Durvalumab + Tremelimumab ± Paclitaxel in Advanced BTC After Platinum Chemotherapy.

Inclusion Criteria: 1. Written informed consent obtained from the patient prior to performing any protocol-related procedures, including screening evaluations. 2. Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up. 3. Histologically or cytologically proven BTC (extrahepatic CCA, intrahepatic CCA, or gallbladder carcinoma). 4. Failure (documented progression or toxicity) of previous platinum-based (cisplatin or oxaliplatin) therapy (e.g. GEMCIS, GEMOX, FOLFIRINOX) Note: a maximum of 1 previous chemotherapy line is allowed; maintenance therapy with chemotherapy or targeted agent, except immunotherapy, will be permitted. 5. Age ≥ 18 years at the time of study entry. 6. ECOG PS 0-1. 7. Recurrent or advanced disease not amenable to surgery, radiation, or combined modality therapy with curative intent (previous resection of primary tumor allowed). 8. Measurable or evaluable (radiologically detectable disease which does not fulfill RECIST criteria for measurable disease) lesions according to RECIST v1.1 criteria (CT-scan \< 3 weeks). 9. Have tissue from an archival tissue sample that has been identified and confirmed as available for study, or newly obtained core or excisional biopsy of a tumor lesion. 10. Adequate organ function, as defined by the following: * Serum aspartate aminotransferase (AST) and serum alanine aminotransferase (ALT) \< 3 x upper limit of normal (ULN) * Total serum bilirubin \< 1.5 ULN * Prothrombin ratio \> 70% * Serum albumin ≥ 28 g/L * Hemoglobin ≥ 9.0 g/dl * White blood cell count (WBC) ≥ 3,000/μL * Absolute neutrophil count (ANC) ≥ 1,500/μL * Platelets ≥ 100,000/μL * Serum creatinine ≤ 1.5 ULN or creatinine clearance \> 50 mL/min (MDRD). 11. Body weight \> 40 kg. 12. Any other prior therapy directed at the malignant tumor, including chemotherapy, chemoembolization therapy, molecular targeted therapy (including antiangiogenics), and radiotherapy, must be discontinued at least 2 weeks prior to registration and at least 3 weeks before day 1 on trial. 13. Life expectancy ≥ 3 months. 14. Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply: Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy). Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \> 1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). Women participants of childbearing potential must have a negative serum pregnancy test within the 7 days prior to the first treatment administration. Both women participants of childbearing potential and men participants who are sexually active with women of childbearing potential must agree to use a reliable method of birth control (i.e. pregnancy rate \< 1% per year); women of childbearing potential will be instructed to adhere to contraception for a period of 180 days after the last dose of durvalumab and tremelimumab or 90 days after the last dose of durvalumab monotherapy or 6 months after the last dose of paclitaxel. Men participants who are sexually active with women of childbearing potential will be instructed to adhere to contraception and must refrain from sperm donation for a period of 180 days after the last dose of durvalumab and tremelimumab or 90 days after the last dose of durvalumab monotherapy or 6 months after the last dose of paclitaxel. 15. Registration in a national health care system (PUMA included). Exclusion Criteria: 1. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site). 2. Concurrent enrolment in another clinical study, unless it is an observational (non-interventional) or supportive care clinical study or during the follow-up period of an interventional study. 3. Receipt of the last dose of anticancer therapy (investigational product, chemotherapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies) ≤ 21 days prior to the first dose of study drug. If sufficient wash-out time has not occurred due to the schedule or pharmacokinetics properties of an agent, a longer wash-out period will be required, as agreed by AstraZeneca/MedImmune and the investigator. 4. Mixed histology (hepatocholangiocarcinoma). 5. Extensive tumor massively replacing both entire lobes. 6. Obstructive jaundice (bilirubin \> 1.5 ULN) without adequate biliary drainage. 7. 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 excluded * 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. 8. History of allogenic organ transplantation. 9. Any systemic steroid therapy (\> 10 mg daily dose of prednisone or equivalent) whatever the duration of this corticotherapy Note: The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication). 10. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and TB testing in line with local practice), hepatitis B (known positive HBV surface antigen (HBsAg) result), hepatitis C, or human immunodeficiency virus (positive HIV 1/2 antibodies) Note: Patients with past HBV infection or resolved HBV infection (defined as having a negative HBsAg test and a positive hepatitis B core antigen \[HBc\] antibody test) are eligible. Note: Patients positive for HCV antibody are eligible only if polymerase chain reaction testing is negative for HCV ribonucleic acid (RNA). 11. Diagnosis of any second malignancy within the last 5 years, except for adequately treated basal cell or squamous cell skin cancer, or in situ carcinoma of the cervix uteri. 12. Prior treatment with taxane or any immune ICI, including durvalumab and tremelimumab or any other anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody. 13. Known active central nervous system metastases and/or carcinomatous meningitis; patients with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least 4 weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids \> 10 mg/day of prednisone or equivalent for at least 14 days prior to trial treatment. 14. Uncontrolled massive pleural effusion or massive ascites. 15. Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc\]), that has required systemic treatment (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs) Note: Patients with vitiligo, alopecia, or any chronic skin condition that does not require systemic therapy are exception to this criterion. Note: History of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible. Note: Controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible. 16. Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations 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. 17. Live vaccine administration within 30 days prior to the first dose of study treatment Note: Patients, if enrolled, should not receive live vaccine whilst receiving investigational product and up to 30 days after the last dose of investigational product. 18. Known or suspected allergy or hypersensitivity to any of the study drugs or any of the study drug excipients (taxane, durvalumab, or tremelimumab). 19. Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms. 20. History or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with participation for the full duration of the trial, or is not in the best interest of the participant, in the opinion of the treating investigator. 21. Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug. 22. Major surgical procedure (as defined by the Investigator) within 28 days prior to the first dose of investigational product Note: Local surgery of isolated lesions for palliative intent is acceptable. 23. Pregnancy/lactation. 24. Tutelage or guardianship.