The purpose of this study is to find out whether combining the standard chemotherapy for head and neck cancer with the immunotherapy drugs cetuximab and cemiplimab (the study drug) is a safe treatment for head and neck cancer, and whether receiving this combination treatment before surgery may allow participants to forgo the standard radiation treatment after surgery.
Pathologically (histologically or cytologically) proven diagnosis of squamous cell carcinoma of the head and neck that has arisen from the oral cavity, oropharynx, nasal cavity, paranasal sinuses, larynx, or hypopharynx
Clinical stage T1, N2-3; T2, N1-3, T3/T4a, Any N (AJCC, 8th ed.) without evidence of distant metastasis (M0) based on PET/CT or CT chest, abdomen, and pelvis, for which standard-of-care treatment would entail surgical resection with adjuvant radiation +/- chemotherapy.
Disease must be amenable to surgical resection.
The patient must be a surgical candidate.
Prior radiation and systemic therapy for a head and neck cancer.
Oral cavity cancer that is not amenable to surgical resection or the patient is not a surgical candidate.
Active or prior documented autoimmune or inflammatory disorders that have been treated with steroids or immunomodulator therapy in the past 5 years.
Conditions requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressant medications within 14 days of treatment on study.
Sequential
Cisplatin
DrugCisplatin 75mg/m2 AUC 5 on weeks 2, 5, and 8
Carboplatin
DrugCarboplatin AUC 5 on weeks 2, 5, and 8
Docetaxel
DrugDocetaxel 75mg/m2 on weeks 2, 5, and 8
Cetuximab
DrugCetuximab 400mg/m2 on week 1, 250mg/m2 on weeks 2, 3, 4, 5, 6, 7, 8, 9, 10
Cemiplimab
DrugCemiplimab 350mg on weeks 2, 5, 8, 11; if adjuvant radiation +/- chemotherapy is omitted, Cemiplimab will be administered on weeks 16, 19, 22, 25, 28, 31, 34, 37
Surgical Resection of Primary +/- Neck Dissection
Procedure/SurgeryTwenty-eight days (+ 7 days) following the 3rd cycle of neoadjuvant therapy, patients will then undergo definitive surgical resection of the primary site +/- neck dissection(s).
Post-operative radiation therapy
RadiationPost-operative radiation therapy +/- radiosensitizing agent(s) will be administered per standard-of-care based on pathologic staging of the surgical specimen. If there is an excellent response to treatment with a high degree of downstaging the addition of adjuvant radiation may be omitted if NCCN guidelines are met. If the pathologic stage following induction systemic therapy and surgery is ypT1-2N0 without the presence of adverse features that include positive margins or a combination of perineural invasion, vascular invasion, and a depth of invasion of \>0.5mm, adjuvant radiation will not be administered, consistent with the NCCN guidelines \[2\]. Otherwise, patients will receive adjuvant RT-based treatment with standard radiation techniques.
Paclitaxel
DrugIf participants are unable to receive Docetaxel due to lack of insurance approval or due to an allergic reaction, Docetaxel can be substituted with Paclitaxel. Paclitaxel would be dosed at 90 mg/m2 on weeks 2, 3, 5, 6, 8 and 9.
Incidence of toxicities graded according to NCI CTCAE
The primary endpoint is safety and tolerability, which will be evaluated by a description of observed adverse events by grades. All toxicities will be graded according to NCI CTCAE, Version5.0. The regimen will be deemed safe and well tolerated if there are 2 or fewer DLTs out of 10 patients enrolled. A DLT is defined as any non-hematologic grade 3 or greater adverse event as defined by CTCAE v5.0 that is thought to be related to the addition of Cemiplimab to the combination of a platinum-doublet with cetuximab.
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Memorial Sloan Kettering Cancer Center
Lead sponsor
Regeneron Pharmaceuticals
Collaborator
