Neoplasms

All Conditions

Symptoms and General Pathology

Mouth and Tooth Diseases

Respiratory Tract (Lung and Bronchial) Diseases

Ear, Nose, and Throat Diseases

Rare Diseases

Carcinoma

Carcinoma, Squamous Cell

Recurrence

Head and Neck Neoplasms

Mouth Neoplasms

Laryngeal Diseases

Squamous Cell Carcinoma of Head and Neck

Oropharyngeal Neoplasms

Laryngeal Neoplasms

Nasopharyngeal Neoplasms

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Neoplasms, Squamous Cell

Mouth Diseases

Stomatognathic Diseases

Pharyngeal Neoplasms

Otorhinolaryngologic Neoplasms

Pharyngeal Diseases

Otorhinolaryngologic Diseases

Respiratory Tract Diseases

Respiratory Tract Neoplasms

Nasopharyngeal Diseases

Oral Cancer

Hypopharyngeal Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Pembrolizumab

Cetuximab

Immunoglobulins

Immunoglobulin G

Mitogens

Immunoglobulins, Intravenous

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

PD-1/PD-L1 inhibitor-naïve, cetuximab-naïve

Pembrolizumab (Keytruda®):

Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks.

Cetuximab (Erbitux®):

The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

PD-1/PD-L1 inhibitor-refractory, cetuximab-naïve

Pembrolizumab (Keytruda®):

Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks.

Cetuximab (Erbitux®):

The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

PD-1/PD-L1 inhibitor-refractory, cetuximab-refractory

Pembrolizumab (Keytruda®):

Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks.

Cetuximab (Erbitux®):

The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

cutaneous HNSCC

Pembrolizumab (Keytruda®):

Pembrolizumab is administered on an outpatient basis. 200 mg pembrolizumab will be administered as a 30 minute (-5 min/+10 min) intravenous (IV) infusion every 3 weeks.

Cetuximab (Erbitux®):

The initial cetuximab dose of 400mg/m2 is administered on Cycle 1, Day 1 as a 120-minute IV infusion (maximum infusion rate 10mg/min).1 Subsequent weekly cetuximab doses of 250mg/m2 are administered as 60-minute IV infusions (maximum infusion rate 10mg/min).

Pembrolizumab (KEYTRUDA®; MK-3475) is a potent and highly selective humanized monoclonal antibody (mAb) of the immunoglobulin G4 (IgG4)/kappa isotype designed to directly block the interaction between PD-1 and its ligands, programmed cell death ligand 1 (PD-L1) and programmed cell death ligand 2 (PD-L2). This blockade enhances functional activity of the target lymphocytes to facilitate tumor regression and ultimately immune rejection.

Cetuximab (Erbitux®) binds specifically to the epidermal growth factor receptor (EGFR) on both normal and tumor cells, and competitively inhibits the binding of EGF and other ligands, such as transforming growth factor-alpha. Cetuximab can mediate antibody-dependent cellular cytotoxicity (ADCC), with in vitro assays and in vivo animal studies demonstrating that cetuximab inhibits the growth and survival of tumor cells expressing EGFR.

Pembrolizumab, Cetuximab

Assuntina Sacco, M.D.

This is a prospective, multi-center, open-label, non-randomized, multi-arm phase II trial to evaluate the efficacy of combination therapy with pembrolizumab and cetuximab for patients with recurrent/metastatic HNSCC. There will be four patient cohorts, including a PD-1/PD-L1 inhibitor-naïve, cetuximab-naïve arm (Cohort 1), a PD-1/PD-L1 inhibitor-refractory, cetuximab-naïve arm (Cohort 2), a PD-1/PD-L1 inhibitor-refractory, cetuximab-refractory arm (Cohort 3), and a cutaneous HNSCC arm (Cohort 4). A total of 83 patients (33 in Cohort 1, 25 in Cohort 2, 15 in Cohort 3, and 10 in Cohort 4) will be eligible to enroll. Patients will be enrolled at 4 sites: UC San Diego Moores Cancer Center, UC Los Angeles Jonsson Comprehensive Cancer Center, University of Michigan Comprehensive Cancer Center, and University of Washington Siteman Cancer Center.

Primary Objectives:

To determine the clinical efficacy of pembrolizumab combined with cetuximab for patients with R/M HNSCC.

1. Cohort 1 (PD-1/PD-L1 inhibitor-naïve, cetuximab-naïve): clinical efficacy defined as overall response rate.
2. Cohort 2 (PD-1/PD-L1 inhibitor-refractory, cetuximab-naïve): clinical efficacy defined as overall response rate.
3. Cohort 3 (PD-1/PD-L1 inhibitor-refractory, cetuximab-refractory): clinical efficacy defined as overall response rate.
4. Cohort 4 (cutaneous HNSCC): clinical efficacy defined as overall response rate.

Secondary Objectives:

1. To determine 12 month progression-free survival probability.
2. To determine overall survival.
3. To determine duration of response.
4. To assess safety and tolerability of pembrolizumab combined with cetuximab.
5. To evaluate the correlation between molecular markers and disease outcome.

Open-label, non-randomized, multi-arm phase II trial of pembrolizumab combined with cetuximab for patients with recurrent/metastatic head and neck squamous cell carcinoma

1. Cohort 1 (PD-1/PD-L1 inhibitor-naïve, cetuximab-naïve): clinical efficacy defined as overall response rate.
2. Cohort 2 (PD-1/PD-L1 inhibitor-refractory, cetuximab-naïve): clinical efficacy defined as overall response rate.
3. Cohort 3 (PD-1/PD-L1 inhibitor-refractory, cetuximab-refractory): clinical efficacy defined as overall response rate.
4. Cohort 4 (cutaneous HNSCC): clinical efficacy defined as overall response rate.

Pembrolizumab Combined With Cetuximab for Treatment of Recurrent/Metastatic Head & Neck Squamous Cell Carcinoma

An Open-label, Non-randomized, Multi-arm, Phase II Trial to Evaluate the Efficacy of Pembrolizumab Combined With Cetuximab in Patients With Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma (HNSCC)

Proportion of patients with partial or complete response in tumor burden as defined by RECIST

Probability of no disease progression or death from any cause at 12 months from the time of study enrollment

Time from study enrollment to death from any cause

Time from documentation of tumor response to disease progression

Description, grade (per CTCAE v4.03), seriousness and relatedness

Tumor tissue biomarkers correlated with outcome to pembrolizumab or cetuximab, such as PD-L1 expression, EGFR expression, p16 status, and immunophenotyping

Blood biomarkers correlated with outcome to pembrolizumab or cetuximab, including T cell receptor (TCR) sequencing

Blood biomarkers correlated with outcome to pembrolizumab or cetuximab, including Epstein-Barr virus plasma DNA titers

Whole exome sequencing for neoantigen discovery

Spots Global Cancer Trial Database for pembrolizumab, cetuximab