Efficacy Study of Pembrolizumab in Relapsed, Locally Recurrent Squamous Cell Cancer of the Head and Neck

An Open-Label, Phase 2 Efficacy Study With Window of Opportunity Immune Assessment of Pembrolizumab in Relapsed, Locally Recurrent Squamous Cell Carcinoma of the Head and Neck (SCCHN)

The purpose of this study is to determine whether pembrolizumab, when given after salvage surgery, is effective in increasing the time a person with squamous cell cancer of the head and neck remains disease-free following locoregional disease recurrence.

Study Overview

• Status: Active, not recruiting
• Conditions: Squamous Cell Carcinoma of the Head and Neck
• Intervention / Treatment: Drug: Pembrolizumab

Detailed Description

The purpose of this study is to determine whether pembrolizumab, when given after salvage surgery, is effective in increasing the time a person with squamous cell cancer of the head and neck remains disease-free following locoregional disease recurrence.

This is a prospective, multi-center, open label, phase II study with a window of opportunity component in patients with recurrent squamous cell carcinoma of the head and neck (SCCHN) treated with adjuvant pembrolizumab following salvage surgery. Forty-five (45) patients will participate in this study to determine disease-free survival probability at 12 months. Secondary objectives include assessments of disease-free survival probability at 2 years, overall survival, adverse events and toxicity, and immune and molecular correlatives. For the window of opportunity component, patients will be randomized 3:1 in favor of receiving pembrolizumab 200 mg administered intravenously (IV) every three weeks for a maximum of two doses, versus placebo prior to salvage surgery. Approximately three to six weeks following the first dose of pembrolizumab, patients will undergo salvage surgery. Tumor tissue and blood will be collected at the time of surgery for immune correlative studies.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • San Francisco, California, United States, 94115
      • University of California San Francisco
    • Torrance, California, United States, 90505
      • University of California Los Angeles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Has pathologically confirmed SCCHN (oral cavity, oropharynx, larynx, hypopharynx) with evidence of local and/or locoregional recurrence. Laryngeal tumors will only be included if there is evidence of extralaryngeal spread, or there is associated nodal disease. For all other sites, superficial tumors can only be included if there is associated nodal disease.
• Has a documented disease-free interval (minimum 16 weeks) after initial curative intent therapy.
• Candidate for salvage resection.
• Able to provide tissue from diagnostic core biopsy of tumor lesion(s).
• Patient has adequate organ 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 adequate birth control.
• 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.

Exclusion Criteria:

• Patient has disease of nasopharyngeal carcinoma histology.
• Patient has evidence of metastatic disease.
• Patient is currently receiving or has received another investigational agent within 4 weeks prior to study Day 1.
• Patient has a diagnosis of immunodeficiency or is receiving systemic steroid therapy 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 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 received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1.
• Patients who have had major surgery or have insufficient recovery from surgical-related trauma or wound healing within 14 days from study Day 1.
• 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: (1) Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment within the past 2 years are not excluded. (2) 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 known history of, or any evidence of active, non-infectious pneumonitis.
• Patient receives chronic steroid use > 10 mg prednisone (or steroid equivalent) daily.
• Patient is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial.
• Patient has received immunotherapy with inhibitors of PD-1 or PD-L1, or CTLA-4 blocking antibodies within 4 months prior to study Day 1.
• Patient has known active Hepatitis B infection (defined as presence of HepB sAg and/ or Hep B DNA), active hepatitis C infection (defined as presence of Hep C RNA) and/or known Human Immunodeficiency Virus (HIV) carrier (HIV 1/2 antibodies).
• Patient has interstitial lung disease.
• Patient is an appropriate candidate for adjuvant radiation after salvage therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab; Pembrolizumab 200 mg will be administered by IV infusion every 3 weeks up to 12 months or until disease progression	Drug: Pembrolizumab; 200 mg will be administered by IV infusion every 3 weeks up to 12 months or until disease progression; Other Names: Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease-Free Survival	Disease-Free Survival	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Overall Survival	3 years
Disease-Free Survival at 2 years	Disease-Free Survival at 2 years	2 years
Safety: Incidence of Adverse Events, Serious Adverse Events, and Treatment Delays	Safety: Incidence of Adverse Events, Serious Adverse Events, and Treatment Delays	3 years

Collaborators and Investigators

• Sponsor: Assuntina G. Sacco, MD
• Collaborators: Merck Sharp & Dohme LLC
• Investigators: Study Director: Assuntina Sacco, MD, University of California, San Diego

Study record dates

Study Major Dates

• Study Start (Actual): July 6, 2016
• Primary Completion (Estimated): April 1, 2026
• Study Completion (Estimated): April 1, 2026

Study Registration Dates

• First Submitted: May 3, 2016
• First Submitted That Met QC Criteria: May 9, 2016
• First Posted (Estimated): May 11, 2016

Study Record Updates

• Last Update Posted (Actual): January 28, 2026
• Last Update Submitted That Met QC Criteria: January 26, 2026
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: cancer; pembrolizumab; SCCHN; squamous cell carcinoma head and neck
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms by Histologic Type; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Carcinoma; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: 151615

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No