral Cavity and HPV-negative Oropharyngeal 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

• Subjects .18 years with histology-proven locoregionally recurrent oral cavity squamous cell carcinoma or HPV-negative OPSCC
• HPV testing is required only in oropharyngeal sites and must be negative
• Amenable to salvage surgery
• Disease recurrence at least 3 months after completion of curative-intent therapy, which must include at least surgery and post operatory radiation. Previous systemic therapy is the curative-setting is not required but allowed (e.g., neoadjuvant chemotherapy, concurrent chemotherapy).
• Measurable disease per RECIST 1.1
• Performance status ECOG of 0 or 1
• Willing to undergo baseline (if archival tumor specimen is not available) and on-treatment biopsy for correlative studies
• Laboratory measurements, blood counts:
• Hemoglobin ≥ 9 g/dL. Red blood cell transfusions are permitted to meet the hemoglobin inclusion criteria
• Absolute neutrophil count ≥ 1 x 109/mL
• Platelets ≥ 80 x 109/mL
• Laboratory measurements, renal function:
• a) Creatinine clearance ≥ 30 mL/min as assessed by the Cockcroft-Gault equation
• Laboratory measurements, hepatic function:
• AST and ALT ≤ 3 x ULN
• Total bilirubin ≤ 1.5 x ULN or ≤ 3.0 x ULN and primarily unconjugated if subject has a documented history of Gilbert's syndrome or genetic equivalent.
• Female subjects with reproductive potential must practice two effective contraceptive measures for the duration of study drug therapy and for at least 120 days after completion of study therapy. The two birth control methods can be either two barrier methods or a barrier method plus a hormonal method to prevent pregnancy. The following are considered adequate barrier methods of contraception: diaphragm, condom, copper intrauterine device, sponge, or spermicide. Appropriate hormonal contraceptives will include any registered and marketed contraceptive agent that contains an estrogen and/or a progestational agent (including oral, subcutaneous, intrauterine, or intramuscular agents).
• Male participants who are sexually active with women with reproductive potential must agree to use contraception for the duration of treatment and for at least 90 days after completion of study therapy.

You cannot join if

• Disease recurrence within 3 months after completion of definitive treatment (including surgery, post operatory, systemic therapy)
• Distant metastatic disease (M1), visceral and/or distant nodal
• Prior treatment with an t immune checkpoint inhibitor agent in the curative setting is allowed if over 1 year from the date of completion (last dose)
• Subjects with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of the first dose of study drug.
• Exceptions: Physiologic replacement doses are allowed even if they are >10 mg of prednisone/day or equivalent, as long as they are not being administered for immunosuppressive intent. Inhaled or topical steroids are permitted, provided that they are not for treatment of an autoimmune disorder.
• Subjects with active, known, or suspected autoimmune disease that has required systemic therapy within 5 years of the projected enrollment date. Exceptions: Subjects with vitiligo, type I diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that has resolved, or psoriasis that does not require systemic treatment are permitted.
• 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.
• Recipient of a solid organ transplant (other than corneal transplants)
• Prior allogeneic stem cell transplantation, or autologous stem cell transplantation
• History of previous malignancy other than malignancy treated with curative intent within less than 5 years. Participants with the following diagnoses represents an exception and may enroll if ≥ 1 year with no evidence of active disease before the first dose of the study drug:
• Locally advanced non-melanoma skin cancers with no current evidence of disease
• Melanoma in situ with no current evidence of disease
• Localized cancer of the prostate with prostate-specific antigen of <1 ng/mL
• Treated or localized well-differentiated thyroid cancer
• Treated cervical carcinoma in situ
• Treated ductal/lobular carcinoma in situ of the breast
• Evidence of uncontrolled, active infection, requiring systemic anti-bacterial, anti-viral or anti-fungal therapy ≤ 10 days prior to administration of cemiplimab and cetuximab. Subjects with known hepatitis B, hepatitis C (HCV), or HIV infection could go on study if the viral load is undetectable at screening.
• Disease or medical conditions that would substantially increase the risk-benefit ratio of participating in the study that include acute myocardial infarction within the last 6 months, unstable angina, uncontrolled diabetes mellitus, significant active infections, and congestive heart failure New York Heart Association Class III-IV
• Female participants who are pregnant or breast-feeding
• Known hypersensitivity to any of the study drugs, the metabolites, or formulation excipient

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

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

cetuximab. A recombinant, chimeric monoclonal antibody directed against the epidermal growth factor (EGFR) with antineoplastic activity. Cetuximab binds to the extracellular domain of the EGFR, thereby preventing the activation and subsequent dimerization of the receptor; the decrease in receptor activation and dimerization may result in an inhibition in signal transduction and anti-proliferative effects. This agent may inhibit EGFR-dependent primary tumor growth and metastasis. EGFR is overexpressed on the cell surfaces of various solid tumors. NCI Drug Dictionary

Treatments listed in the registry

• Cemiplimab (Drug): Given by IV
• Cetuximab (Drug): Given by IV

Na · Single Group · masking: None

As the registry describes them. Requirements to join, such as a tissue sample, are in the eligibility list above even when on-study procedures are optional. Ask the study team which steps apply to you.

• surgery: Part of the study plan

Main goals

• Safety and adverse events (AEs) (Through study completion; an average of 1 year)

Planned enrollment: 17 (estimated).

• MD Anderson Cancer Center, Houston, Texas

Site status as of Oct 30, 2026. Check the live record before contacting a site.

• ClinicalTrials.gov NCT06448026
• NCI Drug Dictionary: C121540
• NCI Drug Dictionary: C1723

Registry record reviewed as fetched Oct 30, 2026, last updated by the sponsor Jul 29, 2026. Public record; not medical advice.