MK-3475 Immunotherapy in Endometrial Carcinoma
MK-3475 Immunotherapy in Endometrial Carcinoma
Due to the high expression of PD-L1 in endometrial cancers as well as in ovarian cancers
 which are molecularly similar to uterine serous cancers, using pembrolizumab should be
 beneficial in this patient population. Since the investigators are able to get a
 pre-treatment research- related endometrial biopsy as well as the surgical specimen post two
 cycles of pembrolizumab, the investigators will be able to evaluate the mechanism of action
 of this drug on the endometrial cancer tumor environment.
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.