Pembrolizumab With or Without Stereotactic Body Radiation Therapy in Treating Patients With Advanced or Metastatic Merkel Cell Cancer

PRIMARY OBJECTIVES:

I. To describe the progression-free survival (PFS) of stereotactic body radiation therapy
(SBRT) + pembrolizumab (MK-3475) compared to MK-3475 alone in advanced/metastatic Merkel cell
carcinoma (MCC) patients.

SECONDARY OBJECTIVES:

I. To describe the PFS of SBRT + MK-3475 compared to MK-3475 alone across Response Evaluation
Criteria in Solid Tumors (RECIST) measurable (including both radiated and non-radiated)
cancer deposits.

II. To describe the overall response rate of SBRT + MK-3475 compared to MK-3475 alone in both
radiated and in non-radiated deposit(s).

III. To determine the PFS at 6 months of SBRT + MK-3475 compared to MK-3475 alone across all
cancerous deposits by RECIST.

IV. To determine the rate of grade > 3-4 adverse events, by organ system, by Common
Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.

V. To determine the local control of SBRT treated tumors. VI. To calculate delivered
radiation dose using cone-beam computed tomography (CT) images collected on the radiation
treatment table in the final treatment position.

CORRELATIVE SCIENCE OBJECTIVES:

I. To test the utility of CT-based radiomics to predict radiation-induced pneumonitis and
true delivered dose of SBRT based on cone beam collected imaging and diagnostic scans.

II. Biobanking for future correlative science projects.

OUTLINE: Patients are randomized to 1 of 2 groups.

GROUP I: Patients receive pembrolizumab intravenously (IV) over 30 minutes on day 1. Cycles
repeat every 21 days for up to 2 years in the absence of disease progression or unacceptable
toxicity.

GROUP II: Patients receive pembrolizumab IV over 30 minutes on day 1. Cycles repeat every 21
days for up to 2 years in the absence of disease progression or unacceptable toxicity.
Patients also undergo SBRT for 3 doses during cycle 1.

After completion of study treatment, patients are followed up every 6 months for up to 5
years.

Inclusion Criteria:

- Patients must have pathologically (histologically or cytologically) proven diagnosis
of MCC by local pathology review

- Have measurable disease based on RECIST 1.1 including at least two cancerous deposits;
at least one deposit must be RECIST measurable while at least one deposit must meet
criteria for SBRT; non-radiated tumor will be identified prior to randomization on the
protocol

- Patients must have advanced or metastatic MCC defined as evidence of distant
metastasis(es) on imaging

- Patients with locoregionally confined disease are not eligible

- No prior immunotherapy for advanced/metastatic MCC

- Patients with known or suspected central nervous system (CNS) metastases, untreated
CNS metastases, or with the CNS as the only site of disease are excluded; however,
subjects with controlled brain metastases will be allowed to enroll; controlled brain
metastases are defined as no radiographic progression for at least 4 weeks following
radiation and/or surgical treatment (or 4 weeks of observation if no intervention is
clinically indicated), and off of steroids for at least 2 weeks, and no new or
progressive neurological signs and symptoms

- Patients having received palliative radiotherapy for extracranial metastasis(es) are
eligible as long as there are 2 cancerous deposits that have not received prior
radiation therapy (RT) and they meet the following criteria

- No prior radiation therapy (> 5 Gy) to the metastasis intended to be treated with
SBRT

- No history of the following:

- Autoimmunity requiring systemic immunosuppression within 2 years

- Patients known to be human immunodeficiency virus (HIV) positive are eligible if
they meet the following:

- CD4 counts >= 350 mm^3

- Serum HIV viral load of < 25,000 IU/ml

- No other active malignancy that the investigator determines would interfere with the
treatment and safety analysis

- Not pregnant and not nursing; therefore, for women of childbearing potential only, a
negative (if your test schedule specifically indicates a urine or serum pregnancy
test, add that information at this point) pregnancy test done =< 28 days prior to
registration is required

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Absolute neutrophil count (ANC) >= 1,500/mm^3

- Platelet count >= 100,000/mm^3

- Hemoglobin >= 9.0 g/dl

- Total bilirubin =< 2.0 mg/dl

- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 3.0 x upper limit
of normal (ULN)

- Systolic blood pressure (BP) =< 150 mg HG

- Diastolic BP =< 90 mg HG

- Albumin > 3 mg/dl

- Blood urea nitrogen (BUN) =< 30 mg/dl

- Creatinine =< 1.7 mg/dl

- The following imaging workup to document metastases within 45 days prior to study
registration are required: CT scans of the chest, abdomen and pelvis with radionuclide
bone scan OR whole body (at least skull base to midthigh) positron emission tomography
(PET)/CT