Trial of Pembrolizumab in Cancer of Unknown Primary

Inclusion Criteria

• Be willing and able to provide written informed consent/assent for the trial.
• Be 18 years of age on day of signing informed consent.
• Have measurable disease based on RECIST 1.1
• Be willing to provide consent for archival tumour (in the form of formalin fixed paraffin embedded (FFPE) block) or fresh tumour material (if judged technically feasible by radiologist is mandatory for diagnosis and biomarker analysis.
• Have a performance status of 0-2 on the ECOG Performance Scale.
• Cohort 1 - have had at least one prior line / regimen of chemotherapy appropriate for CUP (at least 2 cycles), have not had a RECIST response to first-line chemotherapy, or are progressing after an initial response, or are treatment intolerant to first-line chemotherapy, due to unacceptable toxicity.

Cohort 2 - be chemo-naive for CUP*

*Previous chemotherapy for other cancers is allowed

• Adequate organ and bone marrow function (all screening tests should be performed within 10 days of treatment initiation):
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L
• Platelets ≥ 100 x 109/L
• Haemoglobin ≥ 9 g/dL (≥90 g/L) without transfusion or Erythropoietin (EPO) dependency (within 7 days of assessment)
• Serum creatinine ≤ 1.5 x Upper Limit of Normal (ULN) or Creatinine clearance* ≥ 60 mL/min for patients with creatinine levels > 1.5 x ULN
• Creatinine clearance should be calculated per institutional standard
• Serum total bilirubin ≤ 1.5 x ULN or direct bilirubin ≤ ULN for patients with total bilirubin levels >1.5 ULN
• Aspartate aminotransferase [AST] ≤ 2.5 x ULN (< 5 x ULN if liver metastases are present)
• Alanine aminotransferase [ALT]) ≤ 2.5 x ULN (< 5 x ULN if liver metastases are present)
• Albumin ≥ 2.5g/dL
• International Normalized Ratio (INR) or Prothrombin Time (PT) ≤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)
• 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)
• Female subject of childbearing potential should have a mandatory negative serum pregnancy within 72 hours prior to receiving the first dose of study medication.
• Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 6.9.2 - 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.

• Male subjects of childbearing potential must agree to use an adequate method of contraception as outlined in Section 6.9.2 - 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

• 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.
• 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 Bacillus Tuberculosis (TB)
• 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 eve