The purposed of this research is to study the safety and clinical activity of the combination of durvalumab and a CSF-1R inhibitor (SNDX-6352) in people with Intrahepatic Cholangiocarcinoma.

Inclusion Criteria:

• Have cytologically confirmed intrahepatic cholangiocarcinoma.
• All disease must be localized to the liver (locally advanced).
• Subjects must not be deemed surgical candidates.
• Must be a candidate for conventional transarterial chemoembolization or yttrium-90 radioembolization.
• Must have measureable disease be mRECIST. Measurable disease will be confirmed by radiological imaging (MRI, CT).
• Age ≥18 years
• Body weight > 30 kg
• Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1
• Life expectancy ≥12 weeks.
• Patient must have adequate organ function defined by the study-specified laboratory tests as per the protocol.
• Child Pugh Class A
• Measured creatinine clearance (CL) >40 mL/min or Calculated creatinine clearance CL>40 mL/min by the Cockcroft-Gault formula.
• Woman of childbearing potential must have a negative pregnancy test and follow contraceptive guidelines as defined per protocol.
• Must use acceptable form of birth control while on study.
• Men must use acceptable form of birth control while on study.
• Ability to understand and willingness to sign a written informed consent document.
• Willing and able to comply with the protocol for the duration of the study

Exclusion Criteria:

• Candidate for surgical resection
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up of an interventional study.
• Major surgery within 4 weeks prior to initiation of study treatment.
• Received the last dose of anticancer therapy ≤ 28 days prior to the first dose of study drug.
• All toxicities NCI CTCAE Grade ≥2 attributed to prior anti-cancer therapy other than alopecia, vitiligo, and neuropathy.
• Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
• History of allogenic organ transplantation.
• 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, checkpoint inhibitor-induced immune mediated reaction or Wegener syndrome [granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.]).
• Patient with uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, significant muscle disorders or psychiatric illness/social situations that would limit compliance with study requirements.
• History of known additional primary malignancies.
• History of leptomeningeal carcinomatosis.
• Brain metastases or spinal cord compression.
• History of active primary immunodeficiency.
• Infection with Tuberculosis, HIV or hepatitis B or C at screening.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of treatment.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of IP.
• Pregnant or breastfeeding women.
• Has a history of allergy to study treatments or any of its components of the study.
• Prior randomization or treatment in a previous durvalumab and/or SNDX-6532 clinical study regardless of treatment arm assignment.
• Patient has clinically significant heart disease.
• Any other sound medical, psychiatric, and/or social reason as determined by the Investigator.
• Unwilling or unable to follow the study schedule for any reason.