Pembrolizumab in HNSCC With Residual Disease After Radiation

The primary objective is to determine the overall response to pembrolizumab for patients with
residual disease following radiation with or without systemic therapy for squamous cell
carcinoma of the head and neck.

Hypothesis: The use of pembrolizumab in patients with residual disease following radiation
with or without systemic therapy will lead to an enhanced overall response rate due to
treatment-related priming of the immune response.

Inclusion Criteria:

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

2. Be => 18 years of age on day of signing informed consent.

3. Biopsy proven residual disease.

4. Be willing to provide tissue from a newly obtained core 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 1 and following completion of RT/CRT.

5. Have a performance status of 0 or 1 or 2 on the ECOG Performance Scale.

6. Demonstrate adequate organ function. Labs value need to be assessed within 14 days of
study treatment.

7. 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.

8. 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 (Reference
Section 5.7.2). Subjects of childbearing potential are those who have not been
surgically sterilized or have not been free from menses for > 1 year.

9. 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.

10. Patients must have a history of Stage I-IVB SCC of the head and neck arising from the
oral cavity, oropharynx, nasopharynx, larynx, or hypopharynx and must have been
treated with definitive intent radiation (with or without systemic therapy)

11. Patients must be at least 6 weeks (42 days) and no more than 24 weeks (168 days) from
completion of radiation with or without systemic therapy at the time of biopsy
confirming residual disease. Patients must receive the first dose of study medication
no more than 28 weeks following completion of radiation.

12. Patients must have pathological evidence of persistent lymph node disease or
persistent disease at the primary tumor site with viable tumor cells confirmed by a
biopsy within 24 weeks of study treatment and no evidence of metastatic disease
following primary radiation with or without systemic therapy confirmed by a CT scan
within 4 weeks of study treatment. If a biopsy confirming residual disease has not
been performed, this can be performed after obtaining consent during the screening
procedures.

13. Persistent lymph node disease with viable tumor cells will be determined by the
histological determination of tumor viability.

14. All persistent disease must have received at least 66 Gy in 1.8-2Gy fractions of
radiotherapy to the area of residual disease (or a biologically equivalent dose given
by the linear quadratic equation: biologically equivalent dose (BED) = nd (1 + d/(
α/β), where n is the number of fractions, d dose per fraction and the α/β ratio for
tumor is 10. Previous radiation records will be obtained to confirm adequate dosing.

Exclusion Criteria:

1. 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.

2. Has a diagnosis of immunodeficiency or is receiving supraphysiologic doses of systemic
steroid therapy or any other form of immunosuppressive therapy within 7 days prior to
the first dose of trial treatment. A physiologic dose of steroids is defined as up to
10mg of prednisone daily (or its equivalent).

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

4. Hypersensitivity to pembrolizumab or any of its excipients.

5. 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 acute,
non-hematological adverse events due to agents administered more than 4 weeks earlier,
unless otherwise approved by the Principal Investigator.

- Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤
Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any
grade xerostomia, and any grade dysgeusia, are an exception to this criterion and
may qualify for the study. Also please note that the presence of a feeding tube
to aid with nutrition does not disqualify patients from study.

- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.

6. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to the first protocol treatment or who has not recovered (i.e., ≤
Grade 1 or at baseline) from acute, non-hematological adverse events due to a
previously administered agent, unless otherwise approved by the Principal
Investigator.

- Note: Subjects with ≤ Grade 2 neuropathy, any grade dysphagia, ≤ Grade 2 pain, ≤
Grade 2 weight loss, any grade hyperpigmentation of skin, any grade fatigue, any
grade xerostomia, and any grade dysgeusia, are an exception to this criterion and
may qualify for the study. Also please note that the presence of a feeding tube
to aid with nutrition does not disqualify patients from study.

- Note: If subject received major surgery, they must have recovered adequately from
the toxicity and/or complications from the intervention prior to starting
therapy.

7. 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.

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

9. 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.

10. Has known history of non-infectious pneumonitis that required steroids, or current
pneumonitis.

11. Has an active infection requiring systemic therapy.

12. 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.

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

14. 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.

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

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

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

18. Has received a live vaccine within 30 days of the first protocol treatment. 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.

19. Any patient receiving adjuvant systemic therapy following the completion of radiation
therapy is ineligible.

20. Any patient with evidence of distant metastatic disease on a CT within 4 weeks of
treatment is ineligible.

21. Evidence of interstitial lung disease.