Cemiplimab with Chemotherapy and Immunotherapy (Cetuximab) for the Treatment of Resectable, Locally Advanced Head and Neck Squamous Cell Cancer
This phase I trial studies the side effects and tolerability of cemiplimab, platinum-doublet chemotherapy, and cetuximab in treating patients with head and neck squamous cell cancer that can be removed by surgery (resectable) and has spread to nearby tissue or lymph nodes (locally advanced). Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as cisplatin, carboplatin, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Immunotherapy with cetuximab, may induce changes in body's immune system and may interfere with the ability of tumor cells to grow and spread. Giving cemiplimab, platinum-doublet chemotherapy, and cetuximab may kill more tumor cells.
Inclusion Criteria
- 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 (American Joint Committee on Cancer [AJCC], 8th edition [ed.]) without evidence of distant metastasis (M0) based on positron emission tomography (PET)/computed tomography (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 * For patients 11-30, enrollment is restricted to a maximum of 6 patients with stage cT4aN0-3, M0 disease
- 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
- Total bilirubin < 1.5 x upper limit of normal ULN * Note: For patients with Gilbert syndrome, total bilirubin < 3 x ULN. Upper central must be documented appropriately as past medical history
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) both < 3 x ULN
- Alkaline phosphatase (ALP) < 2.5 x ULN
- Men and woman >= 18 years old
- Eastern cooperative oncology group performance status =< 1
Exclusion Criteria
- 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 ribonucleic acid (RNA) polymerase chain reaction (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
- Patients with a history of solid organ transplant (exception: corneal transplant)
- Any medical comorbidity, physical examination finding, or metabolic dysfunction, or clinical laboratory abnormality that in the opinion of the investigator renders the patient unsuitable for participation in a clinical trial due to high safety risks
- Women with a positive serum or urine beta-human chorionic gonadotropin (hCG) pregnancy test at screening/baseline visit. If positive, pregnancy must be ruled out by ultrasound for patient to be eligible
- Breast-feeding women
- Women of childbearing potential who are sexually active and aren’t willing to practice highly effective contraception prior to the first dose of cemiplimab, during the study, and for at least 180 days after the last dose. Highly effective contraceptive measures include: * Stable use of combined estrogen and progesterone containing hormonal contraception or progesterone and-only hormonal contraception associated with inhibition of ovulation initiated 2 or more menstrual cycles prior to screening * Intrauterine device; intrauterine hormone-releasing system * Bilateral tubal ligation * Vasectomized partner and/or * Sexual abstinence
Additional locations may be listed on ClinicalTrials.gov for NCT04722523.
Locations matching your search criteria
United States
New Jersey
Basking Ridge
Middletown
Montvale
New York
Commack
New York
West Harrison
PRIMARY OBJECTIVE:
I. To assess the safety and tolerability of the neoadjuvant combination regimen of cemiplimab with cisplatin or carboplatin, docetaxel, and cetuximab.
SECONDARY OBJECTIVES:
I. To assess the number of patients whose definitive surgery was delayed due to toxicity of neoadjuvant therapy.
II. To assess clinical to pathologic downstaging in response to neoadjuvant combination therapy.
EXPLORATORY OBJECTIVES:
I. To assess the correlation between clinical (based on imaging following neoadjuvant treatment) and pathologic staging.
II. To assess preliminary objective response rate per Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 of the neoadjuvant treatment in patients with measurable disease at baseline.
III. To describe modifications or reduction in the extensiveness of surgical resection when comparing the planned pre-treatment surgical resection with the actual surgical resection that followed neoadjuvant treatment.
IV. To assess disease-free survival at 6 months and 5 years, as well as overall survival and treatment-associated toxicity at 5 years post-surgery in the patients who did not receive standard adjuvant treatment (radiation +/- chemotherapy) but received adjuvant cemiplimab.
V. To assess how pre-treatment tumor PD-L1 expression, mutation burden, neoantigen load, and tumor infiltrating lymphocytes, along with transcriptomic changes in tumor micro-environment correlates with pathologic response to the neoadjuvant study treatment.
VI. To assess how pretreatment peripheral blood soluble PD-1 and PD-L1 and T cell receptor (TCR) repertoire evaluating clonality and diversity, along with changes in peripheral blood T-cell phenotype, myeloid-derived suppressor cell (MDSC) cell population, and circulating tumor deoxyribonucleic acid (DNA) correlate with pathologic response to the neoadjuvant study treatment.
OUTLINE: Patients are assigned to 1 of 2 cohorts.
PRIMARY COHORT: Patients receive loading dose of cetuximab intravenously (IV) and cemiplimab IV over 30 minutes at week 1. Patients then receive cisplatin IV or carboplatin IV and docetaxel IV at weeks 2, 5, and 8, cemiplimab IV over 30 minutes at weeks 4, 7, and 10, and cetuximab IV at weeks 2-10. Treatment repeat every 21 days for 3 cycles in the absence of disease progression or unacceptable toxicity. Beginning 28 days after neoadjuvant therapy, patients undergo surgical resection. Based on pathologic staging, patients may undergo radiation therapy per standard of care or continue to receive cemiplimab IV over 30 minutes at weeks 16, 19, 22, 25, 28, 31, 34, and 37 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy during screening and computed tomography (CT) scan or magnetic resonance imaging (MRI) and positron emission tomography (PET) scan and blood sample collection throughout the study.
SECONDARY COHORT: Patients receive loading dose of cetuximab IV and cemiplimab IV over 30 minutes at week 1. Patients then receive cetuximab IV once a week (QW) for a total of 9 treatments and cemiplimab IV over 30 minutes every 21 days for a total of 4 treatments in the absence of disease progression or unacceptable toxicity. Beginning 28 days after neoadjuvant therapy, patients undergo surgical resection. Based on pathologic staging, patients may undergo radiation therapy per standard of care or receive pembrolizumab IV at weeks 16, 19, 22, 25, 28, 31, 34, and 37 in the absence of disease progression or unacceptable toxicity. Patients may undergo tumor biopsy during screening and CT scan or MRI and PET scan and blood sample collection throughout the study.
After completion of study treatment, patients are followed up at 1 year.
Trial PhasePhase I
Trial Typetreatment
Lead OrganizationMemorial Sloan Kettering Cancer Center
Principal InvestigatorLara Ann Dunn
- Primary ID20-445
- Secondary IDsNCI-2021-00697
- ClinicalTrials.gov IDNCT04722523