Pembrolizumab in Patients With Locally Advanced or Metastatic Skin Cancer

PRIMARY OBJECTIVE:

-To establish the response rate of pembrolizumab in metastatic cutaneous squamous cell
carcinoma.

SECONDARY OBJECTIVES:

-To determine the 6-month progression-free survival and 1 year overall survival of metastatic
cutaneous squamous cell carcinoma of the skin (cSCC) treated with pembrolizumab.

OUTLINE:

Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Courses repeat
every 3 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 8-12
weeks.

Inclusion Criteria:

- All subjects must have cutaneous squamous cell carcinoma that is not curable by
surgery or radiation; both locally advanced and metastatic squamous cell carcinoma
will be included.

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

- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
1.1.

- Be willing to provide tissue from a newly 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 1. 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 the sponsor.

- Be willing to undergo normal skin biopsy prior to initiation of treatment and after
treatment.

- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
performance scale.

- Absolute neutrophil count (ANC) ≥ 1,500/microliter (mcL)

- Platelets ≥ 100,000/mcL

- Hemoglobin ≥ 9 g/dL or ≥ 5.6 mmol/L without transfusion or erythropoietin (EPO)
dependency (within 7 days of assessment)

- Serum creatinine ≤ 1.5 X upper limit of normal (ULN) OR measured or calculated
creatinine clearance (glomerular filtration rate [GFR] can also be used in place of
creatinine or creatinine clearance [CrCl]) ≥ 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

- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and
alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) ≤ 2.5 X
ULN OR ≤ 5 X ULN for subjects with liver metastases

- Albumin ≥ 2.5 mg/dL

- International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 X ULN unless
subject is receiving anticoagulant therapy as long as PT or partial thromboplastin
time (PTT) is within therapeutic range of intended use of anticoagulants.

- Activated partial thromboplastin rime (aPTT) ≤ 1.5 X ULN unless subject is receiving
anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use
of anticoagulants.

- 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.

- 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.

- 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:

- 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.

- 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, patients with human immunodeficiency virus (HIV) adequately controlled on
antiretrovirals (undetectable viral load) and patients with chronic lymphocytic
leukemia (CLL) not requiring systemic treatment will be included; in addition,
steroids for physiologic replacement will be allowed (must be equal to or less than
10mg of prednisone/day).

- Has a known history of active TB (bacillus tuberculosis).

- Hypersensitivity to pembrolizumab or any of its excipients.

- 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.

- Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 2 weeks prior to study day 1 or who has not recovered (i.e., ≤ grade 1 or at
baseline) from adverse events due to a previously administered agent.

- Note: subjects with ≤ grade 2 neuropathy are an exception to this criterion and
may qualify for the 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.

- Has a known additional malignancy that is progressing or requires active treatment;
exceptions include basal cell carcinoma of the skin that has undergone potentially
curative therapy or in situ cervical cancer. Asymptomatic CLL, not requiring
intervention will be included as long as patients meet routine laboratory parameters
of the study as outlined above. In addition, patients who have undergone curative bone
marrow transplant and currently not requiring immunosuppression, will be allowed on
study.

- 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.

- 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.

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

- Has an active infection requiring systemic therapy; exception HIV on antiretrovirals
with negative viral load.

- 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.

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

- 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- programmed
cell death 1 ligand (PD-L)1, or anti-PD-L2 agent.

- Has known active hepatitis B (e.g., hepatitis B surface antigen [HBsAg] reactive) or
hepatitis C (e.g., hepatitis C virus [HCV] ribonucleic acid [RNA] [qualitative] is
detected).

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

- cSCC that is curable via radiation or surgery; palliative radiation is allowed as long
as measurable disease outside radiation field is present for study.