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

Study Overview
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Brief Summary
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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 fisogatinib (formerly known as 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.

Official Title
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A Phase 1 Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of BLU-554 in Patients With Hepatocellular Carcinoma

Conditions
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Hepatocellular Carcinoma (HCC)

Intervention / Treatment
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* Drug: Fisogatinib (BLU-554)


Participation Criteria
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Eligibility Criteria
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Key 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. Key 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fisogatinib (BLU-554)<br>Fisogatinib (BLU-554) capsules for oral administration. | Drug: Fisogatinib (BLU-554)<br> <br> * Other names: BLU-554;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose (MTD) on qd and bid schedules |  | During cycle 1 (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier | 
| Recommended Phase 2 dose of fisogatinib (BLU-554) on qd and bid schedules |  | At the end of every cycle (28 days) of treatment and will be determined by approximately 24 months after start of the study or earlier | 
| Number of patients with adverse events, serious adverse events and changes in physical findings, vital signs, clinical laboratory results and ECG findings |  | Every cycle (28 days) for approximately 24 months or earlier if patient terminates from the study | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules | Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and end of treatment (EOT) | Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) | 
| Time to maximum plasma concentration of fisogatinib (BLU-554) on qd and bid schedules | Blood samples may be taken at pre-dose, and 0.5, 1, 2, 4, 6, 8 and 24 hrs post dose on Cycle 1 Day 1 and Cycle 1 Day 15, Pre-dose of Cycle 2 to 4, Day 1 and EOT | Every cycle (28 days) up to cycle 4 and at end of treatment (approximately 24 months or earlier if patient terminates from the study) | 
| Fibroblast growth factor 19 (FGF19) status in tumor tissue |  | Cycle 2 (Day 56) | 
| Levels of FGF19 in blood and tumor samples |  | Cycle 1 (Day 28) | 
| Preliminary evidence of fisogatinib (BLU-554) antineoplastic activity |  | Screening, Day 1 of every odd numbered cycle starting with Cycle 3, End of treatment (at approximately 24 months or earlier if patient terminates from the study) and every three months post EOT | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver cancer, FGF19 gene amplification, FGF19 overexpression, FGF19 upregulation, Cyclin D1 (CCND1) gene amplification, Cyclin D1 (CCND1) copy number gain, BLU-554, FGFR4, Hepatocellular carcinoma, Liver Disease, Liver Neoplasms