MK-3475 Immunotherapy in Endometrial Carcinoma

Inclusion Criteria:

- Diagnosis of FIGO grade 3 endometrioid cancer, serous, clear cell, or mixed high grade
endometrial cancer with confirmation on research-related endometrial biopsy.

- Radiographically confirmed endometrial adenocarcinoma of stages III-IV requiring
adjuvant therapy. If stage III disease is suspected, there should be multiple pelvic
and/or lymph nodes involved.

- Measurable disease defined as lesions that can be accurately measured in at least one
dimension (longest diameter to be recorded) as >10 mm with CT scan, as >20 mm by chest
x-ray, or >10 mm with calipers by clinical exam by RECIST 1.1.

- Treatment plan must include primary site biopsy followed by resection of the primary
tumor site and any metastatic sites at time of surgery.

- At least 18 years of age.

- GOG performance status ≤ 2

- Normal bone marrow and organ function as defined below:

- Absolute neutrophil count ≥ 1,500/mcl

- Platelets ≥ 100,000/mcl

- Hemoglobin ≥ 9 g/dL

- Total bilirubin ≤ 1.5 x IULN OR direct bilirubin ≤ IULN for patients with total
bilirubin > 1.5 x IULN

- AST(SGOT)/ALT(SGPT) ≤ 2.5 x IULN (or ≤ 5 x IULN for patients with liver
metastases)

- Serum creatinine ≤ 1.5 x IULN OR creatinine clearance by Cockcroft-Gault ≥ 60
mL/min/1.73 m2 for patients with creatinine levels > 1.5 x IULN

- INR or PT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long
as INR or PTT is within therapeutic range of intended use of anticoagulants

- aPTT ≤ 1.5 x IULN unless patient is receiving anticoagulant therapy as long as
INR or PTT is within therapeutic range of intended use of anticoagulants

- Sexually active women of childbearing potential must agree to contraceptive methods as
described by the protocol prior to study entry, for the duration of pre-operative
study participation and until definitive hysterectomy/bilateral salpingo-oophorectomy.
Should a woman become pregnant or suspect she is pregnant while participating in this
study, she must inform her treating physician immediately.

- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).

Exclusion Criteria:

- FIGO grade 1 or 2 endometrioid cancer.

- Radiographic imaging demonstrating uterine cancer that is probably stage I or II.

- Prior treatment for endometrial cancer.

- Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.

- Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to first dose of
MK-3475 or has not recovered (i.e., to ≤ grade 1 or baseline) from adverse events due
to agents administered more than 4 weeks earlier.

- Prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2
weeks prior to the first dose of MK-3475 or has not recovered (i.e., to ≤ grade 1 or
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 a subject received major surgery, she must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.

- Received a live vaccine within 30 days prior to the first dose of MK-3475. Examples of
live vaccines include, but are not limited to, the following: measles, mumps, rubella,
varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG),
and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed
virus vaccines and are allowed; however, intranasal influenza vaccines (e.g. FluMist)
are live attenuated vaccines and are not allowed.

- A history of other malignancy ≤ 5 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only.

- Known active central nervous system 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 4 weeks prior to the
first dose of MK-3475 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.

- Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in
dosing exceeding 10 mg daily of prednisone or equivalent) or any other form of
immunosuppressive therapy within 7 days prior to the first dose of MK-3475.

- Currently receiving any other investigational agents or has participated in a study of
an investigational agent or using an investigational device within 4 weeks of the
first dose of MK-3475.

- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to MK-3475 or other agents used in the study.

- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection requiring systemic therapy, symptomatic congestive heart failure, unstable
angina pectoris, cardiac arrhythmia, immunosuppression, autoimmune conditions,
underlying pulmonary disease, or psychiatric illness/social situations that would
limit compliance with study requirements.

- Has an 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 (e.g., 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.

- Pregnant and/or breastfeeding. Patient must have a negative serum or urine pregnancy
test within 72 hours of study entry.

- Known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg] reactive)
or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected).

- Known history of HIV (HIV 1/2 antibodies).

- Known history of active TB.