• Fully-informed written consent and locally required authorization (European Union \[EU\]: General Data Privacy Regulation (GDPR)) obtained from the patient prior to performing any protocol-related procedures, including screening evaluations.

• Age ≥ 18 years.

• Histologically documented diagnosis of locally-advanced OR limited metasized intrahepatic BTC not amenable to curative treatment (tumor resection or ablation), specified as

‣ Tumor being confined to the liver or

⁃ In case of presence of extrahepatic lesions, metastasis must be stable AND of limited extent\* AND patient must have a potential benefit from study participation in comparison to standard of care systemic therapy per local tumor board evaluation.

‣ \*Limited extent is defined in this protocol as presence of

∙ EITHER ≤3 malignant extrahepatic lymph nodes (short axis diameter ≥3cm)

∙ OR metastatic lesions in one organ other than liver (if only single lesion is present diameter MUST be \< 3cm; if up to 3 lesions in one organ each lesion MUST be ≤ 1cm).

∙ Presence of peritoneal or brain metastatsis excludes patients from study participation (see exclusion criterion #4)

⁃ Tumor tissue (block or at least 4 slides) is available for translational research.

• Patients with prior chemotherapy and/or immunotherapy can be enrolled if ONE of the following criteria is met:

‣ Capecitabin or gemcitabine+cisplatin in the adjuvant setting

⁃ Experienced progressive disease under gemcitabine+cisplatin therapy in the advanced setting

⁃ Stable disease after 3 months of gemcitabine+cisplatin treatment

⁃ Experienced progressive disease under durvalumab+ gemcitabine+cisplatin in first line treatment

⁃ Experienced progressive disease under pembrolizumab+ gemcitabine+cisplatin in first line treatment

• Has been considered candidate for standard-of-care Y-90 SIRT therapy per Investigator decision and after prior consultation with the tumor board if available at site and does not display contraindications against SIRT.

• Contraindications against SIRT would be

⁃ hepatic tumor load \> 50%

⁃ any Gastrointestinal deposition that cannot be corrected via angiographic techniques

⁃ irreversibly elevated serum bilirubin

⁃ renal insufficiency

⁃ increased pulmonary shunt fraction being able to deliver \> 16.5 mCi to the lungs

⁃ gastrointestinal ulceration

⁃ hepatic dysfunction

⁃ biliary complications

⁃ portal hypertension

⁃ vascular injury and lymphopenia.

• Performance status (PS) ≤ 1 (ECOG scale).

• Body weight \>30 kg

• At least one measurable site of disease as defined by RECIST 1.1 criteria.

• Adequate bone marrow and renal function

⁃ Adequate hepatic function (with stenting for any obstruction, if required)

⁃ Female patients with reproductive potential must have a negative urine or serum pregnancy test within 7 days prior to start of trial.

⁃ 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 patient is willing and able to comply with the protocol for the duration of the study, including hospital visits for treatment and scheduled follow-up visits and examinations.

⁃ Must have a life expectancy of at least 12 weeks.

⁃ If patient has concurrent Hepatitis B virus (HBV) or Hepatitis C virus (HCV) infection, meets the following criteria:

∙ Patients with HBV or HCV infection should be monitored for viral levels during study participation.

‣ Patients with detectable hepatitis B surface antigen (HBsAg) or detectable HBV DNA should have HBV DNA \< 100 IU/ml and should be managed per local treatment guidelines.

• Controlled (treated) hepatitis B subjects will be allowed if they started treatment at the time point of enrollment into the study by the latest and treatment is continued during study participation and for ≥ 6 months after end of study treatment.

• \- HCV patients with advanced BTC are mostly not treated for their HCV infection. However, patients treated for HCV are considered suitable for inclusion if antiviral therapy has been completed ≥ 30 days prior to first administration of study drug.