Radioembolization With Tremelimumab and Durvalumab for Locally Advanced Unresectable or Oligo-Metastatic Intrahepatic Cholangiocarcinoma

PRIMARY OBJECTIVE:I. Characterize the safety of the combination of Y90 transarterial radioembolization(TARE), durvalumab and tremelimumab.SECONDARY OBJECTIVES:I. Overall efficacy of Y90 + tremelimumab + durvalumab as gauged by response rate(Modified Response Evaluation Criteria in Solid Tumors (mRECIST).II. Median progression free survival (PFS) and overall survival (OS). III. Infield andout of field objective response rate (complete response and partial response) rate(mRECIST and) in‐field and out‐of‐ field duration of response.IV. Resectability rate. V. Time to respond in treated and non treated lesions.VI. Correlatives:VIa. Circulating tumor deoxyribonucleic acid (ctDNA) monitoring per investigatordiscretion; VIb. Post‐treatment dose volume histograms will be obtained using Simplicitysoftware; VIbi. Tissue and blood banking for testing such as immunohistochemistry andTissue Digital Spatial Profiling ‐ list of biomarkers: CD68, CD 86, CD163, CSF1R ‐macrophage, M1/M2 markers, CD3 ‐ T‐cell differentiator, FoxP3, CD25, CD4 and 8 ‐ T‐celllineage, PD‐1, PD‐L1, etc. ‐ checkpoints, granzyme B ‐ cytotoxic T lymphocytes (CTL)activity. Next generation (Gen) profiling and ribonucleic acid (RNA) sequencing.Microsatellite instability (MSI)/ mismatch repair (MMR) status, tumor mutational burden(TMB).EXPLORATORY OBJECTIVES:I. Tissue and blood for predictive and prognostic biomarkers will be collected.OUTLINE: Patients are assigned to 1 of 2 arms.Arm I (COHORT I): Patients receive transarterial Y90 radioembolization and tremelimumabintravenously (IV) over 1 hour on day 1 of cycle 1 and durvalumab IV over 1 hour on day 1of each cycle. Cycles repeat every 28 days for up to 24 cycles in the absence of diseaseprogression or unacceptable toxicity. Patients also undergo mapping angiography duringscreening as well as computerized tomography (CT) and magnetic resonance imaging (MRI) orpositron emission tomography (PET)/CT during screening and on study. Patients alsoundergo blood sample collection throughout the trial and may undergo tumor biopsy duringscreening and on study.Arm II (COHORT II): Patients receive transarterial Y90 radioembolization on day 1 ofcycle 1 and receive tremelimumab IV over 1 hour on day 14 of cycle 1 and durvalumab IVover 1 hour on day 14 of each cycle. Cycles repeat every 42 days for cycle 1 and thenevery 28 days for cycles 2‐24 in the absence of disease progression or unacceptabletoxicity. Patients also undergo mapping angiography during screening, as well as CT andMRI or PET/CT during screening and on study. Patients also undergo blood samplecollection throughout the trial and may undergo tumor biopsy during screening and onstudy.Cohort III: This is a dose expansion cohort where patients are enrolled based on theefficacy and safety results from Cohorts I and II.After completion of study treatment, patients are followed up every 3 months for 2 years.