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Pembrolizumab and Cetuximab in Treating Patients with Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Trial Status: Active

This phase II trial studies how well pembrolizumab and cetuximab work in treating patients with head and neck squamous cell carcinoma that has come back or spread to other places in the body. Immunotherapy with monoclonal antibodies, such as pembrolizumab and cetuximab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Inclusion Criteria

  • 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- Epstein–Barr virus [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 Response Evaluation Criteria in Solid Tumors (RECIST) version (v.)1.1, determined by investigator review
  • Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
  • Absolute neutrophil count >= 1.0 x 10^9/L
  • Platelet count >= 75 x 10^9/L
  • Hemoglobin >= 8.0 g/dL
  • Total bilirubin =< 1.5 x institution’s upper limit of normal
  • Aspartate aminotransferase (AST)/serum glutamic oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =< 2.5 x institutional upper limit of normal
  • Albumin >= 2.0 g/dL
  • Serum creatinine =< 1.5 x institution’s upper limit of normal (ULN), or creatinine clearance >= 60 ml/min
  • 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 * Note: Females of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • 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-naive 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

Exclusion Criteria

  • 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 (> 10 mg prednisone daily, or steroid equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab
  • Patient has a known history of active TB (Bacillus tuberculosis)
  • Patient has a known history of, or any evidence of active, non-infectious pneumonitis
  • Patient has a known history of chronic interstitial lung disease
  • Patient has an active infection requiring systemic therapy
  • Patient has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject’s participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Patient has a known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
  • Patient has known active hepatitis B infection (defined as presence of hepatitis B [HepB] surface antigen (sAg) and/ or Hep B deoxyribonucleic acid [DNA]), active hepatitis C infection (defined as presence of hepatitis C [Hep C] ribonucleic acid [RNA]) and/or known human immunodeficiency virus (HIV) carrier (HIV 1/2 antibodies)
  • Patient has received a live vaccine within 30 days of study day 1 * Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist) are live attenuated vaccines, and are not allowed
  • Patient has received any prior immunotherapy with inhibitors of PD-1 or PD-L1


Los Angeles
UCLA / Jonsson Comprehensive Cancer Center
Status: ACTIVE
Contact: Deborah Jean Lee Wong
Phone: 310-325-8252
San Diego
University of California San Diego
Status: ACTIVE
Contact: Assuntina Gesualda Sacco
Phone: 858-822-5210


Ann Arbor
University of Michigan Comprehensive Cancer Center
Contact: Francis Paul Worden
Phone: 734-936-0453


Saint Louis
Siteman Cancer Center at Washington University
Status: ACTIVE
Contact: Douglas Ray Adkins
Phone: 314-747-8475


I. To determine the clinical efficacy of pembrolizumab combined with cetuximab for patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC).


I. To determine 12 month progression-free survival probability.

II. To determine overall survival.

III. To determine duration of response.

IV. To assess safety and tolerability of pembrolizumab combined with cetuximab.

V. To evaluate the correlation between molecular markers and disease outcome.


Patients receive cetuximab intravenously (IV) over 60-120 minutes on days 1, 8, and 15 and pembrolizumab IV over 30 minutes on day 1. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 28 days and then every 3 months thereafter.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
University of California San Diego

Principal Investigator
Assuntina Gesualda Sacco

  • Primary ID MISP 52211
  • Secondary IDs NCI-2017-01183
  • ID NCT03082534