• Ability to comprehend and willingness to sign a written ICF for the study

• Male and female participants at least 18 years of age at the time of signing the ICF

• Histologically or cytologically confirmed locally advanced unresectable or metastatic intrahepatic cholangiocarcinoma; at least one intrahepatic lesion must be present

• Radiographically measurable or evaluable disease by CT or MRI per RECIST v1.1 criteria

• ECOG performance status ≤1

• Body weight \>30 kg

• Must have a life expectancy of at least 12 weeks

• Participants must have adequate marrow function as defined below:

‣ Hemoglobin ≥9.0 g/dL

⁃ Absolute neutrophil count (ANC) ≥1.0 × 109 /L

⁃ Platelet count ≥75 × 109/L

• Participants must have adequate renal function as defined below:

‣ Serum creatinine ≤ 1.5 mg/dL OR

⁃ Measured creatinine clearance (CL) \>40 mL/min or Calculated creatinine CL\>40 mL/min by the Cockcroft-Gault formula (Cockcroft and Gault 1976) or by 24-hour urine collection for determination of creatinine clearance

• Participants must have adequate hepatic function as defined below:

‣ Bilirubin ≤1.5 x ULN

⁃ ALT ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤5x ULN

⁃ AST ≤ 2.5 x ULN unless liver metastases are present, in which case it must be ≤5x ULN

⁃ This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), who will be allowed only in consultation with their physician

⁃ No known history of active HBV or HCV infection.

• Note: Participants with Hepatitis C who have been clinically cured, defined as persistent absence of Hepatitis C RNA detected by polymerase chain reaction (PCR) test in serum 12 weeks after completing antiviral treatment, are eligible for this study

∙ Note: Participants with a history of Hepatitis B infection that are currently on viral suppressive therapy are eligible for enrollment

• Adequate coagulation studies as demonstrated by prothrombin (PT) and partial thromboplastin (PTT) time within normal limits (\</= 1.5 x ULN) in the absence of anticoagulation medication. Participants receiving anticoagulation may be approved by sponsor

• Participants with known human immunodeficiency virus (HIV) on effective highly-active antiretroviral therapy (HAART) with undetectable viral load within 6 months are eligible for this trial, so long as the following criteria are met:

‣ HAART does not interact with or have overlapping toxicities with study medication, per discretion of the treating provider

⁃ CD4 count is ≥350 cells/uL, viral load is undetectable, and not taking prohibited cytochrome (CYP)-interacting medications

⁃ Probable long-term survival with HIV if cancer were not present

⁃ Stable on a HAART regimen for ≥4 weeks and willing to adhere to their HAART regimen with minimal overlapping toxicity and drug-drug interactions with the experimental agents in this study

⁃ HIV is not multi-drug resistant

⁃ Taking medication and/or receiving antiretroviral therapy that does not interact or have overlapping toxicities with the study medication