A Study of Cemiplimab With Chemotherapy and Immunotherapy in People With Head and Neck Cancer

NCT04722523 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 20-445
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Head and Neck Cancer; Head Cancer; HNSCC; Head and Neck Squamous Cell Carcinoma; Head Cancer Neck; Neck Cancer

Keywords

Cemiplimab; Platinum-Doublet Chemotherapy; Cetuximab; Head and Neck Cancer; Head Cancer; Neck Cancer; Head and Neck Squamous Cell Carcinoma; Memorial Sloan Kettering Cancer Center; 20-445; HNSCC)

Outcome Measures

Primary Outcomes (1)

• 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.

  1 year

Study Arms (2)

Head and Neck Squamous Cell Cancer/HNSCC

EXPERIMENTAL

Participants with locally advanced, resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.

Drug: Cisplatin; Drug: Carboplatin; Drug: Docetaxel; Drug: Cetuximab; Drug: Cemiplimab; Procedure: Surgical Resection of Primary +/- Neck Dissection; Radiation: Post-operative radiation therapy; Drug: Paclitaxel

Secondary Cohort

EXPERIMENTAL

Participants with locally advanced, resectable head and neck squamous cell carcinoma for which standard-of-care management would entail definitive surgery followed by adjuvant radiation +/- concurrent chemotherapy are eligible.

Drug: Cetuximab; Drug: Cemiplimab

Interventions

Post-operative radiation therapy RADIATION

Post-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.

Head and Neck Squamous Cell Cancer/HNSCC

Cisplatin DRUG

Cisplatin 75mg/m2 AUC 5 on weeks 2, 5, and 8

Head and Neck Squamous Cell Cancer/HNSCC

Carboplatin DRUG

Carboplatin AUC 5 on weeks 2, 5, and 8

Head and Neck Squamous Cell Cancer/HNSCC

Docetaxel DRUG

Docetaxel 75mg/m2 on weeks 2, 5, and 8

Head and Neck Squamous Cell Cancer/HNSCC

Cetuximab DRUG

Cetuximab 400mg/m2 on week 1, 250mg/m2 on weeks 2, 3, 4, 5, 6, 7, 8, 9, 10

Head and Neck Squamous Cell Cancer/HNSCC; Secondary Cohort

Cemiplimab DRUG

Cemiplimab 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

Head and Neck Squamous Cell Cancer/HNSCC; Secondary Cohort

Surgical Resection of Primary +/- Neck Dissection PROCEDURE

Twenty-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).

Head and Neck Squamous Cell Cancer/HNSCC

Paclitaxel DRUG

If 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.

Also known as: Taxol

Head and Neck Squamous Cell Cancer/HNSCC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ° Patients with recurrent and multiple primary head and neck cancers that are surgically resectable are eligible if the patient did not receive prior radiation or systemic therapy.
• Disease must be amenable to surgical resection.
• The patient must be a surgical candidate.
• Hemoglobin \> 9.0 g/dL
• Absolute neutrophil count (ANC) \>1.5 x 10\^9/L
• Platelet count \>100 x 10\^9/L
• Serum creatinine \<1.5 upper limit of normal (ULN) or estimated creatinine clearance (CrCl) \>30 mL/min
• Adequate hepatic function:
• Total bilirubin \<1.5 x upper limit of normal ULN)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both \< 3 x ULN
• Alkaline phosphatase (ALP) \<2.5 x ULN Note: For patients with Gilbert syndrome, total bilirubin \<3x ULN. Upper central must be documented appropriately as past medical history.
• Men and woman \>18 years old
• Eastern cooperative oncology group performance status \< 1

You may not qualify if:

• 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.
• Exceptions: Patients with vitiligo, type 1 diabetes mellitus, and endocrinopathies (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement, childhood asthma that is resolved, or psoriasis it does not require systemic treatment are permitted.
• Conditions requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalents) or other immunosuppressant medications within 14 days of treatment on study.
• Receipt of live attenuated vaccine within 30 days prior initiating treatment on study.
• Prior allogeneic stem cell transplantation, or autologous stem cell transplantation.
• Any infection requiring hospitalization and/or intravenous antibiotic therapy within 2 weeks of the start of treatment.
• Uncontrolled infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C virus (HBV or HCV) infection; or diagnosis of immunodeficiency.
• Patients with known HIV infection who have controlled infection (undetectable viral load (HIV RNA PCR) and CD4 count above 350, either spontaneously or on a stable antiviral regimen) are permitted. For patients with controlled HIV infection monitoring will be performed per local standards
• Patients with HBV (hepatitis B surface antigen positive; HBsAg+) who have controlled infection (serum HBV DNA PCR that is below the limit of detection and receiving anti-viral therapy for HBV) are permitted. Patients with controlled infections must undergo periodic monitoring of HBV DNA. Patients must remain on anti-viral therapy for at least 6 months be on the last dose of Cemiplimab.
• Patients were HCV antibody positive (HCV Ab+) who have controlled infection (undetectable HCV RNA by PCR, either spontaneously or in response to successful prior course of anti-HCV therapy) are permitted.
• History of immune-related pneumonitis with the last 5 years.
• History of interstitial lung disease (e.g., idiopathic pulmonary fibrosis, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of leuko-corticoids to assist with management.
• Known hypersensitivity or allergy to any of the excipients in the cemiplimab drug product.

Sponsors & Collaborators

• Regeneron Pharmaceuticals: collaborator
• Memorial Sloan Kettering Cancer Center: lead

Study Sites (7)

Memorial Sloan Kettering Basking Ridge (Limited Protocol Activities)

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (Limited Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (Limited Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Cancer Center @ Suffolk-Commack (Consent only)

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (Limited Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (Limited Protocol Activites)

Rockville Centre, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Head and Neck Neoplasms; Squamous Cell Carcinoma of Head and Neck

Interventions

Cisplatin; Carboplatin; Docetaxel; Cetuximab; cemiplimab; Paclitaxel

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Lara Dunn, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Lara Dunn, MD

CONTACT

646-608-3787; dunnl1@mskcc.org

David Pfister, MD

CONTACT

646-888-4237; pfisterd@MSKCC.ORG

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Six patients can be enrolled once the study has opened to the starting dose level. If 0-1 of the first 6 patients treated on study experience a DLT, then an additional 4 patients will be accrued to the study. If 0-2 of the 10 patients experience a DLT, then the combination will be deemed to be safe. If \>2 of the first 6 patients accrued or \>3 of 10 patients accrued experience a DLT, then patients will be treated at one dose level reduction.

Study Record Dates

• First Submitted: January 21, 2021
• First Posted: January 25, 2021
• Study Start: January 20, 2021
• Primary Completion (Estimated): June 20, 2026
• Study Completion (Estimated): June 20, 2026
• Last Updated: March 30, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)