Preoperative Durvalumab, Cisplatin, Gemcitabine With or Without Futibatinib Targeted Therapy for the Treatment of Resectable Intrahepatic Cholangiocarcinoma, OPTIC Trial

PRIMARY OBJECTIVE: I. To assess the feasibility and safety of a novel treatment strategy that includes conducting next generation sequencing (NGS) on a preoperative tissue biopsy to administer prior to surgical resection. SECONDARY OBJECTIVES: I. To assess the radiological response rate (RRR) according to Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) and advanced image analysis (radiomics) in patients with resectable intrahepatic cholangiocarcinoma (IHCC). II. To assess the degree of pathologic response in the surgical specimen of patients with resectable intrahepatic cholangiocarcinoma (IHCC). III. To assess response by measuring circulating tumor DNA (CT-DNA) dynamics in the blood samples of patients with resectable intrahepatic cholangiocarcinoma (IHCC). IV. To determine the R0 resection rate post-surgery in patients with resectable intrahepatic cholangiocarcinoma (IHCC). V. To determine progression-free survival (PFS) in patients with resectable intrahepatic cholangiocarcinoma (IHCC). VI. To determine recurrence-free survival (RFS) in patients with resectable intrahepatic cholangiocarcinoma (IHCC). VII. To identify patients' overall survival (OS) rate in patients with resectable intrahepatic cholangiocarcinoma (IHCC). EXPLORATORY OBJECTIVE: I. To assess the circulating and tumor immune microenvironment in tissue and blood samples. OUTLINE: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 and cisplatin IV over 60 minutes and gemcitabine IV over 30 minutes on days 1 and 8 of one 21-day cycle in the absence of disease progression or unacceptable toxicity while awaiting for NGS results. After obtaining NGS molecular results, patients with FGFR2 fusion, rearrangement, or activating mutation are assigned to Arm A, while patients without FGFR2 fusion, rearrangement, or activating mutation are assigned to Arm B. ARM A: Patients receive futibatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo magnetic resonance imaging (MRI), computed tomography (CT) and blood sample collection throughout the trial. ARM B: Patients continue receiving durvalumab IV over 60 minutes on day 1 and cisplatin IV over 60 minutes and gemcitabine IV over 30 minutes on days 1 and 8 of each cycle. Cycles repeat every 21 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo MRI, CT and blood sample collection throughout the trial. After completion of study treatment, patients are followed up every 3 months for 3 years.