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

NCT03082534 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: 160621MISP 52211
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 4

Brief Summary

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.

Conditions

Nasopharynx Cancer; Sinonasal Carcinoma; Cutaneous Squamous Cell Carcinoma; Head and Neck Neoplasms; HNSCC; Lip SCC; Oral Cavity Cancer; Oropharynx Cancer; Larynx Cancer; Hypopharynx Cancer; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma

Keywords

Head and Neck Cancer; Pembrolizumab; Keytruda®; Cetuximab; Erbitux®; Recurrent; Metastatic; PD-1; PD-L1; non-EBV related Nasopharynx

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

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

  6 months from the time of study enrollment

Secondary Outcomes (8)

• Progression Free Survival Probability

  12 months from the time of study enrollment

• Overall Survival

  From the time of study enrollment until the date of death from any cause or completion of study, whichever came first, assessed up to 36 months

• Duration of Response

  Every 9 weeks from first on-treatment scan until disease progression or patient withdrawal from study or date of death from any cause, whichever came first, assessed up to 36 months

• Number of patients with grade 3 through grade 5 adverse events that are related to pembrolizumab and cetuximab, graded according to NCI CTCAE v4.03

  Upon study enrollment, then subsequently at the first visit of each cycle (cycle length is 21 days), at the time of any adverse event, through end of treatment study visit, assessed up to 36 months

• Correlative analyses

  Tumor specimens (archival or new specimen) should be obtained within 42 days of screening

Study Arms (4)

Cohort 1

EXPERIMENTAL

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).

Drug: Pembrolizumab, Cetuximab

Cohort 2

EXPERIMENTAL

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).

Drug: Pembrolizumab, Cetuximab

Cohort 3

EXPERIMENTAL

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).

Drug: Pembrolizumab, Cetuximab

Cohort 4

EXPERIMENTAL

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).

Drug: Pembrolizumab, Cetuximab

Interventions

Pembrolizumab, Cetuximab DRUG

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.

Also known as: Keytruda®, Erbitux®

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

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

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent.
• Histologically or cytologically proven squamous cell carcinoma of the head and neck (lip, oral cavity, oropharynx, larynx, hypopharynx, non-EBV related nasopharynx, sinonasal, cutaneous), not amenable to curative intent therapy.
• Platinum-refractory disease, or ineligible/unfit for platinum-based therapy
• Patients must have at least one measurable site of disease as defined by RECIST v.1.1, determined by investigator review
• Age ≥ 18 years.
• Eastern Cooperative Oncology Group (ECOG) Performance status 0 or 1.
• Patient has adequate hematologic, hepatic and renal function
• Female patient of childbearing potential has a negative serum or urine pregnancy within 72 hours prior to receiving the first dose of study medication.
• Female patient of childbearing potential agrees to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
• Male patient with a partner of childbearing potential agrees to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• \. Cetuximab-naïve patients may not have received cetuximab therapy in the recurrent/metastatic setting (treatment in curative setting permitted)
• \. PD-1/PD-L1 inhibitor-refractory patients must have documented disease progression after prior response to anti-PD-1/PD-L1 therapy (response defined as stable disease, partial or complete response)
• \. Cutaneous HNSCC must not be amenable to local treatment modalities, including surgery and/or radiation.

You may not qualify if:

• Patient has salivary gland primary.
• Patient is currently receiving or has received another investigational agent within 4 weeks prior to Day 1 of study.
• Patient has received chemotherapy or radiotherapy within 4 weeks prior to Day 1 of study. Prior palliative radiotherapy to metastatic lesion(s) is permitted, provided there is at least one measurable lesion that has not been radiated.
• Patient has received a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or baseline) from adverse events due to a previously administered agents.
• Patient has had major surgery or insufficient recovery from surgical-related trauma or wound healing within 14 days of Study Day 1.
• Patient has had a prior Grade ≥ 3 immune-related adverse event (irAE) while receiving any previous immunotherapy agent, or any unresolved irAE \> Grade 1.
• Patient has had prior Grade 4 infusion reaction to cetuximab.
• Patient has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Patient has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
• Note: Patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• Patient has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs).
• Notes:
• Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded.
• Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (\>10mg prednisone daily, or steroid equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.

Sponsors & Collaborators

• University of California, San Diego: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (4)

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

University of California Los Angeles Cancer Center

Los Angeles, California, 90095, United States

Location

University of Michigan Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Washington School of Medicine Cancer Center

St Louis, Missouri, 63110, United States

Location

Related Publications (1)

• Sacco AG, Chen R, Worden FP, Wong DJL, Adkins D, Swiecicki P, Chai-Ho W, Oppelt P, Ghosh D, Bykowski J, Molinolo A, Pittman E, Estrada MV, Gold K, Daniels G, Lippman SM, Natsuhara A, Messer K, Cohen EEW. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2021 Jun;22(6):883-892. doi: 10.1016/S1470-2045(21)00136-4. Epub 2021 May 11.

  PMID: 33989559 DERIVED

MeSH Terms

Conditions

Squamous Cell Carcinoma of Head and Neck; Mouth Neoplasms; Oropharyngeal Neoplasms; Laryngeal Neoplasms; Hypopharyngeal Neoplasms; Nasopharyngeal Neoplasms; Head and Neck Neoplasms; Recurrence; Neoplasm Metastasis

Interventions

pembrolizumab; Cetuximab

Condition Hierarchy (Ancestors)

Carcinoma, Squamous Cell; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Mouth Diseases; Stomatognathic Diseases; Pharyngeal Neoplasms; Otorhinolaryngologic Neoplasms; Pharyngeal Diseases; Otorhinolaryngologic Diseases; Laryngeal Diseases; Respiratory Tract Diseases; Respiratory Tract Neoplasms; Nasopharyngeal Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplastic Processes

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Assuntina Sacco, M.D.

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor, Medicine

Model Details: 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.

Study Record Dates

• First Submitted: February 28, 2017
• First Posted: March 17, 2017
• Study Start: March 28, 2017
• Primary Completion: July 21, 2025
• Study Completion: September 11, 2025
• Last Updated: January 28, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)