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

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.

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.