Pembrolizumab in Combination With Lenvatinib in Patients With Advanced Biliary Tract Carcinoma

Inclusion Criteria:

* Patients must meet the following criteria in order to be eligible to participate in the study:

  1. Unresectable or metastatic, histologically-confirmed advanced BTC (excluding periampullary cancer)
  2. Failed standard systemic therapy for advanced BTC due to progression of disease or toxicity
  3. Measurable disease
  4. Prior chemoembolization, radiofrequency ablation, or radiation to the liver is allowed as long as the patient has measurable disease outside the chemoembolization or radiation area or measurable progression at the site of chemoembolization or radiation
  5. ECOG Performance status ≤ 1
  6. Life expectancy \> 3 months
  7. Adequate renal function as defined by Cr ≤ 1.5 upper limit of normal (ULN) or glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2
  8. Adequate hepatic function as defined by bilirubin ≤ 2.5 x ULN and alanine transaminase (ALT) and aspartate aminotransferase (AST) ≤ 5x ULN
  9. Adequate bone marrow reserve as evidenced by ANC \> 1500/mcl, Plts \>75,000/mcl, Hgb ≥ 9.0g/dl
  10. Prothrombin time / Partial thromboplastin time (PT/PTT) \<1.5x ULN
  11. Urine Protein: Creatinine ratio of \<1, if protein is \> 2+ on urinalysis
  12. Age ≥ 18 years
  13. Participants with past or ongoing hepatitis C virus (HCV) infection are eligible for the study. Treated participants must have completed their treatment at least 1 month prior to starting study intervention. Untreated or incompletely treated HCV participants may initiate anti-viral therapy for HCV if liver function remains stable for at least 3 months on study intervention
  14. Participants with controlled hepatitis B are eligible for the study, as long as they meet the following criteria:

      Participants with chronic hepatitis B virus (HBV) infection, defined as HBsAg positive and/or detectable HBV DNA, must be given antiviral therapy for HBV for at least 4 weeks prior to the first dose of study intervention and HBV viral load must be less than 100 IU/ml. prior to the first dose of study treatment. Participants on active HBV therapy with viral loads under 100 IU/ml. should stay on the same therapy throughout study intervention. Antiviral therapy after completion of study intervention should follow local guidelines.
  15. Participants with clinically resolved HBV infection, defined as HBsAg negative and anti-hepatitis B core antigen (HBc) positive, and who have an undetectable HBV viral load at screening should be checked every 6 weeks for HBV viral load and treated for HBV if viral load is over 100 IU/ml. Antiviral therapy after completion of study intervention should follow local guidelines.

Exclusion Criteria:

* Patients who exhibit any of the following conditions at screening will not be eligible to be enrolled to the study:

  1. Prior treatment with other VEGF-R directed therapies
  2. Periampullary cancer
  3. Major surgery or radiation within the 4 weeks prior to enrollment; is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of registration. The treated patients must recover from their relevant treatment(i.e. to≤1 grade or baseline) and from any AEs caused by any previous treatment
  4. Uncontrolled hypertension defined by systolic blood pressure (SBP)\>150 or diastolic blood pressure (DBP)\>90 despite titration of anti-hypertensive medications
  5. Active, known or suspected autoimmune disease
  6. Congestive heart failure or symptomatic coronary artery disease within 3 months prior to enrollment
  7. Cerebrovascular accident within prior 6 months
  8. Clinically significant hemorrhage, bleeding event, or thromboembolic disease within six months
  9. History of bowel perforation
  10. History of (non-infectious) pneumonitis that required steroids or currently has pneumonitis
  11. Known history of HIV infection
  12. Severely impaired lung function or history of interstitial lung disease
  13. Concurrent malignancy (other than adequately treated non-melanoma skin cancer, superficial transitional cell carcinoma of the bladder, and cervical CIS) diagnosed within the past 5 years or any currently active malignancy
  14. Positive serum pregnancy test within 72 hours of first dosing of study treatment
  15. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject's participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator