Study of Pembrolizumab and Olaparib in Bile Duct Cancer

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.
• Patients must have received 1 line of prior systemic therapy for metastatic or resectable disease (i.e. patients may have received adjuvant gemcitabine and then later platin-based therapy for recurrent metastatic disease)
• Histological confirmation of cholangiocarcinoma manifesting as either intrahepatic, extrahepatic or gallbladder cancer. Patients with ampullary cancer are excluded.
• Have measurable disease based on RECIST 1.1.
• 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-investigator. Subjects from whom a biopsy is not medically possible or safe may be enrolled on the study upon agreement from the principal investigator.
• Have a performance status of 0 or 1 on the ECOG Performance Scale.
• Demonstrate adequate organ function as defined in Table 1. All screening labs will be performed within 28 days of registration.

Table 1: Adequate Organ Function Laboratory Values System Laboratory Value Hematological Absolute neutrophil count (ANC) ≥ 1,500 /μL Platelets ≥ 100,000 / μL 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

≥ 50 mL/min for subject with creatinine levels > 1.5 x institutional ULN Hepatic Serum total bilirubin ≤ 2.0 X ULN AST (SGOT) and ALT (SGPT) ≤ 3.0 X ULN OR

≤ 5 X ULN for subjects with liver metastases 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 therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants aCreatinine clearance should be calculated per institutional standard.

• 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.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section in Appendix 3). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Exclusion Criteria

• A history of anaphylaxis to olaparib
• 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.
• A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to 1st dose of treatment (see Appendix 3). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
• Has a known history of active TB (Bacillus Tuberculosis).
• Has known hypersensitivity to pembrolizumab or any of