A Phase 1 Study of BLU-554 in Patients With Hepatocellular Carcinoma

This is a Phase 1, open-label, first-in-human (FIH) study designed to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary antineoplastic activity of BLU- 554 administered orally in patients with FGF19 IHC+ hepatocellular carcinoma (HCC). The study consists of 3 parts, a dose-escalation part (Part 1), an expansion part (Part 2) exploring a once daily (qd) dosing schedule at the recommended Phase 2 dose (RP2D), and a Part 3 expansion of the qd dosing schedule at the RP2D in TKI naive patients.

Inclusion Criteria

• Confirmed diagnosis of HCC by histological examination or by non-invasive criteria according to European Association for the Study of the Liver (EASL) or American Association for the Study of Liver Disease (AASLD) guidelines (Part 1, 2 and 3).
• For Part 1 and 2, the patient has unresectable disease and has been previously treated with sorafenib, has declined treatment with sorafenib, or does not have access to sorafenib.
• For Part 3, the patient has not received prior treatment with a TKI.
• Child-Pugh class A with no clinically apparent ascites
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1
• For Part 1, willing to provide archived tumor tissue (if available) and willing to undergo pre- and on-treatment tumor biopsy (if considered safe and medically feasible by the treating investigator)
• For Part 2 and 3, all patients must have an FGF19 IHC result available. Only FGF19 IHC+ HCC patients will be eligible for Part 3.

Exclusion Criteria

• Central nervous system metastases
• Platelet count <75,000/mL
• Absolute neutrophil count <1000/mL
• Hemoglobin <8 g/dL
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >5x the upper limit of normal (ULN)
• Total bilirubin >2.5 mg/dL
• International normalized ratio (INR) >2.3 or prothrombin time (PT) >6 seconds above control
• Estimated (Cockroft-Gault formula) or measured creatinine clearance <40 mL/min

Lead Organization
Blueprint Medicines Corporation