Pembrolizumab + Radiation for Locally Adv SCC of the Head and Neck (SCCHN) Not Eligible Cisplatin

This open label, phase II trial will enroll 29 subjects in order to evaluate the efficacy of
Pembrolizumab, concomitant with and following standard of care definitive radiation for
locally advanced squamous cell carcinoma head and neck patients who are not good candidates
for Cisplatin. Objectives include estimating progression free survival and overall survival,
response rates, safety and toxicity, and quality of life in these patients. Correlative
studies, based on serial blood collections and tumor samples, may be done under a separate
protocol based on availability of archival diagnostic tissue.

Inclusion Criteria:

- Be willing and able to provide written informed consent/assent for the trial

- Be greater than or equal to 18 years of age

- Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to 1

- Histologically or cytologically confirmed stage III-IV (non-metastatic) squamous cell
carcinoma of the head and neck as defined by American Joint Committee on Cancer.
Nasopharyngeal cancer patients will be excluded.

- Ineligible for high dose cisplatin therapy; the reason for ineligibility must be
defined.

- Demonstrate adequate organ function. All screening labs should be performed within 14
days of treatment initiation.

- No prior curative attempts for this cancer (i.e., surgery, radiation and/or other).

- Female patients of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. Serum
pregnancy test may be required.

- Female patients of childbearing potential should be willing 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 patients should agree 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.

- As determined by the enrolling physician or protocol designee, ability of the patient
to understand and comply with study procedures for the entire length of the study.

- Consent for the use of any residual material from biopsy (archival tissue) and serial
blood draws will be required for enrollment.

Exclusion Criteria:

- If currently participating in or has participated in a study of an investigational
agent or using an investigational device within 4 weeks of the first dose of
treatment.

- 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 trial
treatment.

- Has had a prior monoclonal antibody within 4 weeks prior to study Day 1 or who has not
recovered from adverse events due to agents administered more than 4 weeks earlier

- Had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks prior to study Day 1 or who has not recovered from adverse events due to a
previously administered agent.

- Has a known additional malignancy that is metastatic, progressing or requires active
treatment.

- Has an active autoimmune disease requiring systemic treatment within the past 3 months
or a documented history of clinically severe autoimmune disease even if resolved;
patients with vitiligo or resolved childhood asthma/atropy would be an exception to
this rule.

- Has clinical or radiologic evidence of interstitial lung disease or active,
non-infectious pneumonitis

- Has an active infection requiring systemic therapy.

- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the trial, interfere with the patient's
participation for the full duration of the trial, or is not in the best interest of
the patient to participate, in the opinion of the treating investigator.

- Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.

- Has inadequate home environment or social support to safely complete the trial
procedures.

- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the trial, starting with the pre-screening or screening visit
through 120 days after the last dose of trial treatment.

- Has received prior therapy with an anti-programmed cell death (PD-1), anti-PD-L1,
anti-PD-L1, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4)
antibody.

- Has a known history of Human Immunodeficiency Virus (HIV) HIV 1/2 antibodies) Has
known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C )e.g., HCV RNA
[qualitative] is detected).

- Has received a live vaccine within 30 days prior to the first dose of trial treatment.

- Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis