Futibatinib and Pembrolizumab for Treatment of Advanced or Metastatic FGF19 Positive BCLC Stage A, B, or C Liver Cancer

Inclusion Criteria

• Age >= 18 years
• Adequate tissue for FGF19 testing by ribonucleic acid (mRNA) or immunohistochemistry (IHC)
• Disease characteristics:
• Radiologically or pathologically confirmed hepatocellular carcinoma (HCC) that is not eligible for curative resection, transplantation, or ablative therapies
• NOTE: Prior radiation, chemoembolization, radioembolization, or other local ablative therapies or hepatic resection are permitted
• Measurable disease by any imaging modality as defined by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria in at least one site not previously treated with radiation or liver directed therapy (including bland, chemo- or radio-embolization, or ablation)
• NOTE: Tumor lesions in a previously irradiated area are not considered measurable disease; disease that is measurable by physical examination only is not eligible
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0, 1 or 2
• Absolute neutrophil count (ANC) >= 1500/mm^3 (= = 8.0 g/dL (= = 75,000/mm^3 (= = 2.5 g/dL (= = 40 ml/min using the Cockcroft-Gault formula (= 480 msec
• NOTE: Patients with an atrioventricular pacemaker or other condition (for example, right bundle branch block) that renders the QT measurement invalid are an exception and the criterion does not apply
• Co-morbid systemic illnesses or other severe concurrent disease which, in the judgment of the investigator, would make the patient inappropriate for entry into this study or interfere significantly with the proper assessment of safety and toxicity of the prescribed regimens
• Receiving any other investigational agent which would be considered as a treatment for the primary neoplasm
• History or risk of autoimmune disease, including, but not limited to, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjogren's syndrome, Guillain-Barre syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis. Notes:
• Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone are eligible.
• Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen are eligible.
• Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
• Must not have ocular manifestations
• Rash must cover less than 10% of body surface area (BSA)
• Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, flucinolone 0.01%, desonide 0.05%, aclometasone dipropionate 0.05%)
• No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
• Known active human immunodeficiency virus (HIV) infection (defined as patients who are not on anti-retroviral treatment and have detectable viral load and CD4+ 7 days to be eligible. Patient may be eligible if fever is present and infection has been ruled out or fever is related to tumor
• Psychiatric illness/social situations that would limit compliance with study requirements
• Clinically significant or uncontrolled cardiac disease, including unstable angina, acute myocardial infarction within 6 months from day 1 of study treatment administration, New York Heart Association class III and IV congestive heart failure, and uncontrolled arrhythmia
• NOTE: Participants with pacemaker or with atrial fibrillation and well controlled heart rate are allowed
• Other active malignancy <6 months prior to pre-registration
• EXCEPTIONS: Non-melanotic skin cancer, papillary thyroid cancer, or carcinoma-in-situ o