Inclusion Criteria:

• Age ≥ 18 years with body weight > 30 kg.
• Histologically or cytologically confirmed, locally advanced biliary tract tumor (intrahepatic cholangiocarcinoma) that is not amenable to resection, transplantation or thermal ablation.
• Measurable disease.
• Registration must be completed ≤ 14 days after pre-registration.
• ECOG Performance Status (PS) 0 or 1.
• The following laboratory values obtained ≤ 14 days prior to registration:
  • Hemoglobin ≥ 9.0 g/dL;
  • Absolute neutrophil count (ANC) ≥1000/mm^3;
  • Platelet count ≥ 75,000/mm^3;
  • Total bilirubin ≤ 1.5 x ULN;
  • Alanine aminotransferase (ALT) and aspartate transaminase (AST) ≤ 5 x ULN for patients with liver involvement;
  • Calculated creatinine clearance ≥ 40 ml/min using the Cockcroft-Gault formula or measured creatinine clearance > 40 ml/min;
  • International normalized ratio (INR) ≤ 1.6.
  • Note: INR prolongation due anticoagulation for prophylaxis in patients without liver cirrhosis could be exception.
• Adequate hepatic function Child Pugh A and ALBI 1 or 2.
• Patients with concurrent Hepatitis B (HBV) or Hepatitis C virus (HCV) infection should meet the following criteria:
  • Patient with HBV or should be monitored for viral levels during study participation
  • Patient with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA < 100 IU/ml and should be managed per local guidelines.
  • Controlled hepatitis B subjects will be allowed if they started treatment at the time point of enrollment in to the study by the latest and treatment is continued during study participation and for ≥ 6 months after end of study treatment.
  • Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
• Negative urine pregnancy test done prior to registration, for persons of childbearing potential only.
  • Note:  If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

Exclusion Criteria:

• Concurrent enrolment in another clinical study, unless it is an observational clinical study or during the follow up period of an interventional study.
• Any of the following prior therapies:
  • Surgery ≤ 4 weeks prior to registration;
  • Chemotherapy ≤ 12 weeks prior to registration;
  • History of > 1 prior systemic therapy for cholangiocarcinoma including that in the adjuvant setting. Any unresolved toxicity NCI CTCAE Grade ≥2 from previous anticancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria;
  • Patients with Grade ≥2 neuropathy will be evaluated on a case-by-case basis after consultation with the Study Physician;
  • Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab or tremelimumab may be included only after consultation with the Study Physician.
• History of previous locoregional therapy.
• Prior immunotherapy inclduing prior treatment with an anti-Programmed Death receptor-1 (PD-1), anti-programmed Death-1 ligand-1 (PD-L1), including durvalumab Anti-PD-L2, or anti-cytotoxic T-lymphocyte associated antigen-4 (anti-CTLA-4) antibody, including tremelimumab.
• Previous use of therapeutic cancer vaccines.
• ECOG >1.
• Unstable liver function and/ or a change in Child Pugh score during screening:
  • Child Pugh B or greater;
  • ALBI Grade > 2;
  • MELD > 10.
• Patient is unable to undergo mapping angiography or mapping angiography demonstrates tumor blood supply that does not lend itself to transarterial therapy.
• A lung shunt fraction greater than 30 Gy within a single session, or cumulative does greater than 50Gy.
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens.
• Immunocompromised patients and patients known to be HIV positive and currently receiving antiretroviral therapy.
• Active or uncontrolled autoimmune or inflammatory disorders (including Inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, Granulomatosis with polyangiitis, sarcoidosis, Grave’s disease).
• History of another primary malignancy except for:
  • Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of IP and of low potential of recurrence;
  • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease;
  • Adequately treated carcinoma in situ without evidence of disease.
• Uncontrolled intercurrent illness including, but not limited to:
  • Ongoing uncontrolled infections including tuberculosis;
  • Symptomatic congestive heart failure;
  • Unstable angina pectoris, cardiac arrhythmias and uncontrolled hypertension;
  • Chronic pulmonary disease including interstitial lung disease requiring oxygen;
  • Psychiatric illness/social situations limiting compliance that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent;
  • Chronic gastrointestinal conditions associated with diarrhea.
• History of leptomeningeal carcinomatosis.
• Presence of pulmonary metastases measuring 1 cm or greater or other extra-nodal metastatic disease.
• History of allogeneic transplantation.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab and tremelimumab. The following are exceptions to this criteria:
  • Intranasal, inhaled, topical steroids, or local steroid injections;
  • Systemic corticosteroids at physiologic doses not to exceed 10mg/day of Prednisone or its equivalent.  
• Known allergy or hypersensitivity to any of the IMPs or any of the constituents of the products.
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm.
• Pregnant or lactating female.
• Life expectancy less than 3 months.
• Intolerance to contrast agents that is refractory to medical management.
• Any other condition which the Investigator believes would make participation in the study not acceptable.
• History of primary immunodeficiency.
• Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts.
• Receipt of live attenuated vaccine within 30 days prior to the first administration of any of the IMPs and without need to receive any live attenuated vaccines during study conduct and for up to 30 days after end of Durvalumab treatment or 90 days after end of Tremelimumab treatment, respectively.