PRIMARY OBJECTIVES:
I. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on objective
response rate (ORR) as assessed by the investigator per immune related Response Evaluation
Criteria in Solid Tumors (irRECIST) in patients with recurrent ovarian cancer (ROC) whose
tumors show an immunoreactive gene expression signature.
SECONDARY OBJECTIVES:
I. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on
progression-free survival (PFS) as assessed by the investigator per irRECIST in patients with
ROC whose tumors show an immunoreactive gene expression signature.
II. To evaluate clinical anti-tumor activity of pembrolizumab monotherapy based on PFS rate
at 6, 12 and 18 months as assessed by the investigator per irRECIST in patients with ROC
whose tumors show an immunoreactive gene expression signature.
III. To evaluate and characterize the tolerability and safety profile of the study population
after being treated with pembrolizumab as monotherapy.
EXPLORATORY OBJECTIVES:
I. To assess correlations of the immunoreactive gene signature with the validated a PD-L1
immunohistochemistry (IHC) assay using Merck's proprietary 22C3 antibody and the clinical
activity observed in the study population.
OUTLINE:
Participants receive pembrolizumab intravenously (IV) on day 1. Courses repeat every 3 weeks
for up to 35 courses (2 years) in the absence of disease progression or unacceptable
toxicity.
After completion of study treatment, participants are followed up at 30 and then every 9 and
12 weeks thereafter.
Inclusion Criteria:
- Be willing and able to provide written informed consent/assent for the trial
- Have received 1-5 prior lines for treating ROC (i.e. 2-6 total prior lines counting
the front line) and must have a platinum-free interval (PFI) or a treatment-free
interval (TFI) >= 3 months based on the last regimen received
- Have measurable disease based on Response Evaluation Criteria in Solid Tumors (RECIST)
1.1
- Note: Tumor lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions
- Have a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
performance scale
- Have histologically diagnosed recurrent epithelial ovarian, fallopian or primary
peritoneal ovarian cancer
- Have provided a tumor tissue sample either collected from a newly obtained tumor
tissue biopsy or an archival tissue specimen. Subjects for whom newly obtained samples
cannot be provided (e.g. inaccessible or subject safety concern) may submit an
archived biopsy specimen. Formalin-fixed paraffin embedded (FFPE) block specimens are
preferred to 20 unstained slides. Additional samples may be requested if tumor tissue
provided is not adequate for quality and/or quantity as assessed by the central
laboratory
- Performed within 10 days of treatment initiation: absolute neutrophil count (ANC) >=
1,500/mcL
- Performed within 10 days of treatment initiation: platelets >= 100,000/mcL
- Performed within 10 days of treatment initiation: hemoglobin >= 9 g/dL or >= 5.6
mmol/L without transfusion or erythropoietin (EPO) dependency (within 7 days of
assessment)
- Performed within 10 days of treatment initiation: serum creatinine OR measured or
calculated creatinine clearance (CrCl) (glomerular filtration rate [GFR] can also be
used in place of creatinine or CrCl) =< 1.5 x upper limit of normal (ULN) OR >= 45
mL/min for subject with creatinine levels > 1.5 x institutional ULN
- Creatinine clearance should be calculated per institutional standard
- Performed within 10 days of treatment initiation: serum total bilirubin =<1.5 x ULN OR
direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Performed within 10 days of treatment initiation: aspartate aminotransferase (AST)
(serum glutamate pyruvate transaminase [SGOT]) and aspartate aminotransferase (ALT)
(serum glutamic-oxaloacetic transaminase [SGPT]) =< 2.5 x ULN OR =< 5 x ULN for
subjects with liver metastases
- 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
- Have received front line platinum-based chemotherapy (preoperative chemotherapy is
allowed)
- Female subjects of childbearing potential must be willing to use an adequate method of
contraception for the course of the study through 120 days after the last dose of
study medication
- Note: Abstinence is acceptable if this is the usual lifestyle and preferred
contraception for the subject
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 2 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
- 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 or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer
- 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 known history of, or any evidence of active, non-infectious pneumonitis
- Has an active infection requiring systemic therapy
- 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-PD-1, anti-PD-L1, or anti-PD-L2 agent
- Has a known history of human immunodeficiency virus (HIV) (HIV 1/2 antibodies)
- 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
- 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
