Pembrolizumab in Combination With CRT for LA-SCCHN

Each subject will participate in the trial from the time the subject signs the Informed
Consent Form (ICF) through the final protocol-specified contact. After a screening phase of
28 days, eligible subjects will receive treatment on Day -7 with a loading dose of the study
drug. This will continue during concurrent therapy with cisplatin and radiation, which will
begin on day 1. Treatment will continue until completion of therapy, documented confirmed
disease progression, unacceptable adverse event(s), intercurrent illness that prevents
further administration of treatment, investigator's decision to withdraw the subject, subject
withdraws consent, pregnancy of the patient, noncompliance with trial treatment or procedure
requirements; or administrative reasons. After the end of treatment, each patient will be
followed for 30 days for adverse event monitoring (serious adverse events will be collected
for 90 days after the end of treatment or 30 days after the end of treatment if the patient
initiates new anticancer therapy, whichever is earlier). Subjects who discontinue for reasons
other than disease progression will have post-treatment follow-up for disease status until
end of study disease progression, initiating a non-study cancer treatment, withdrawing
consent, or becoming lost to follow-up. All subjects will be followed by telephone for
overall survival until death, withdrawal of consent, or the Investigator is notified by
Sanford Research to discontinue follow-up

Inclusion Criteria:

1. Have histologically or cytologically-confirmed head and neck squamous cell carcinoma
of the oral cavity (excluding lip), oropharynx, hypopharynx, or larynx.

2. Have TNM clinical stage III, IVA, or IVB disease

3. Be eligible for curative-intent concurrent chemoradiation therapy

4. Be willing and able to provide written informed consent for the trial.

5. Be 18 years of age on day of signing informed consent.

6. Have measurable disease based on RECIST 1.1.

7. Be willing to provide tissue from a recently obtained core or excisional biopsy of a
tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days)
prior to initiation of treatment on Day -7. Subjects for whom newly-obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived specimen only upon agreement from Sanford Research.

8. Have a performance status of 0 or 1 on the ECOG Performance Scale.

9. Demonstrate adequate organ function as defined:

Absolute neutrophil count (ANC) ≥1,500 /mcL Platelets ≥100,000 / mcL Hemoglobin ≥9
g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of
assessment) Serum creatinine OR Measured or calculated creatinine clearance (GFR can
also be used in place of creatinine or CrCl) ≤1.5 X upper limit of normal (ULN) OR ≥60
mL/min for subject with creatinine levels > 1.5 X institutional ULN Serum total
bilirubin ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin
levels > 1.5 ULN AST (SGOT) and ALT (SGPT) ≤ 2.5 X ULN OR ≤ 5 X ULN for subjects with
liver metastases Albumin >2.5 mg/dL

10. Female subject of childbearing potential should have a negative urine or serum
pregnancy within 72 hours prior to receiving the first dose of study medication. If
the urine test is positive or cannot be confirmed as negative, a serum pregnancy test
will be required.

11. Female subjects 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. Subjects of
childbearing potential are those who have not been surgically sterilized or have not
been free from menses for > 1 year.

12. Male subjects 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.

Exclusion Criteria:

1. Patients may not be receiving any other investigational agents, chemotherapy,
immunotherapy, radiotherapy, or molecular targeted agents within 4 weeks of the start
of the study treatment.

2. Prior treatment with radiation to the head and neck

3. Patients with TNM Stage IVC disease

4. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.

5. 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.

6. Has a known history of active TB (Bacillus Tuberculosis)

7. Hypersensitivity to pembrolizumab or any of its excipients.

8. Has had 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 at baseline) from adverse events
due to agents administered more than 4 weeks earlier.

9. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy.

10. 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.

11. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis.

12. Has 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). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid
replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a
form of systemic treatment.

13. Has known history of, or any evidence of active, non-infectious pneumonitis.

14. Has an active infection requiring systemic therapy.

15. 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.

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

17. 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 120days after the last dose of trial treatment.

18. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

19. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

20. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).

21. Has received a live vaccine within 30 days of planned start of study therapy.