| Eligibility |
Inclusion Criteria:
1. Be willing and able to provide written informed consent/assent for the trial.
2. Be more than 20 years of age on day of signing informed consent.
3. Have a performance status of 0 or 1 on the ECOG Performance Scale
4. Demonstrate adequate organ function as defined in Table 2
- 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 calculateda 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
- Albumin >2.5 mg/dL
- 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 therapyas long as PT or PTT is within therapeutic range of intended
use of anticoagulants aCreatinine clearance should be calculated per
institutional standard.
5. Histology proven nasopharyngeal carcinoma. Biopsy at nasopharynx is mandatory.
6. Completing radiotherapy more than 66Gy (curative intent radiotherapy)
7. Detectable plasma EBV DNA: it is defined by the following criteria:
1. The first test of plasma EBV DNA: 6-8 weeks after the last dose of radiotherapy.
2. If the first test of plasma EBV DNA is detectable:
- Within the "linear dynamic range": eligible by one single EBV DNA testing
- Lower than the "linear dynamic range": it should be repeated within 2-4
weeks after the report day of first test of plasma EBV DNA. If both results
are detectable, the patient is eligible
- *The "linear dynamic range" is defined as the highest to the lowest
quantifiable copy number established by means of a calibration curve (MIQE
guidelines, 7.4.2 section, Clin Chem. 2009;55(4):611-22)
8. No detectable residual disease or distant metastases after imaging studies: The
following examinations should be completed within 28 days after the report day of
detectable plasma EBV DNA. If a repeated test of plasma EBV DNA is necessary by
criteria 7, the following examination should be completed within 28 days after the
report day of the repeated plasma EBV DNA test.
1. For locally residual disease, head and neck MRI should be completed. For patients
who cannot take MRI, CT scan with and without contrast should be completed.
2. For distant metastases, one of the following studies should be completed.
- Whole body PET-CT scan (if the modality is available)
- CT scan with and without contrast of chest and abdomen, and bone scan
9. Female subject of childbearing potential should have a negative urine or serum
pregnancy test. If the urine test is positive or cannot be confirmed as negative, a
serum pregnancy test will be required.
10. Female subjects of childbearing potential (Section 5.5.2) must be willing to use an
adequate method of contraception as outlined in Section 5.5.2 - 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.
11. Male subjects of childbearing potential (Section 5.5.2) must agree to use an adequate
method of contraception as outlined in Section 5.5.2- 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. Other malignancies diagnosed before or concurrently with the diagnosis of NPC.
2. Take chemotherapy or other anti-cancer agents after curative chemoradiation.
3. Documented residual / recurrent local disease or distant metastases after
completing chemoradiation.
4. Plasma EBV DNA is un-detectable.
5. Unresolved grade 2 or more acute toxicities related to chemoradiation
6. 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.
7. Hypersensitivity to pembrolizumab or any of its excipients.
8. 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. Topical or
inhaled steroids is not considered as systemic treatment.
9. Has known history of pneumonitis requiring steroids, or any evidence of active,
non-infectious pneumonitis
10. Has an active infection requiring systemic therapy 14 days before signing
informed consent.
11. 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.
12. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
13. 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.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
15. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
16. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA
[qualitative] is detected).
17. 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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