| Eligibility |
Inclusion Criteria:
- In order to be eligible for participation in this trial, the subject must:
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be above 18 years of age on day of signing informed consent.
3. Have measurable disease based on RECIST 1.1.
4. 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.
5. Have a performance status of 0 to 2 on the ECOG Performance Scale.
6. Demonstrate adequate organ function as defined in Table 1, all screening labs
should be performed within 10 days of treatment initiation.
Table 1 Adequate Organ Function Laboratory Values System Laboratory Value
Hematological Absolute neutrophil count (ANC) =1,500 /mcL Platelets =100,000 /
mcL Hemoglobin =9 g/dL or =5.6 mmol/L without transfusion or EPO dependency
(within 7 days of assessment) Renal Serum creatinine OR Measured or calculated
creatinine clearance (GFR can also be used in place of creatinine or CrCl) =1.5 X
upper limit of normal (ULN) OR =60 mL/min for subject with creatinine levels >
1.5 X institutional ULN Hepatic Serum total bilirubin = 1.5 X ULN OR Direct
bilirubin = ULN for subjects with total bilirubin levels > 1.5 ULN, AST (SGOT)
and ALT (SGPT) = 2.5 X ULN OR = 5 X ULN for subjects with liver metastases
Albumin >2.5 g/L Coagulation International Normalized Ratio (INR) or Prothrombin
Time (PT) Activated Partial Thromboplastin Time (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 =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.
7. 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.
8. Female subjects of childbearing potential (Section 5.7.2) must be willing to use
an adequate method of contraception as outlined in Section 5.7.2 - 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.
9. Male subjects of childbearing potential (Section 5.7.1) must agree to use an
adequate method of contraception as outlined in Section 5.7.1- Contraception,
starting with the first dose of study therapy through 120 days after the last
dose of study therapy.
Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception
for the subject.
Exclusion Criteria:
The subject must be excluded from participating in the trial if the subject:
1. 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.
2. Have completed more than six (6) cycles of first line platinum doublet chemotherapy or
more than six (6) have elapsed from the last chemotherapy administration of the first
line chemotherapy with platinum doublet.
3. 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.
4. Has a known history of active TB (Bacillus Tuberculosis)
5. Hypersensitivity to pembrolizumab or any of its excipients.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. Has known history of, or any evidence of active, non-infectious pneumonitis.
12. Has an active infection requiring systemic therapy.
13. 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.
14. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
15. 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.
16. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
17. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
18. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
19. 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.
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